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Impact of Epstein-Barr virus in the clinical evolution of patients with classical Hodgkin's lymphoma in Brazil

Classical Hodgkin's Lymphoma (cHL) has been frequently associated with Epstein-Barr virus (EBV), which can be found in a latent pattern in Reed-Sternberg (RS) cells. However, the impact of the presence of EBV in RS cells and its prognosis are still controversial. We analysed the presence of EBV in RS cells and its influence in the clinical evolution of patients with cHL treated in two public hospitals in the city of São Paulo, Brazil.We selected 97 patients with cHL from 1994 to 2004. Patients were only included in this study if they had (1) >18 years, (2) negative HIV serology, (3) undergone similar chemotherapy protocols, (4) paraffin blocks available with enough material for systematic review and histological reclassification and for detection of EBV in RS cells by in situ hybridization and immunohistochemistry and (5) clinical, epidemiological and laboratorial parameters available after a thorough chart review.EBV was identified in 52.5% of the cases. Mixed cellularity (MC) subtype was more common in EBV-related tumours (25.5%) (p = 0.005). There was no difference on age, gender, stage and the presence of B symptoms between the two groups. The presence of EBV did not influence event free survival (EFS) (p = 0.38) or overall survival (OS) (p = 0.80) with a median follow-up of 80 months.We demonstrate that the prevalence of EBV-related cHL in this Brazilian population is 52.5% and, that, the presence of EBV does not change the clinical evolution and OS of patients treated with similar chemotherapy protocols. Copyright © 2010 John Wiley & Sons, Ltd.

Genetic and epigenetic changes linked to Chlamydophila psittaci-associated ocular adnexal lymphomas

No Abstract.

Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas

Richter's syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma and is mostly represented by diffuse large B-cell lymphoma (DLBCL), with a post-germinal centre (GC) phenotype, clonally related to the pre-existing CLL. RS has a very poor prognosis and its pathogenetic mechanisms are poorly understood. In order to gain additional hints in RS pathogenesis, we performed a genome-wide DNA profiling study of 13 RS phases and eight matched CLL phases using the Affymetrix Human Mapping 250K NspI SNP arrays. Individual genomic profiles were heterogeneous, with no individual lesions occurring in more than half of the cases. However, several observations suggest that MYC pathway might be involved in RS. The 13q13.3-qter region containing MIRHG1 (MIR-17-92), a cluster of microRNA interacting with c-MYC, was acquired at the time of transformation. The 13q gain was coupled with the gain of c-MYC and loss of TP53. Translocation of c-MYC was acquired at transformation in a fraction of cases and this event appeared mutually exclusive with gain of MIRHG1. MYCN, a c-MYC homologue, was also recurrently gained. By comparing RS with 48 de novo DLBCL, RS presented a significantly lower prevalence of deletions affecting the PRDM1 and TNFAIP3, genes on 6q, known to be associated with a post-GC phenotype. In conclusion, the genomic profile of RS seems to differ from what observed in de novo DLBCL and in other transformed DLBCL. Genomic lesions occurring in RS are heterogeneous suggesting the existence of different RS subsets, possibly due to different transforming mechanisms. A deregulation of MYC pathway might represent one of the main transformation events in the pathogenesis of a subset of RS clonally related to the previous CLL. Copyright © 2009 John Wiley & Sons, Ltd.

The clinical relevance of Wilms Tumour 1 (WT1) gene mutations in acute leukaemia

Recurrent genetic aberrations are important predictors of outcome in acute myeloid leukaemia (AML). Numerous novel molecular abnormalities have been identified and investigated in recent years adding to the risk stratification and prognostication of conventional karyotyping. Mutations in the Wilms Tumour 1 (WT1) gene were first described more than a decade ago but their clinical significance has only recently been evaluated. WT1 mutations occur in approximately 10% of adult AML patients at diagnosis and are most frequent in the cytogenetically normal (CN) AML subgroup. These mutations appear to confer a negative prognostic outcome by increasing the risk of relapse and death. Mutation frequency is higher in pediatric patients and also appears to confer a negative impact on relapse and survival. Herein, we discuss the importance of WT1 mutations in AML. Copyright © 2009 John Wiley & Sons, Ltd.

Silibinin can induce differentiation as well as enhance vitamin D3-induced differentiation of human AML cells ex vivo and regulates the levels of differentiation-related transcription factors

Induction of terminal differentiation is a conceptually attractive approach for the therapy of neoplastic diseases. Although vitamin D derivatives (deltanoids) can induce differentiation of AML cells in vitro, so far deltanoids have not been successfully brought to the clinic, due to the likelihood of life-threatening hypercalcemia. Here, we incubated freshly obtained blood cells from patients with AML with a plant antioxidant (PAOx), silibinin (SIL), alone or together with a deltanoid. Twenty patients with AML (all subtypes except M3) were available for this study, and in 14 (70%), SIL (60 µM) either induced differentiation ex vivo, or enhanced differentiation induced by deltanoids, or both. Interestingly, SIL acting alone induced differentiation only in cases in which chromosome aberrations could not be detected. In eleven samples sufficient material was available for a limited analysis of the underlying events. Quantitative RT-PCR showed that differentiation markers were upregulated at the mRNA level by both SIL and deltanoids, suggesting that intracellular signaling pathways upstream of transcription factors (TFs) were activated by these agents. Western analysis for proteins which function as TFs in deltanoid-induced monocytic differentiation, such as members of Jun and C/EBP families, surprisingly demonstrated that SIL upregulated all these TFs in the cases tested. This suggests that although the presence of SIL may not always be sufficient to induce differentiation, it can serve as a differentiation enabling factor for blasts obtained from a large proportion of patients with AML. Thus, SIL/deltanoid combinations warrant further consideration as preventive/therapeutic regimens in human leukaemia. Copyright © 2009 John Wiley & Sons, Ltd.

Burkitt lymphoma versus diffuse large B-cell lymphoma: a practical approach

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an 'aggressive B-cell non-Hodgkin's lymphoma', characterized by a high degree of proliferation of the malignant cells and deregulation of the c-MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B-cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear-cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the two diseases require different management. This review summarizes the current practical approach, including the use of a large panel of antibodies, and cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL and the provisional category of 'B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma', now listed in the updated WHO classification. Copyright © 2009 John Wiley & Sons, Ltd.

Outcomes for lymphoid malignancies in the Nurses' Health Study (NHS) as compared to the Surveillance, Epidemiology and End Results (SEER) Program

Vital statistics for the lymphoid malignancies obtained from the Surveillance, Epidemiology and End Results (SEER) Program have seldom been directly compared to data from alternative national databases. While SEER is recognized as the standard, some lymphoid malignancies - especially the chronic ones - may be underreported. We compared the incidence, all-cause and cause-specific mortality for Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) in SEER to that in the Nurses' Health Study (NHS), a national cohort study of 121 700 female registered nurses, matching for age and race. In over 2.5 million person-years, the incidence of HL was the same as in SEER (SIR = 1.01 [0.75, 1.26]), while the incidence of NHL, CLL and MM were slightly higher. All-cause mortality was lower for the lymphoid malignancies except for MM, which was the same; there were no differences in cause-specific mortality, except for MM (HR = 1.26 [1.07, 1.48]). Our analysis suggests that, at least among white women, SEER is a reliable data source with respect to lymphoid malignancies. Copyright © 2009 John Wiley & Sons, Ltd.

Dynamic change of T315I BCR-ABL kinase domain mutation in Korean chronic myeloid leukaemia patients during treatment with Abl tyrosine kinase inhibitors

We analysed the dynamic change of imatinib-resistant mutations in BCR-ABL kinase domain focusing on T315I mutation during dasatinib or nilotinib therapy. Fifty-five imatinib-resistant chronic myeloid leukaemia patients (32 patients with imatinib-resistant mutations and 23 patients without mutation) in different disease phases were treated with dasatinib (median 17.3 months) or nilotinib (median 6.8 months). Among the 32 patients with baseline mutation, mutations including M244V, G250E, E255K, M351T, H396R, S417Y, E450K and E459K disappeared in 8 patients and new mutations were detected in 9 patients, all of which were T315I. Among the 23 patients without baseline mutation, 4 patients showed newly developed mutations including T315I, T315I + E459K, M244V and F359V. The T315I was the most frequently detected mutation in imatinib therapy (16%, 9 of 55) as well as in dasatinib or nilotinib therapy (24%, 11 of 44). Patients with imatinib resistant baseline mutations had a higher rate of mutation development during dasatinib or nilotinib treatment compared to patients without baseline mutations (28% vs. 17%). Copyright © 2009 John Wiley & Sons, Ltd.

Clofarabine in the treatment of poor risk acute myeloid leukaemia

Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients. Copyright © 2009 John Wiley & Sons, Ltd.

Clinical characteristics of patients with chronic eosinophilic leukaemia (CEL) harbouring FIP1L1-PDGFRA fusion transcript - results of Polish multicentre study

A small subgroup of patients with hypereosinophilic syndrome (HES) demonstrates imatinib-sensitive fusion transcript - the FIP1L1-PDGFRA (F/P+). These cases are currently diagnosed as chronic eosinophilic leukaemia (CEL). In this paper, we screened 77 patients to estimate the frequency of FIP1L1-PDGFRA transcript among patients with unexplained, long-term hypereosinophilia exceeding 1.5 × 109/L and to analyse the clinical and serological features in F/P+ CEL population. The FIP1L1-PDGFRA chimeric protein was detectable in 16 (14 males and 2 females) out of 77 examined HES patients (20%) by RT-PCR. Two patients suffered from cough at diagnosis. Three out of 16 (18%) patients had no organ involvements, in 5-one organ was affected and in the remaining eight cases - at least two. Eosinophilic organ damage/dysfunction identified splenomegaly in the majority of studied patients. We compared clinical and serological features between CEL F/P+ (n = 16) and HES (n = 61) patients. F/P+ cases had significantly increased WBC and absolute eosinophil count (AEC) at diagnosis (p = 0.008 and 0.02), whereas platelet count was decreased in this population (p = 0.03). Serum B12 and tryptase levels were increased (p = 0.002 and 0.004) in CEL F/P+ patients when compared to HES cases whereas serum IL-5 levels were significantly increased in the latter group (p = 0.01). Male gender and splenomegaly occurred more frequent in CEL F/P+ population (p = 0.002 and 0.0007, respectively). Additionally, patients with F/P+ CEL (n = 16) were compared with F/P- CEL (n = 8). The latter group, was significantly older, had lower AEC and higher platelet count. In conclusion, significant clinical symptoms are infrequent present and splenomegaly remains the most common organ involvement in patients with CEL expressing F/P fusion transcript. Our study confirmed the long-term remission on imatinib in this patient population. Copyright © 2009 John Wiley & Sons, Ltd.

Cytogenetic and molecular responses in chronic phase chronic myeloid leukaemia patients receiving low dose of imatinib for intolerance to standard dose

Imatinib mesylate is the gold standard treatment of chronic myeloid leukaemia (CML) and 400 mg/day is considered the standard dose. Although it is generally well tolerated, some patients require temporary drug discontinuation and permanent dose reduction because of haematological or non-haematological toxicities. Whether or not reduced doses are effective as the standard dose in inducing and/or maintaining complete cytogenetic and molecular response is not clear. We report the outcome of 45 CML patients in early (17) and late (28) chronic phase (CP) in whom, within a series of 250 patients treated with imatinib, reduced the dose of the drug after experiencing adverse events. Median time interval between the start of therapy and dose reduction was 58 days, whereas median administered dose was 300 mg/day. At 6 months from reduction, major cytogenetic responses (MCRs) were observed in 67% of patients, with 58% being complete cytogenetic remission (CCR), and complete molecular response (CMR) were obtained in 18% of patients. At 12 months, all patients who had obtained MCR reached CCR: this was significantly higher in low risk patients (87%) versus non-low risk patients (66 and 46%), and in early phase (82%) versus late phase (53.5%). CMR and major molecular response (MMR) were detected in 20 and 22% of patients, respectively. Low dose imatinib appears effective in patients with intolerance to standard dose, even though long-term effects remain to be established. Copyright © 2009 John Wiley & Sons, Ltd.

Geographic variation and environmental conditions as cofactors in Chlamydia psittaci association with ocular adnexal lymphomas: a comparison between Italian and African samples

A particular extra-nodal lymphoma type arises from B cells of the marginal zone (MZ) of mucosa-associated lymphoid tissue (MALT). The aetiology of MZ lymphomas suggests that they are associated with chronic antigenic stimulation by microbial pathogens, among which Helicobacter pylori-associated gastric MALT lymphoma is the best studied. Recently, MALT lymphomas have been described in the context of chronic conjunctivitis, which can be associated with Chlamydia spp. infection. Studies from Italy showed the presence of Chlamydia psittaci in 87% of ocular adnexal lymphomas (OAL), and C. psittaci has been described in a large part of samples from Austria and Korea as well. However, this finding was not always confirmed by other studies, suggesting that the association with C. psittaci may depend on geographic heterogeneity. Interestingly, none of the studies up to now has been carried out in the African population, where a strong association between infectious agents and the occurrence of human neoplasms has been reported. This study was designed to investigate the possible association of Chlamydia psittaci in cases retrieved from Kenya, compared to cases from Italy. Our results showed that there was a marked variation between the two geographical areas in terms of association with C. psittaci, as 17% (5/30) of the samples from Italy were positive for C. psittaci, whereas no association with this pathogen was observed in any of the African samples (0/9), suggesting that other cofactors may determine the OAL occurrence in those areas. OAL cases are often characterized by down-regulation of p16/INK4a expression and promoter hypermethylation of the p16/INK4a gene. Our results showed a partial methylation of p16/INK4a promoter in C. psittaci-negative cases, whereas no hypermethylation of this gene was found in C. psittaci-positive cases, suggesting that mechanisms other than promoter hypermethylation lead to p16/INK4a silencing in C. psittaci-positive cases. We may conclude that the role of epidemiologic, environmental and genetic factors, must be considered in the aetiology of this disease. Copyright © 2009 John Wiley & Sons, Ltd.

CT-guided percutaneous lung biopsies in patients with haematologic malignancies and undiagnosed pulmonary lesions

We searched the electronic patient database at The University of Texas M. D. Anderson Cancer Center for patients who underwent computed tomography (CT)-guided needle biopsy between January 2001 and December 2005. Inclusion criteria were a known history of haematologic malignancy and a newly detected, undiagnosed pulmonary lesion on chest CT that required tissue sampling for diagnosis; 213 met these criteria. We analysed the biopsy results for diagnostic yield, factors affecting diagnostic yield and effect on treatment. Of 213 procedures, 191 (89.7%) yielded sufficient material for pathologic analysis; 130 (60%) yielded specific diagnoses, while 61 (28.6%) yielded nonspecific benign diagnoses. Lesions larger than 1 cm, cavitary lesions and lung masses were more likely to yield a specific diagnosis than were lesions smaller than 1 cm, lung nodules and consolidations. The most common specific diagnoses were malignancy (62.8%) and infection (34.3%). The latter was more common in patients with leukaemia, cavitary lung lesions or consolidations, active underlying malignancy, neutropenia, respiratory signs and symptoms and/or fever, bone marrow transplant recipients, and in patients receiving chemotherapy. Lung lesions discovered upon follow-up imaging in patients who did not have any respiratory signs/symptoms or fever were mostly malignant. Therapeutic changes were more likely after a specific diagnosis than after a nonspecific diagnosis or a nondiagnostic biopsy (88.4% vs. 18.1%; p < 0.0001). CT-guided lung biopsy has a high diagnostic yield in patients with haematologic malignancies that present with unexplained pulmonary lesions and provides a specific diagnosis in a majority of these patients, leading to therapeutic changes. Copyright © 2009 John Wiley & Sons, Ltd.

Severe pulmonary complications after bortezomib treatment in multiple myeloma

No Abstract.

The root of many evils: indolent large granular lymphocyte leukaemia and associated disorders

Large granular lymphocytes (LGL) leukaemia can arise from either natural killer (NK) cells or cytotoxic T lymphocytes (CTL). The T-cell form of LGL leukaemia has significant overlap with other haematological disorders and autoimmune diseases. Here we provide an overview of LGL biology. We also focus discussion on the indolent LGL leukaemia related disorders and their causal relationships. We then discuss the potential relationships and distinctions between indolent LGL leukaemia and non-malignant clonal lymphocyte expansion that occur in otherwise healthy individuals, especially elder people. Copyright © 2009 John Wiley & Sons, Ltd.

Remission induction, consolidation and novel agents in development for adults with acute myeloid leukaemia

Chemotherapy regimens used for remission induction in AML have not changed significantly over the last several decades. However the recognition of the prognostic value of cytogenetics and genomics has been a major advance which is helping clarify the most optimal post-remission consolidation strategy among various risk groups. We are not only beginning to realize the pitfalls of a 'one-fits-all' approach with intensive, cytarabine-based chemotherapy as the mainstay, but we are finally beginning to reap the rewards of decades of basic, translational, and clinical research. Developing individualized, 'targeted' therapy for each AML patient based on unique molecular features of disease remains a daunting goal yet one that we can now begin to envision. Hypothesis-based study designs - from pre-clinical/laboratory experiments to phase-I and subsequent efficacy trials - provide the foundation for advances in the diagnosis, risk stratification, and treatment for patients with AML. Here we critically review the literature for the management of AML, try to give recommendations regarding the appropriate induction and remission strategy, clarify the role of stem cell transplantation and discuss novel agents on the horizon. Copyright © 2009 John Wiley & Sons, Ltd.

18F-FDG uptake and its clinical relevance in primary gastric lymphoma

We studied the clinical relevance of 18F-fluorodeoxyglucose (18F-FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty-two patients with primary gastric lymphoma were analysed: 32 diffuse large B-cell lymphomas (DLBCL) and 10 extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up-staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down-staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax [ge] median value, was significantly associated with an advanced Lugano stage (p < 0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow-up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual 18F-FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual 18F-FDG uptake observed during follow-up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. Copyright © 2009 John Wiley & Sons, Ltd.

Two novel NPM1 mutations in a therapy-responder AML patient

Nucleophosmin 1 (NPM1) is an abundant phosphoprotein mainly located in the nucleolus but also shuttling between the nucleus and cytoplasm. NPM1 has been proposed to be involved in synthesis and processing of ribosomal RNA, regulation of chromatin structure and transport of rRNA and ribosomal proteins. NPM1 gene is considered to be implicated in human cancer as it is a frequent target of genetic alterations, primarily in haematopoietic neoplasms. We describe a case of a therapy-responder acute myeloid leukaemia (AML) patient bearing two novel NPM1 mutations. Cells' transfection studies indicate that the presence of one of these mutations is associated to an abnormal nucleolar structure, suggesting that NPM1 may contribute to the control of nucleolar integrity. Copyright © 2009 John Wiley & Sons, Ltd.

Experimental and clinical characteristics in myelodysplastic syndrome patients with or without HLA-DR15 allele

We studied the effects of the presence of the HLA-DR15 allele on the experimental and clinical features of myelodysplastic syndrome (MDS) by assessing the clinical data of 136 patients with MDS. We observed that the frequency of HLA-DR15 expression in MDS patients (38.7%) was significantly higher than that in the healthy controls (p < 0.01). We noted the following observations with regard to disease progression: None of the 46 HLA-DR15 positive patients with international prognostic scoring system (IPSS) scores [le]1 developed acute myeloid leukaemia (AML) during the follow-up period, while six of the 63 DR15-negative patients with the same IPSS score developed AML within a shorter follow-up period (p = 0.039). Furthermore, the incidence of poor chromosomal abnormalities, the percentage of patients with IPSS scores [ge]1.5 and the presence of [ge]5% blasts in the bone marrow in the DR15-positive patients were lower than the corresponding findings in the DR15-negative patients. In addition, we also recorded the following observations with regard to bone marrow (BM) failure: The bicytopenia/pancytopenia ratio in the DR15-positive patients was higher than that in the DR15-negative patients (92.4 vs. 78.3%; p = 0.029). The peripheral-neutrophil count and the platelet count in the DR15-positive patients were lower than those in the DR15-negative patients (p = 0.028 and p = 0.011, respectively). Moreover, hypocellularity was more easily detectable in the DR15-positive patients (26.4 vs. 16.9%). In addition, the BM CD4+ lymphocyte count and the CD4/CD8 ratio in the DR15-positive patients were higher than the corresponding values in the DR15-negative patients (p < 0.05 for both). However, there were no significant differences between the polarization of T-helper (Th) and T-cytotoxic (Tc) cells and the cytokine levels in these two patient groups. We concluded that the presence of the HLA-DR15 allele is indicative of a genetic susceptibility to MDS and, the presence of the HLA-DR15 allele showed less association with disease progression and greater association with BM failure. Copyright © 2009 John Wiley & Sons, Ltd.

Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy

Many patients with primary myelofibrosis (PMF) become red blood cell (RBC) transfusion dependent (TD), risking iron overload (IOL). Iron chelation therapy (ICT) may decrease the risk of haemosiderosis associated organ dysfunction, though its benefit in PMF is undefined. To assess the effect of TD and ICT on survival in PMF, we retrospectively reviewed 41 patients. Clinical data were collected from the database and by chart review. The median age at PMF diagnosis was 64 (range 43-86) years. Median white blood cell (WBC) count at diagnosis was 7.6 (range 1.2-70.9) × 109/L; haemoglobin 104 (62-145) G/L; platelets 300 (38-2088) × 109/L. Lille, Strasser, Mayo and International Prognostic System (IPS) scores were: low risk, n = 15, 8, 11, 3; intermediate, n = 15, 19, 9, 16; high, n = 5, 11, 5, 7; respectively. Primary PMF treatment was: supportive care, n = 23; hydroxyurea, n = 10; immunomodulatory, n = 4; splenectomy, n = 2. Sixteen patients were RBC transfusion independent (TI) and 25 TD; of these 10 received ICT for a median of 18.3 (0.1-117) months. Pre-ICT ferritin levels were a median of 2318 (range 263-8400) and at follow up 1571 (1005-3211 µg/L (p = 0.01). In an analysis of TD patients, factors significant for overall survival (OS) were: WBC count at diagnosis (p = 0.002); monocyte count (p = 0.0001); Mayo score (p = 0.05); IPS (p = 0.02); number of RBC units (NRBCU) transfused (p = 0.02) and ICT (p = 0.003). In a multivariate analysis, significant factors were: NRBCU (p = 0.001) and ICT (p = 0.0001). Five year OS for TI, TD-ICT and TD-NO ICT were: 100, 89 and 34%, respectively (p = 0.003). The hazard ratio (HR) for receiving >20 RBCU was 7.6 (95% Confidence Intervals [CI] 1.2-49.3) and for ICT was 0.15 (0.03-0.77). In conclusion, 61% of PMF patients developed RBC-TD which portended inferior OS; however patients receiving ICT had comparatively improved OS, suggesting a clinical benefit. Prospective studies of IOL and the impact of ICT in PMF are warranted. Copyright © 2009 John Wiley & Sons, Ltd.

The therapeutic effect of rituximab on CD5-positive and CD5-negative diffuse large B-cell lymphoma

The prognosis of diffuse large B-cell lymphoma (DLBCL) has improved markedly in recent years of rituximab era. The prognosis of de novo CD5-positive DLBCL is reported to be poor, but the effect of rituximab on this type of lymphoma remains unclear. To investigate the effect of rituximab on CD5-positive DLBCL, we collected DLBCL patients and analysed prognostic factors. A total of 157 patients with DLBCL who were immunophenotyped with flow-cytometry (FCM) and treated with chemotherapy were subjected to analysis. Those treated with radiotherapy alone or with supportive therapy only were not included. Patients diagnosed in 2003 or later were treated with rituximab combined chemotherapy. There were 95 males and 62 females. Their age ranged from 20 to 91 years old, and the median was 65 years. Nineteen patients were diagnosed as having de novo CD5-positive DLBCL. Rituximab was given alongside chemotherapy in 85 patients. Of these, 11 were positive for CD5 and 74 were negative. The addition of rituximab improved the overall survival (OS) of DLBCL patients (2-year OS: 82% vs. 70%, p = 0.01). For CD5-negative DLBCL, patients treated with rituximab showed 2-year OS of 84%, which was significantly better than those treated without rituximab (70%, p = 0.008). However, for CD5-positive DLBCL, the prognosis was not statistically different between the patients treated with and without rituximab (59% vs. 50%, p = 0.72). Although rituximab improved the prognosis of DLBCL, such improvement was restricted to the CD5-negative group. Further investigation is required to improve the prognosis of patients with CD5-positive DLBCL. Copyright © 2009 John Wiley & Sons, Ltd.

MPL W515L/K mutations in 343 Chinese adults with JAK2V617F mutation-negative chronic myeloproliferative disorders detected by a newly developed RQ-PCR based on TaqMan MGB probes

Acquired mutations in the juxtamembrane region of MPL (W515L or W515K), the receptor for thrombopoietin, have been reported in patients with primary essential thrombocythemia (ET) or primary myelofibrosis (PMF). The mutations were detected by the newly developed real-time quantitative PCR (RQ-PCR) with TaqMan MGB probes and followed by the sequencing analysis. DNA samples were from 343 Chinese adults with JAK2V617F mutation-negative chronic myeloproliferative disorders (cMPDs). Reference curves were obtained using cloned fragments of MPL containing either the wild-type or MPL W515L or MPL W515K mutated sequence; the predicted sensitivity level was at least 0.5%(0.1-0.5%) for MPL W515L and 0.5%(0.2-0.5%) for MPL W515K mutant allele in a wild-type background. The detection rates of MPL W515 mutations were 3.5% in 199 ET patients (7/199), 12.5% in 24 PMF patients (3/24) and 5.6% in 36 cMPD-unclassed patients (2/36), respectively. No MPL W515 mutations were detected in 32 polycythemia vera (PV) patients, 40 chronic myeloid leukaemia (CML) patients, 12 hypereosinophilic syndrome (HES) patients and 29 normal volunteers. The mean calculated burden of MPL mutant alleles using RQ-PCR for MPL W515L/K was 24.88 ± 14.80% (range, 1.10-56.32%). MPL W515L/K patients presented lower haemoglobin levels, compared with the patients with JAK2V617F mutation-positive cMPDs (p < 0.01). The results demonstrated that RQ-PCR was a reliable and sensitive method for large-scale screening of the MPL W515L/K mutation in patients suspected to have a cMPD. It can also provide a quantitative estimate of mutant allele burden that might be useful for both patient prognosis and monitoring response to therapy. Copyright © 2009 John Wiley & Sons, Ltd.

Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma

Abstract The data about the fatty acid (FA) status of non-Hodgkin lymphoma (NHL) patients are poor. Therefore, the aim of this study was to investigate the FA profile of serum phospholipids in NHL patients related to the aggressiveness and clinical stage of NHL. We analyzed the FA profile of serum phospholipids in 47 newly diagnosed, untreated NHL patients and in 29 healthy subjects. Significantly higher (p < 0.001) levels of palmitic (16:0), oleic (18:1 n-9) and arachidonic acids (20:4 n-6), saturated and monounsaturated FA were found in NHL patients, while linoleic acid (18:2 n-6) and the levels of total polyunsaturated FA (PUFA), n-3 PUFA, eicosapentaenoic (20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) were significantly reduced (p < 0.01). The level of oleic acid in patients with indolent NHL was significantly lower (p < 0.05) than in more aggressive types of disease. Contents of palmitoleic acid, docosatetraenoic (22:4 n-6), and PUFA was lower in very aggressive NHL. According to clinical stage (CS), patients with CS I had significantly higher SFA and lower n-6 FA than other three groups, and group with CS IV showed significantly decreased DHA and n-3 PUFA. Our results showed an abnormal FA profile in serum phospholipids in NHL patients. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-010-0904-6Authors Zorica Cvetković, Clinical Hospital Center Zemun Department of Hematology Vukova 9 11080 Belgrade SerbiaVesna Vučić, University of Belgrade Institute for Medical Research, Department for Nutrition and Metabolism Tadeusa Koscuska 1 11129 Belgrade SerbiaBora Cvetković, Clinical Hospital Center Zemun Department of Urology Vukova 9 11080 Belgrade SerbiaMilan Petrović, Clinical Center of Serbia Institute for Hematology Pasterova 2 11000 Belgrade SerbiaDanijela Ristić-Medić, University of Belgrade Institute for Medical Research, Department for Nutrition and Metabolism Tadeusa Koscuska 1 11129 Belgrade SerbiaJasna Tepšić, University of Belgrade Institute for Medical Research, Department for Nutrition and Metabolism Tadeusa Koscuska 1 11129 Belgrade SerbiaMaria Glibetić, University of Belgrade Institute for Medical Research, Department for Nutrition and Metabolism Tadeusa Koscuska 1 11129 Belgrade Serbia Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Ciprofloxacin-induced acute haemolytic anaemia in a patient with glucose-6-phosphate dehydrogenase Mediterranean deficiency: a case report

Ciprofloxacin-induced acute haemolytic anaemia in a patient with glucose-6-phosphate dehydrogenase Mediterranean deficiency: a case report Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-010-0903-7Authors Stefano Sansone, Central Hospital of Bolzano Division of Internal Medicine Lorenz-Böhler Street 5 39100 Bolzano ItalyJohanna Rottensteiner, Central Hospital of Bolzano Division of Internal Medicine Lorenz-Böhler Street 5 39100 Bolzano ItalyJudith Stocker, Central Hospital of Bolzano Division of Oncology Lorenz-Böhler Street 5 39100 Bolzano ItalyCarlo Rosanelli, Central Hospital of Bolzano Division of Hematology and Bone Marrow Transplantation Lorenz-Böhler Street 5 39100 Bolzano ItalyChristian Josef Wiedermann, Central Hospital of Bolzano Division of Internal Medicine Lorenz-Böhler Street 5 39100 Bolzano Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Hyperlipidemic myeloma

Hyperlipidemic myeloma Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-010-0905-5Authors Alessandro Gozzetti, University of Siena Division of Hematology and Transplants, Policlinico “Santa Maria alle Scotte” Viale Bracci 16 53100 Siena ItalyMarzia Defina, University of Siena Division of Hematology and Transplants, Policlinico “Santa Maria alle Scotte” Viale Bracci 16 53100 Siena ItalyMonica Bocchia, University of Siena Division of Hematology and Transplants, Policlinico “Santa Maria alle Scotte” Viale Bracci 16 53100 Siena ItalyFrancesco Lauria, University of Siena Division of Hematology and Transplants, Policlinico “Santa Maria alle Scotte” Viale Bracci 16 53100 Siena Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Mechanisms of resistance against PKC412 in resistant FLT3-ITD positive human acute myeloid leukemia cells

Abstract Treatment of acute myeloid leukemia (AML) remains challenging with many patients harboring unfavorable prognostic parameters such as FLT3 internal tandem duplication (FLT3-ITD) mutations leading to a constitutively activated FLT3-receptor tyrosine kinase (RTK). Activation of proteins by phosphorylation of tyrosine residues is a common mechanism in leukemia development. Therefore, specific tyrosine kinase inhibitors (TKI) have been developed for AML therapy and are currently under investigation. The staurosporine derivate PKC412 (Midostaurin) was found to be an effective inhibitor of the FLT3-RTK and is currently undergoing clinical trials for FLT3-mutated AML patients. Since resistance towards TKIs has been observed in vitro and in clinical trials, we have generated a PKC412-resistant clone (MV4-11r) of the human myelomonoblastic cell line MV4-11, which carries a homozygous FLT3-ITD mutation. MV4-11r displayed higher vitality after addition of PKC412 compared with MV4-11 with a pronounced reduction of apoptotic cells. Cytogenetic characterization revealed the acquisition of additional aberrations in the resistant cell line such as clonal alterations at chromosome 13q with additional FLT3 signals. Microarray analysis revealed significant expression changes in several genes prior to and after incubation with PKC412. The expression status of candidate genes being regulated by FLT-ITD like JAG1, p53, MCL-1, C-KIT, and FLT3/-L was confirmed by real-time PCR. In summary, resistance against PKC412 appears to be mediated by up-regulation of anti-apoptotic genes and down-regulation of proapoptotic signals as well as genes that are involved in normal and malignant hematopoiesis. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0889-1Authors Friedrich Stölzel, Universitätsklinikum Carl Gustav Carus Dresden der TU Dresden Medizinische Klinik und Poliklinik I Fetscherstr. 74 01307 Dresden GermanyChristine Steudel, Universitätsklinikum Carl Gustav Carus Dresden der TU Dresden Medizinische Klinik und Poliklinik I Fetscherstr. 74 01307 Dresden GermanyUta Oelschlägel, Universitätsklinikum Carl Gustav Carus Dresden der TU Dresden Medizinische Klinik und Poliklinik I Fetscherstr. 74 01307 Dresden GermanyBrigitte Mohr, Universitätsklinikum Carl Gustav Carus Dresden der TU Dresden Medizinische Klinik und Poliklinik I Fetscherstr. 74 01307 Dresden GermanySina Koch, Universitätsklinikum Carl Gustav Carus Dresden der TU Dresden Medizinische Klinik und Poliklinik I Fetscherstr. 74 01307 Dresden GermanyGerhard Ehninger, Universitätsklinikum Carl Gustav Carus Dresden der TU Dresden Medizinische Klinik und Poliklinik I Fetscherstr. 74 01307 Dresden GermanyChristian Thiede, Universitätsklinikum Carl Gustav Carus Dresden der TU Dresden Medizinische Klinik und Poliklinik I Fetscherstr. 74 01307 Dresden Germany Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Serological response to influenza vaccine after hematopoetic stem cell transplantation

Abstract Vaccination is the best strategy to prevent influenza infection that is a potential cause of morbidity and mortality in immunosuppressed patients. Here, we evaluated the factors that may affect serological response to influenza vaccine in patients who have undergone hematopoetic stem cell transplantation (HSCT). Sixty-one HSCT recipients were included in the study during the 2007–2008 influenza season. Serum samples prior to vaccination and 6–10 weeks after vaccination were collected. Samples were assayed for antibodies to influenza virus A/H1N1, A/H3N2, and B strains by hemagglutination-inhibition assay. The patients were followed in terms of clinical symptoms up to the next influenza season and for adverse effects within a month after vaccination. Overall, pre-vaccine seroprotection rate against all vaccine antigens (A/H1N1, A/H3N2, and B antigens) was 45.1%, post-vaccine seroprotection rate 91% and seroconversion rate was 28.3%. Seroconversion rates were found to be low against B in patients who were vaccinated in the late influenza season (p = 0.018; respectively). Five patients (10.9%) had no immune response against H1N1. Adverse events were reported in 19.6% (n = 9/46) of the patients. In conclusion, the patients should be vaccinated as early as possible in the influenza season, before they are exposed to the virus. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0897-1Authors S. Songül Yalçın, Hacettepe University Unit of Social Pediatrics, Department of Pediatrics, Faculty of Medicine 06100 Ankara TurkeyMeda Kondolot, Hacettepe University Unit of Social Pediatrics, Department of Pediatrics, Faculty of Medicine 06100 Ankara TurkeyNurhan Albayrak, Virology Unit of Refik Saydam Hıfzıssıha Center Ankara TurkeyA. Başak Altaş, Virology Unit of Refik Saydam Hıfzıssıha Center Ankara TurkeyYasemin Karacan, Hacettepe University Unit of Hematopoetic Stem Cell Transplantation, Department of Internal Medicine, Faculty of Medicine Ankara TurkeyBarış Kuşkonmaz, Hacettepe University Unit of Hematopoetic Stem Cell Transplantation, Department of Pediatrics, Faculty of Medicine Ankara TurkeySalih Aksu, Hacettepe University Unit of Hematopoetic Stem Cell Transplantation, Department of Internal Medicine, Faculty of Medicine Ankara TurkeyMualla Çetin, Hacettepe University Unit of Hematopoetic Stem Cell Transplantation, Department of Pediatrics, Faculty of Medicine Ankara TurkeyHakan Göker, Hacettepe University Unit of Hematopoetic Stem Cell Transplantation, Department of Internal Medicine, Faculty of Medicine Ankara TurkeyKadriye Yurdakök, Hacettepe University Unit of Social Pediatrics, Department of Pediatrics, Faculty of Medicine 06100 Ankara TurkeyDuygu Uçkan, Hacettepe University Unit of Hematopoetic Stem Cell Transplantation, Department of Pediatrics, Faculty of Medicine Ankara Turkey Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

Abstract Hematopoietic recovery after high-dose chemotherapy (HDC) in the treatment of hematological diseases may be slow and/or incomplete. This is generally attributed to progressive hematopoietic stem cell failure, although defective hematopoiesis may be in part due to poor stromal function. Chemotherapy is known to damage mature bone marrow stromal cells in vitro, but the extent to which marrow mesenchymal stem cells (MSCs) are damaged by HDC in vivo is largely unknown. To address this question, the phenotype and functional properties of marrow MSCs derived from untreated and chemotherapeutically treated patients with hematological malignancy were compared. This study demonstrates a significant reduction in MSC expansion and MSC CD44 expression by MSCs derived from patients receiving HDC regimens, thus implicating potential disadvantages in the use of autologous MSCs in chemotherapeutically pretreated patients for future therapeutic strategies. The clinical importance of these HDC-induced defects we have observed could be determined through prospective randomized trials of the effects of MSC cotransplantation on hematopoietic recovery in the setting of HDC with and without hematopoietic stem cell rescue. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0896-2Authors Kevin Kemp, University of the West of England Center for Research in Biomedicine, Faculty of Applied Sciences Bristol UKRuth Morse, University of the West of England Center for Research in Biomedicine, Faculty of Applied Sciences Bristol UKSarah Wexler, Royal United Hospital Department of Hematology Bath UKChristine Cox, Royal United Hospital Department of Hematology Bath UKElizabeth Mallam, University of Bristol Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, Clinical Sciences North Bristol Bristol UKJill Hows, University of the West of England Center for Research in Biomedicine, Faculty of Applied Sciences Bristol UKCraig Donaldson, University of the West of England Center for Research in Biomedicine, Faculty of Applied Sciences Bristol UK Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Areas with high soil percolation by herbicides have higher incidence of low-grade non-Hodgkin lymphomas

Areas with high soil percolation by herbicides have higher incidence of low-grade non-Hodgkin lymphomas Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0898-0Authors Rita Fazzi, University of Pisa Division of Hematology, Department of Oncology, Transplants and Advances in Medicine Pisa ItalyChiara Manetti, Division of Oncology, Azienda Ospedaliera Lucca Lucca ItalyDaniele Focosi, University of Pisa Division of Hematology, Department of Oncology, Transplants and Advances in Medicine Pisa ItalyLucia Miligi, Environmental and Occupational Epidemiology Institute for Study and Cancer Prevention, ISPO Florence ItalyAlessandra Benvenuti, Environmental and Occupational Epidemiology Institute for Study and Cancer Prevention, ISPO Florence ItalyEnrico Bonari, Scuola Superiore di Studi Universitari e Perfezionamento Sant’Anna Pisa ItalyRoberto Barale, University of Pisa Division of Genetics Pisa ItalyMario Petrini, University of Pisa Division of Hematology, Department of Oncology, Transplants and Advances in Medicine Pisa Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain

Abstract Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status, in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2% in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote, H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish Mediterranean population. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-010-0901-9Authors Núria Aranda, Universitat Rovira i Virgili IISPV Tarragona SpainFernando E. Viteri, University of California, Children’s Hospital Oakland Research Institute (CHORI) Nutritional Sciences and Toxicology, Morgan Hall Oakland USACarme Montserrat, Universitat Rovira i Virgili IISPV Tarragona SpainVictoria Arija, Universitat Rovira i Virgili IISPV Tarragona Spain Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Two case reports of non-secretary-Ig types of lymphoplasmacytic lymphoma (LPL)

Two case reports of non-secretary-Ig types of lymphoplasmacytic lymphoma (LPL) Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-010-0902-8Authors Kichinosuke Kobayashi, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 JapanTaiji Yokote, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 JapanYuji Hirata, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 JapanShoko Nakayama, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 JapanNobuya Hiraoka, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 JapanAyami Takayama, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 JapanKazuki Iwaki, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 JapanToshikazu Akioka, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 JapanTakayuki Takubo, Osaka Medical College Division of Comprehensive Diagnostic and Therapeutics, Department of Clinical and Laboratory Medicine Takatsuki JapanMotomu Tsuji, Osaka Medical College Division of Surgical Pathology Takatsuki JapanToshiaki Hanafusa, Osaka Medical College Department of Internal Medicine (I) 2-7 Daigakumachi Takatsuki Osaka 569-0801 Japan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Increased osteoclastic activity as shown by increased sRANK-L/OPG ratio in boys with hemophilia

Increased osteoclastic activity as shown by increased sRANK-L/OPG ratio in boys with hemophilia Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0894-4Authors Athanasios Christoforidis, Aristotle University of Thessaloniki First Paediatric Department 59, Konstantinoupoleos Str 54642 Thessaloniki GreeceMarina Economou, Aristotle University of Thessaloniki First Paediatric Department 59, Konstantinoupoleos Str 54642 Thessaloniki GreeceEvangelia Farmaki, Aristotle University of Thessaloniki First Paediatric Department 59, Konstantinoupoleos Str 54642 Thessaloniki GreeceVasiliki Tzimouli, Aristotle University of Thessaloniki First Paediatric Department 59, Konstantinoupoleos Str 54642 Thessaloniki GreeceNikos Gombakis, Aristotle University of Thessaloniki First Paediatric Department 59, Konstantinoupoleos Str 54642 Thessaloniki GreeceMiranda Athanassiou-Metaxa, Aristotle University of Thessaloniki First Paediatric Department 59, Konstantinoupoleos Str 54642 Thessaloniki Greece Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

T-cell large granular lymphocyte leukemia: an Asian perspective

Abstract To characterize T-cell large granular leukemia in Asia, 22 Chinese patients from a single institute were reported, together with an analysis of 88 Asian and 272 Western patients identified from the literature. In our cohort, anemia due to pure red cell aplasia (PRCA) occurred in 15/22 (68%) of cases, being the most common indication for treatment. Neutropenia was only found in 8/22 (36%) cases, and recurrent infections, the most important clinical problem in Western patients, were not observed. None of our cases presented with rheumatoid arthritis. These clinical features were consistently observed when compared with the 88 other Asian patients. Combined data from our cohort and other Asian cases showed that Asian patients, compared with Western patients, had more frequent anemia (66/110, 60% versus 113/240, 47%; p = 0.044), attributable to a much higher incidence of PRCA (52/110, 47% versus 6/143, 4%; p < 0.001). However, Western patients presented more frequently than Asian patients with neutropenia (146/235, 62% versus 33/110, 30%; p < 0.001) and splenomegaly (99/246, 40% versus 16/110, 15%; p < 0.001). Notably, Western patients were about eight to ten times more likely than Asian patients to have rheumatoid arthritis (73/272, 27% versus 4/106, 4%; p < 0.001) and recurrent infections (81/272, 30% versus 3/107, 3%; p < 0.001). These clinicopathologic differences have important implications on disease pathogenesis and treatment. Content Type Journal ArticleCategory Review ArticleDOI 10.1007/s00277-009-0895-3Authors Yok-Lam Kwong, University of Hong Kong Department of Medicine Hong Kong Special Administrative Region People’s Republic of ChinaWing-Yan Au, University of Hong Kong Department of Medicine Hong Kong Special Administrative Region People’s Republic of ChinaAnskar Y. H. Leung, University of Hong Kong Department of Medicine Hong Kong Special Administrative Region People’s Republic of ChinaEric W. C. Tse, University of Hong Kong Department of Medicine Hong Kong Special Administrative Region People’s Republic of China Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Poor potential of proliferation and differentiation in bone marrow mesenchymal stem cells derived from children with severe aplastic anemia

Abstract The pathogenesis of severe aplastic anemia (SAA) has not been completely understood, and insufficiency of the hematopoietic microenvironment can be an important factor. Here, we compared the basic properties of mesenchymal stem cells (MSCs), a major component of bone marrow microenvironment, from five SAA children with those of MSCs from five controls. Although MSCs from SAA children and controls were similar in morphology and immunophenotypic profile, SAA MSCs had slower expansion rate and smaller cumulative population doubling (1.83 ± 1.21 vs 3.36 ± 0.87; p = 0.046), indicating lower proliferative capacity. After osteogenic induction, SAA MSCs showed lower alkaline phosphatase activity (optical density, 1.46 ± 0.04 vs 2.27 ± 0.32; p = 0.013), less intense von Kossa staining, and lower gene expression of core binding factor α1 (0.0015 ± 0.0005 vs 0.0056 ± 0.0017; p = 0.013). Following adipogenic induction, SAA MSCs showed less intense Oil red O staining (optical density, 0.86 ± 0.22 vs 1.73 ± 0.42; p = 0.013) and lower lipoprotein lipase expression (0.0105 ± 0.0074 vs 0.0527 ± 0.0254; p = 0.013). These findings provided evidence that defects in bone marrow MSCs of SAA children do exist. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0892-6Authors Yu-Hua Chao, Tungs’ Taichung MetroHarbor Hospital Department of Pediatrics Taichung TaiwanChing-Tien Peng, China Medical University Hospital Department of Pediatrics Taichung TaiwanHorng-Jyh Harn, China Medical University Hospital Center for Neuropsychiatry Taichung TaiwanChin-Kan Chan, Chang Gung University Graduate Institute of Clinical Medical Science Taoyuan TaiwanKang-Hsi Wu, China Medical University Hospital Department of Pediatrics Taichung Taiwan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Pancytopenia and severe sepsis in an adult case of congenital X-linked agammaglobulinemia (XLA)

Pancytopenia and severe sepsis in an adult case of congenital X-linked agammaglobulinemia (XLA) Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0891-7Authors Andrea Tendas, Sant’Eugenio Hospital Hematology Unit Rome ItalyPasquale Niscola, Sant’Eugenio Hospital Hematology Unit Rome ItalyTeresa Dentamaro, Sant’Eugenio Hospital Hematology Unit Rome ItalyLuca Cupelli, Sant’Eugenio Hospital Hematology Unit Rome ItalyGigliola Di Matteo, Tor Vergata University Department of Public Health Rome ItalyAndrea Finocchi, Tor Vergata University Department of Public Health Rome ItalyAgostina Siniscalchi, Sant’Eugenio Hospital Hematology Unit Rome ItalyStefano Fratoni, Sant’Eugenio Hospital Pathology Department Rome ItalyTeresa Scimò, Sant’Eugenio Hospital Hematology Unit Rome ItalyLaura Scaramucci, Sant’Eugenio Hospital Hematology Unit Rome ItalyMarco Giovannini, Sant’Eugenio Hospital Hematology Unit Rome ItalyMicaela Ales, Sant’Eugenio Hospital Hematology Unit Rome ItalyAlessio Pio Perrotti, Sant’Eugenio Hospital Hematology Unit Rome ItalyPaolo de Fabritiis, Sant’Eugenio Hospital Hematology Unit Rome Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Protein C (PROC) gene mutations in two Indian families with purpura fulminans

Protein C (PROC) gene mutations in two Indian families with purpura fulminans Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0893-5Authors Navin Pai, National Institute of Immunohaematology (ICMR) Department of Haemostasis and Thrombosis 13th Floor, KEM Hospital, Parel Mumbai 400 012 IndiaShrimati Shetty, National Institute of Immunohaematology (ICMR) Department of Haemostasis and Thrombosis 13th Floor, KEM Hospital, Parel Mumbai 400 012 IndiaKanjaksha Ghosh, National Institute of Immunohaematology (ICMR) Department of Haemostasis and Thrombosis 13th Floor, KEM Hospital, Parel Mumbai 400 012 India Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Pneumocystis jiroveci pneumonia detected by FDG-PET

Pneumocystis jiroveci pneumonia detected by FDG-PET Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0888-2Authors Tomonori Nakazato, Yokohama Municipal Citizen’s Hospital Department of Hematology 56 Okazawa-cho, Hodogaya-ku Yokohama 240-8555 JapanAi Mihara, Yokohama Municipal Citizen’s Hospital Department of Hematology 56 Okazawa-cho, Hodogaya-ku Yokohama 240-8555 JapanYukinari Sanada, Yokohama Municipal Citizen’s Hospital Department of Hematology 56 Okazawa-cho, Hodogaya-ku Yokohama 240-8555 JapanKazuhito Suzuki, Yokohama Municipal Citizen’s Hospital Department of Hematology 56 Okazawa-cho, Hodogaya-ku Yokohama 240-8555 JapanYoshinobu Aisa, Yokohama Municipal Citizen’s Hospital Department of Hematology 56 Okazawa-cho, Hodogaya-ku Yokohama 240-8555 JapanMichio Iwabuchi, Yokohama Municipal Citizen’s Hospital Department of Hematology 56 Okazawa-cho, Hodogaya-ku Yokohama 240-8555 JapanTsunayuki Kakimoto, Yokohama Municipal Citizen’s Hospital Department of Hematology 56 Okazawa-cho, Hodogaya-ku Yokohama 240-8555 Japan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Expression of pSTAT5 predicts FLT3 internal tandem duplications in acute myeloid leukemia

Abstract Mutations of the Fms-like tyrosine kinase 3 (FLT3) can be detected in a significant number of acute myeloid leukemias (AML). Seventy-five cases of acute myeloid leukemia were evaluated for FLT3-internal tandem duplications (ITD) by polymerase chain reaction. Paraffin-embedded formalin-fixed trephine biopsies of these cases were evaluated for expression of phosphorylated signal transducer and activator of transcription 1 (pSTAT1), pSTAT3, and pSTAT5. Specific expression of pSTAT5 was proven in leukemic blasts in situ by double staining with a blast-specific marker. Expression of pSTAT5 in ≥1% of blasts was highly predictive of FLT3-ITD. Neither expression of pSTAT1 nor pSTAT3 were associated with FLT3 mutations. Altogether we conclude that pSTAT5 expression can precisely be assessed by immunohistochemistry in routinely processed bone marrow trephines, STAT5 is highly likely the preferred second messenger of FLT3-mediated signaling in AML, and expression of pSTAT5 is predictive of FLT3-ITD. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0890-8Authors Ellen Christina Obermann, University of Basel Institute of Pathology Schönbeinstrasse 40 4031 Basel SwitzerlandCaroline Arber, University of Basel Hematology Unit Basel SwitzerlandMartine Jotterand, Centre Hospitalier Universitaire Vaudois Unité cytogénétique du cancer Lausanne SwitzerlandAndre Tichelli, University of Basel Hematology Unit Basel SwitzerlandPetra Hirschmann, University of Basel Institute of Pathology Schönbeinstrasse 40 4031 Basel SwitzerlandAlexandar Tzankov, University of Basel Institute of Pathology Schönbeinstrasse 40 4031 Basel Switzerland Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Acquired haemophilia caused by non-haemophilic factor VIII gene variants

Abstract The aetiology of anti-factor VIII (FVIII) autoantibody formation in acquired haemophilia remains unknown. We hypothesised that encounter of antigenically different, allogeneic FVIII may challenge inhibitor formation after presentation on MHC class II. Eighteen consecutive cases with acquired haemophilia were enrolled (nine females, nine males). A control group comprised 50 male and 50 female healthy blood donors. The coding region of the FVIII gene and the HLA-DRB1 genotype were studied. The presentation of foreign FVIII variants on the patient’s MHC class II alleles was predicted using SYFPEITHI algorithm. A rare FVIII variant (E2004K) was found in one patient with acquired haemophilia after massive transfusion; the 2004 K allele was predicted to be presented on the patient’s HLA-DRB1*0101. Moreover, distribution of a polymorphism (D1241E) was significantly skewed comparing patients and controls. Three of three patients with transfusion-associated disease carried 1241D in homozygous or hemizygous form and were predicted to present 1241E (foreign), but not 1241D (self), on their HLA-DRB1*0301. Therefore, encounter of 1241E may result in the presentation of a new T cell epitope in these patients. The same conditions were not found in any patient with acquired haemophilia of other causes. The expected frequency in the general Caucasoid population undergoing transfusion is 3% to 4%. In conclusion, encounter of variant allogeneic FVIII presented on a suitable MHC background could be a risk factor for inhibitor formation. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0887-3Authors Andreas Tiede, Hannover Medical School Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation Feodor Lynen Str. 5 30625 Hannover GermanyRoswith Eisert, Hannover Medical School Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation Feodor Lynen Str. 5 30625 Hannover GermanyAndreas Czwalinna, Hannover Medical School Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation Feodor Lynen Str. 5 30625 Hannover GermanyWolfgang Miesbach, University Hospital Frankfurt Department of Internal Medicine Frankfurt GermanyInge Scharrer, University Hospital Frankfurt Department of Internal Medicine Frankfurt GermanyArnold Ganser, Hannover Medical School Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation Feodor Lynen Str. 5 30625 Hannover Germany Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Shedding of the endothelial receptor tyrosine kinase Tie2 correlates with leukemic blast burden and outcome after allogeneic hematopoietic stem cell transplantation for AML

Abstract Angiogenesis plays an important role in the growth and viability of hematologic malignancies. Emerging data suggest a crucial involvement of the endothelial-specific Tie2 receptor and its antagonistic ligand Angiopoietin-2 (Ang-2) in this process. The purpose of this study was to elucidate whether the soluble domain of the Tie2 receptor (sTie2) predicts outcome in patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Serum levels of sTie2 and Ang-2 were measured by ELISA in 181 AML patients before conditioning for HSCT. The median follow-up time was 22 months after HSCT. Pre-HSCT sTie2 levels were significantly higher in patients (median 2.2 (range 1.8–3.0) ng/mL) compared to healthy controls (1.3 (0.9–1.6); p < 0.0001). Elevated sTie2 levels were independently associated with active AML but did not relate to cytogenetics/mutational status before transplantation. Logistic regression analysis identified elevated sTie2 (odds ratio (OR) 3.07 (95% confidence interval (CI; 1.56–6.04), p = 0.001) as a strong predictor for disease relapse and poor overall survival after HSCT. In a multimarker approach the highest risk for relapse was observed in patients with both elevated sTie2 and elevated Ang-2 (OR 4.07, (95% CI 1.79–9.25) p < 0.0001), as well as patients with both elevated Ang-2 and elevated bone marrow blast count (OR 4.16, (95% CI 1.88–7.36) p < 0.0001). Elevated serum sTie2 levels were related to active leukemia, correlated with the percentage of leukemic blasts in the bone marrow, and independently predicted relapse in AML patients after allogeneic HSCT. Furthermore, our data indicate that Tie2 shedding and Ang-2 release seem to reflect overlapping, but nevertheless distinctive features in leukemia-associated neoangiogenesis. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0869-5Authors Christian Koenecke, Hannover Medical School Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation Carl-Neuberg-Str. 1 30625 Hannover GermanyPhilipp Kümpers, Hannover Medical School Department of Nephrology Hannover GermanyAlexander Lukasz, Hannover Medical School Department of Nephrology Hannover GermanyElke Dammann, Hannover Medical School Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation Carl-Neuberg-Str. 1 30625 Hannover GermanyWillem Verhagen, Hannover Medical School Institute of Virology Hannover GermanyGudrun Göhring, Hannover Medical School Institute of Cellular and Molecular Pathology Hannover GermanyStefanie Buchholz, Hannover Medical School Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation Carl-Neuberg-Str. 1 30625 Hannover GermanyJürgen Krauter, Hannover Medical School Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation Carl-Neuberg-Str. 1 30625 Hannover GermanyMatthias Eder, Hannover Medical School Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation Carl-Neuberg-Str. 1 30625 Hannover GermanyBrigitte Schlegelberger, Hannover Medical School Institute of Cellular and Molecular Pathology Hannover GermanyArnold Ganser, Hannover Medical School Department of Hematology, Hemostasis, Oncology and Stem-Cell Transplantation Carl-Neuberg-Str. 1 30625 Hannover Germany Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y

Abstract Until now, the PFA-100® system has been considered unsuitable for monitoring clopidogrel efficacy. The authors evaluated platelet function in peripheral arterial occlusive disease (PAOD) patients using a new PFA-100® test cartridge (product name: INNOVANCE® PFA P2Y*) specifically designed for this purpose. Twenty-two stable PAOD patients on antithrombotic therapy with clopidogrel alone (n = 22) and 18 patients undergoing a peripheral catheter intervention, preliminarily treated with 100 mg/day of aspirin followed by co-administration of clopidogrel (loading dose 300 mg, maintenance dose 75 mg/day), were enrolled in this study. Defining non-responsiveness to clopidogrel as an aggregation response within the reference range (90% central interval), four (18.2%) non-responders using light transmittance aggregometry (LTA) induced by 5 µM adenosine diphosphate (ADP) and six (27.3%) non-responders using LTA induced by 2 µM ADP (LateAggr >72.1% and >42.9%, respectively) were identified. INNOVANCE® PFA P2Y* determined six (27.3%) non-responders (CT < 87 s). Agreement between the two aggregometry assays and INNOVANCE® PFA P2Y* on the definition of clopidogrel response and non-response exceeded 70%. Only three patients were uniformly identified as clopidogrel non-responders by all three assays. When clopidogrel was co-administered with aspirin, two (11.1%) non-responders to clopidogrel were detected with INNOVANCE® PFA P2Y*, whereas ADP-induced LTA found all patients to be responsive. INNOVANCE® PFA P2Y* appears to be suitable for monitoring the effect of clopidogrel on platelet function. Its sensitivity in detecting responsiveness or non-responsiveness to clopidogrel is comparable to ADP-induced LTA. Additional prospective studies are needed to clarify the clinical relevance of the test results and classification obtained with INNOVANCE® PFA P2Y*. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0881-9Authors Birgit Linnemann, J.W. Goethe University Hospital Frankfurt/Main Division of Vascular Medicine, Department of Internal Medicine Theodor-Stern-Kai 7 60590 Frankfurt GermanyJan Schwonberg, J.W. Goethe University Hospital Frankfurt/Main Division of Vascular Medicine, Department of Internal Medicine Theodor-Stern-Kai 7 60590 Frankfurt GermanyAndreas R. Rechner, Siemens Healthcare Diagnostics Products GmbH Assay Development Hemostasis Marburg GermanyHelen Mani, J.W. Goethe University Hospital Frankfurt/Main Division of Vascular Medicine, Department of Internal Medicine Theodor-Stern-Kai 7 60590 Frankfurt GermanyEdelgard Lindhoff-Last, J.W. Goethe University Hospital Frankfurt/Main Division of Vascular Medicine, Department of Internal Medicine Theodor-Stern-Kai 7 60590 Frankfurt Germany Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study

Abstract Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients achieve remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard- versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP. Sixty patients with idiopathic TTP were randomized to receive methylprednisolone 1 mg/kg/die intravenous or 10 mg/kg/die for 3 days, thereafter, 2.5 mg/kg/die in addition to PE. Both dosages of steroids were well tolerated. At the end of induction therapy (day 23), the percentage of patients failing to achieve complete remission was significantly higher in the standard dose (16 of 30) than in the high-dose group (seven of 30). Also, the number of cases without a good response at day 9 and the number of deaths were higher in the standard-dose arm, but the differences did not reach the statistical significance. Results of present study indicate that the association of PE with high-dose instead of standard-dose steroids reduces the percentage of TTP patients that fail to achieve complete remission. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0877-5Authors Carlo L. Balduini, University of Pavia Internal Medicine, IRCCS Policlinico San Matteo Foundation Pavia ItalyLuigi Gugliotta, Santa Maria Nuova Hospital Haematology Reggio Emilia ItalyMario Luppi, University of Modena and Reggio Emilia Haematology, Department of Oncology, Haematology and Respiratory Diseases Modena ItalyLuca Laurenti, A. Gemelli Hospital Haematology, Catholic University Rome ItalyCatherine Klersy, IRCCS Policlinico San Matteo Foundation Biometry and Clinical Epidemiology Pavia ItalyCarla Pieresca, University of Pavia Internal Medicine, IRCCS Policlinico San Matteo Foundation Pavia ItalyGerlando Quintini, Paolo Giaccone Hospital Haematology-BMT Palermo ItalyFrancesco Iuliano, Giannettasio Hospital Haematology Rossano Calabro ItalyRossana Re, Civitanova Marche Hospital Unit of Medicine Civitanova Marche ItalyPierangelo Spedini, Cremona Hospital Haematology and BMT Cremona ItalyNicola Vianelli, L. and A. Seràgnoli Hospital, University of Bologna Hematology and Oncology Bologna ItalyAlfonso Zaccaria, Ravenna Hospital Oncology Ravenna ItalyEnrico Maria Pogliani, University of Milano Bicocca Haematology-BMT, San Gerardo Hospital Monza ItalyRoberto Musso, Ferrarotto University Hospital Haematology Catania ItalyEnrico Bobbio Pallavicini, Crema Hospital Haematology and Oncology Crema ItalyGiovanni Quarta, A. Perrino Hospital Haematology Brindisi ItalyPiero Galieni, Mazzoni Hospital Haematology Ascoli Piceno ItalyAlberto Fragasso, Madonna delle Grazie Hospital Internal Medicine Matera ItalyGianluca Casella, University of Pavia Internal Medicine, IRCCS Policlinico San Matteo Foundation Pavia ItalyPatrizia Noris, University of Pavia Internal Medicine, IRCCS Policlinico San Matteo Foundation Pavia ItalyEdoardo Ascari, University of Pavia Internal Medicine, IRCCS Policlinico San Matteo Foundation Pavia ItalyThe Italian TTP Study Group Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Acquired Hb H disease associated with elevated Hb F level in patient affected by primary myelofibrosis

Acquired Hb H disease associated with elevated Hb F level in patient affected by primary myelofibrosis Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0878-4Authors Ciro Roberto Rinaldi, University Federico II Hematology Division, Department of Biochemistry and Medical Biotechnology 80131 Naples ItalyPaola Rinaldi, University Federico II Hematology Division, Department of Biochemistry and Medical Biotechnology 80131 Naples ItalyFabrizio Pane, University Federico II Hematology Division, Department of Biochemistry and Medical Biotechnology 80131 Naples ItalyAndrea Camera, University Federico II Hematology Division, Department of Biochemistry and Medical Biotechnology 80131 Naples ItalyCarmine Rinaldi, Laboratorio di Biologica Molecolare P.O. Marcianise ASL Caserta Caserta Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Imatinib, cytokines and interstitial lung disease in a patient with primary myelofibrosis

Imatinib, cytokines and interstitial lung disease in a patient with primary myelofibrosis Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0884-6Authors Bruno Robibaro, Medical University Vienna Division of Pulmonary Medicine Waehringer Guertel 18-20 1090 Vienna AustriaAnna Kropfmueller, Medical University Vienna Division of Pulmonary Medicine Waehringer Guertel 18-20 1090 Vienna AustriaMathias Prokop, University Medical Center Utrecht Department of Radiology Heidelberglaan 100 3584 CX Utrecht The NetherlandsPaul Haber, Medical University Vienna Division of Pulmonary Medicine Waehringer Guertel 18-20 1090 Vienna AustriaHeinz Gisslinger, Medical University Vienna Division of Hematology and Blood Coagulation Waehringer Guertel 18-20 1090 Vienna Austria Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Pulmonary marginal zone B-cell lymphoma of MALT type—What is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) Study

Abstracts Pulmonary marginal zone B-cell lymphoma of the MALT type (P-MZL) is a relatively rare form of lymphoma. We conducted a retrospective analysis of the clinical features and treatment outcomes of P-MZL for the evaluation of prognostic factors, and to collect information about the optimal treatment modality for this condition. From 1991 to 2008, a total of 61 patients with biopsy-confirmed P-MZL were retrospectively analyzed. The median age of our subjects was 60 (range, 34–79) years. Twenty-five of the patients (41%) were initially diagnosed without any symptoms. Video-assisted thoracic surgery was utilized for diagnosis in 19 patients (31%). Thirty-eight patients' conditions (62%) involved a single lobe. Lung lesions were bilateral in 15 patients (25%). Eleven patients evidenced synchronous involvement of extra-pulmonary site MZL. Overall, 56 of 61 patients were treated with surgery (n = 22), chemotherapy (n = 28), or radiotherapy (n = 6). Among them, 46 patients achieved complete or partial remission. The median time to progression (TTP) was 5.6 (95% CI, 2.6–8.6) years. Five patients died during follow-up. Extra-pulmonary MZL and LN involvement were shown to be poor prognostic factors for TTP. We noted no differences between the operation group and chemotherapy group in terms of TTP. P-MZL tends to be an indolent disease—characterized by prolonged survival with frequent relapses. This is similar to what is observed with other cases of MALT-type site MZL. In order to conserve lung function and reduce the risks of operation, chemotherapy should be considered as a first-line option for the treatment of P-MZL. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0875-7Authors Sung Yong Oh, Dong-A University College of Medicine Department of Internal Medicine 3-1 Dongdaeshin-dong Seo-gu Busan 602-715 KoreaWon Seog Kim, Sungkyunkwan University School of Medicine Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center Seoul KoreaJin Seok Kim, Sungkyunkwan University School of Medicine Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center Seoul KoreaSeok Jin Kim, Yonsei University College of Medicine Department of Internal Medicine Seoul KoreaHyuk-Chan Kwon, Dong-A University College of Medicine Department of Internal Medicine 3-1 Dongdaeshin-dong Seo-gu Busan 602-715 KoreaDae Ho Lee, University of Ulsan College of Medicine Department of Internal Medicine, Asan Medical Center Seoul KoreaJong Ho Won, University College of Medicine, Soon Chun Hyang University Department of Internal Medicine Seoul KoreaIn Gyu Hwang, Chung-Ang University Division of Hematology–Oncology, Department of Medicine Seoul KoreaMin Kyoung Kim, Yeungnam University College of Medicine Division of Oncology, Department of Internal Medicine Daegu KoreaSoon Il Lee, Dankook University College of Medicine Department of Internal Medicine Cheonan KoreaYee Soo Chae, Kyungpook National University Hospital, Kyungpook National University School of Medicine Department of Hematology/Oncology Daegu KoreaDeok-Hwan Yang, Chonnam National University Hwasun Hospital Department of Hematology–Oncology Jeollanam-do KoreaGyeong-Won Lee, College of Medicine, Gyeongsang National University Division of Hematology–Oncology, Department of Internal Medicine Jinju KoreaChul Won Choi, Korea University Anam Hospital, Korea University College of Medicine Division of Oncology -Hematology, Department of Internal Medicine Seoul KoreaJinny Park, Gachon Medical School Department of Internal Medicine Inchon KoreaCheolwon Suh, University of Ulsan College of Medicine Department of Internal Medicine, Asan Medical Center Seoul KoreaHyo-Jin Kim, Dong-A University College of Medicine Department of Internal Medicine 3-1 Dongdaeshin-dong Seo-gu Busan 602-715 Korea Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

CTLA-4 +49A>G polymorphism of recipients of HLA-matched sibling allogeneic stem cell transplantation is associated with survival and relapse incidence

Abstract Conflicting observations have been reported about the role of CTLA-4 gene polymorphisms in the clinical outcome of allogeneic hematopoietic stem cell transplantation (HSCT). We have investigated three polymorphisms of the CTLA-4 gene (−318C>T, +49A>G, CT60G>A) in 133 donor/recipient pairs who underwent HLA-matched sibling donor HSCT for hematological malignancies. We found no association of the clinical outcome of the HSCT with either recipient or donor −318C>T and CT60G>A polymorphisms. At variance, we found a significant association of donor +49A>G G/G genotype with longer overall survival (OS; log-rank test, P = 0.04), and the number of +49A>G G-alleles in the recipient with longer OS (P = 0.027), longer disease-free survival (P = 0.036) and reduced relapse rate (P = 0.042). However, only recipient +49A>G polymorphism was retained as independent prognostic factor in a multivariate analysis, suggesting that the expression of CTLA-4 on the cells of recipient may be relevant for the clinical outcome of HSCT. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0885-5Authors Patrizia Piccioli, National Cancer Research Institute Medical Oncology C Genoa ItalyGiuseppe Balbi, University of Genoa Department of Oncology, Biology and Genetics Genoa ItalyMartina Serra, National Cancer Research Institute Medical Oncology C Genoa ItalyAnna Morabito, National Cancer Research Institute Breast Cancer Laboratory of Tumour Genetics Unit L.go R. Benzi 10 16132 Genoa ItalyTeresa Lamparelli, San Martino Hospital Division of Hematology Genoa ItalyMarco Gobbi, University of Genoa Department of Hematology and Oncology Genoa ItalyStefania Laurent, National Cancer Research Institute Breast Cancer Laboratory of Tumour Genetics Unit L.go R. Benzi 10 16132 Genoa ItalyBeatrice Dozin, National Cancer Research Institute Clinical Epidemiology Unit Genoa ItalyPaolo Bruzzi, National Cancer Research Institute Clinical Epidemiology Unit Genoa ItalyAnna Maria Ferraris, University of Genoa and National Cancer Research Institute Genoa ItalyAndrea Bacigalupo, San Martino Hospital Division of Hematology Genoa ItalyRosario Notaro, Istituto Toscano Tumori (CRL-ITT) Laboratory of Genetics and Gene Transfer, Core Research Laboratory Florence ItalyMaria Pia Pistillo, National Cancer Research Institute Breast Cancer Laboratory of Tumour Genetics Unit L.go R. Benzi 10 16132 Genoa Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

The role of chemokines in B cell chronic lymphocytic leukaemia: pathophysiological aspects and clinical impact

Abstract Chemokines are centrally involved in leukocyte migration, homing and haematopoiesis. Besides these physiological aspects, their role in pathological processes especially with respect to solid tumour and haematological neoplasias is well established. In this context, the focus was set here on disclosing their contribution in B cell chronic lymphocytic leukaemia (B-CLL), which is regarded as the most characteristic low-grade lymphoma. Up to now, it has been demonstrated that several chemokines are involved in migration of B-CLL cells to lymph nodes, secondary lymphoid organs and bone marrow. Moreover, some chemokines are known to have an anti-apoptotic effect and thus contribute to the survival of B-CLL cells. By interfering with both of these aspects, new therapeutic targets for this yet incurable disease may be developed. Furthermore, a correlation can be drawn between the concentration of some chemokines in patients’ serum, the expression of their respective receptors on B-CLL cells and well-established predictive clinical parameters. Consequently, further systematic investigation of the chemokine network may lead to the identification of new diagnostic and prognostic markers. This review focuses on the impact of chemokines and their receptors on B-CLL pathophysiology and points out potential implications for both treatment and diagnosis. Content Type Journal ArticleCategory Review ArticleDOI 10.1007/s00277-009-0876-6Authors Percy Schröttner, University Clinic of Freiburg, Department of Hematology and Oncology Hugstetterstr. 55 79106 Freiburg GermanyMarion Leick, University Clinic of Freiburg, Department of Hematology and Oncology Hugstetterstr. 55 79106 Freiburg GermanyMeike Burger, University Clinic of Freiburg, Department of Hematology and Oncology Hugstetterstr. 55 79106 Freiburg Germany Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Absence of cardiac siderosis despite hepatic iron overload in Italian patients with thalassemia intermedia: an MRI T2* study

Abstract Cardiac involvement in patients with thalassemia intermedia (TI) is characterized by a high-output state and pulmonary hypertension, with systolic left ventricle function usually being preserved. Myocardial iron overload in patients with TI has not been extensively studied. We conducted a cross-sectional study of 49 Italian patients with TI. Patient charts were reviewed and data collected for transfusion and iron chelation history, status of the spleen, and comorbid illnesses or infections. Blood samples were obtained for assessment of hemoglobin, serum ferritin, and liver enzyme levels. Doppler echocardiography was done for all patients. Cardiac and hepatic iron levels were measured by magnetic resonance imaging T2*. The mean age was 40.5 ± 8.3 years, with a male to female ratio of 29:20. A total of 34 (69.4%) patients were splenectomized, and four patients had evidence of hepatitis C infection. Around 45% of patients were transfusion naïve while the rest received infrequent (47%) or regular (8%) transfusions. A total of 31 (63.3%) patients were maintained on iron chelation therapy. None of the patients had evidence of heart failure. Mean serum ferritin and liver iron concentration were 1,060.2 ng/ml and 8.2 mg Fe per gram dry weight, respectively. None of the patients had evidence of cardiac iron overload (mean cardiac T2* = 38.7 ± 11.0 ms). There were no statistically significant correlation between cardiac T2* values and liver iron concentration, serum ferritin, or any patient, disease, or treatment-related parameters. Patients with TI show absence of cardiac iron overload even if hepatic iron accumulation is significant. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0879-3Authors Alberto Roghi, Niguarda Ca’ Granda Hospital Cardiac MR Unit, De Gasperis’ Department of Cardiology Milan ItalyMaria Domenica Cappellini, Universitá di Milano Policlinico Foundation IRCCS Milan ItalyJohn C. Wood, University of Southern California Divisions of Pediatric Cardiology and Radiology, Children’s Hospital Los Angeles and Keck School of Medicine Los Angeles CA USAKhaled M. Musallam, American University of Beirut Medical Center Department of Internal Medicine, Hematology–Oncology Division Beirut LebanonPedrotti Patrizia, Niguarda Ca’ Granda Hospital Cardiac MR Unit, De Gasperis’ Department of Cardiology Milan ItalyMaria Rosaria Fasulo, Universitá di Milano Policlinico Foundation IRCCS Milan ItalyClaudia Cesaretti, Universitá di Milano Policlinico Foundation IRCCS Milan ItalyAli T. Taher, American University of Beirut Medical Center Department of Internal Medicine, Hematology–Oncology Division Beirut Lebanon Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Monoclonal gammopathy of undetermined significance related pyoderma gangrenosum successfully treated with autologous peripheral blood stem cell transplantation

Monoclonal gammopathy of undetermined significance related pyoderma gangrenosum successfully treated with autologous peripheral blood stem cell transplantation Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0880-xAuthors Ching-Ming Chang, Taichung Veterans General Hospital Division of Hematology/Oncology, Department of Medicine 160, Section 3, Chungkang Road Taichung 407 Taiwan Republic of ChinaWen-Lee Hwang, Taichung Veterans General Hospital Division of Hematology/Oncology, Department of Medicine 160, Section 3, Chungkang Road Taichung 407 Taiwan Republic of ChinaZu-Yi Hsieh, Taichung Veterans General Hospital Division of Immunology, Department of Medicine Taichung Taiwan Republic of ChinaRen-Ching Wang, Taichung Veterans General Hospital Department of Pathology Taichung Taiwan Republic of ChinaChieh-Lin Teng, Taichung Veterans General Hospital Division of Hematology/Oncology, Department of Medicine 160, Section 3, Chungkang Road Taichung 407 Taiwan Republic of China Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

The clinicopathological analysis of 303 cases with malignant lymphoma classified according to the World Health Organization classification system in a single institute of Taiwan

Abstract Several reports have shown a different distribution of malignant lymphoma (ML) in Asian and Western populations. The purpose of our survey was to elucidate whether there are substantial differences in the frequencies of subtypes of ML between different geographical areas. All entities diagnosed as ML between June 1995 and December 2007 were selected according to the 2008 World Health Organization (WHO) classification and searched for clinical outcomes. The cases were retrieved and reviewed by a panel of clinical haematologists and haematopathologists. A total of 303 patients with ML were identified for retrospective analysis. Of the 303 patients with ML, 278 patients (91.7%) had non-Hodgkin’s lymphoma (NHL), and 25 (9.2%) had Hodgkin’s lymphoma. Of the 278 patients with NHL, 223 (73.6%) had lymphoma of B-cell lineage, and 55 (18.1%) had lymphoma of T-cell lineage. One hundred and thirty-seven patients were diagnosed with diffuse large B-cell lymphoma, which was the most common B-cell lineage subtype and accounted for 45.2% of patients with NHL. Peripheral T-cell lymphomas were the most frequent subset of the T-cell neoplasms, comprising 10.6% of ML. Extranodal involvement was found in 125 (44.9%) of the 278 patients with NHL, and the lymph node was the site of primary involvement in 153 patients (55.1%). Fifty-nine (47.2%) of the 125 patients with extranodal presentation had gastrointestinal tract involvement. Outcome was worse in patients with extranodal NHL than in those with nodal NHL through the entire follow-up period; the difference in survival rates was significant. Our findings clarify the applicability and prognostic relevance of the WHO classification system and provide further information about the incidence of various lymphoma subtypes in Taiwan. Primary extranodal NHL was associated with a worse prognosis and distinct characteristics compared with nodal NHL. The outcome of different types of extranodal NHL should be investigated further. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0870-zAuthors Wei-Liang Chen, Tri-Service General Hospital, National Defense Medical Center Division of Hematology, Department of Medicine Number 325, Section 2, Cheng-Kung Road, Neihu 114 Taipei TaiwanWen-Chiuan Tsai, Tri-Service General Hospital, National Defense Medical Center Department of Pathology Taipei TaiwanTsu-Yi Chao, Tri-Service General Hospital, National Defense Medical Center Division of Hematology, Department of Medicine Number 325, Section 2, Cheng-Kung Road, Neihu 114 Taipei TaiwanLai-Fa Sheu, Tri-Service General Hospital, National Defense Medical Center Department of Pathology Taipei TaiwanJung-Mao Chou, Tri-Service General Hospital, National Defense Medical Center Department of Pathology Taipei TaiwanWoei-Yau Kao, Tri-Service General Hospital, National Defense Medical Center Division of Hematology, Department of Medicine Number 325, Section 2, Cheng-Kung Road, Neihu 114 Taipei TaiwanYeu-Chin Chen, Tri-Service General Hospital, National Defense Medical Center Division of Hematology, Department of Medicine Number 325, Section 2, Cheng-Kung Road, Neihu 114 Taipei TaiwanChing-Liang Ho, Tri-Service General Hospital, National Defense Medical Center Division of Hematology, Department of Medicine Number 325, Section 2, Cheng-Kung Road, Neihu 114 Taipei Taiwan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Short and long-term outcome of treatment with high-dose melphalan and stem cell transplantation for multiple myeloma-associated AL amyloidosis

Abstract High-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation (HDM/SCT) has been shown to result in a durable hematologic response and prolonged overall survival in systemic amyloid light-chain (AL) amyloidosis as well as multiple myeloma. However, little is known about the myeloma associated with AL amyloidosis (MM/AL). In this retrospective study, we evaluated 87 patients with MM/AL from 1994 to 2007. Sixteen of these patients underwent HDM/SCT at Boston University Medical Center. Three patients (19%) died from treatment-related mortality. The overall median survival for all 87 patients was 22 months by Kaplan–Meier estimates. However, this was improved to 54.5 months for those who received HDM/SCT compared to 21 months for those who did not receive HDM/SCT. A hematologic complete response was achieved by 25% (4/16) of patients at 6 months after HDM/SCT. Hematologic relapses occurred in 60% of patients at a median of 1 year after HDM/SCT. In conclusion, HDM/SCT can prolong overall survival in patients with MM/AL who are eligible to receive it. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0874-8Authors Saulius Girnius, Boston University School of Medicine Amyloid Treatment and Research Program Boston MA USADavid C. Seldin, Stem Cell Transplantation Program of the Section of Hematology-Oncology FGH 1007, 820 Harrison Avenue Boston MA 02118 USAMartha Skinner, Boston University School of Medicine Amyloid Treatment and Research Program Boston MA USAKathleen T. Finn, Stem Cell Transplantation Program of the Section of Hematology-Oncology FGH 1007, 820 Harrison Avenue Boston MA 02118 USAKaren Quillen, Stem Cell Transplantation Program of the Section of Hematology-Oncology FGH 1007, 820 Harrison Avenue Boston MA 02118 USAGheorghe Doros, Boston University School of Medicine Amyloid Treatment and Research Program Boston MA USAVaishali Sanchorawala, Stem Cell Transplantation Program of the Section of Hematology-Oncology FGH 1007, 820 Harrison Avenue Boston MA 02118 USA Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Hematoma of the iliopsoas muscle due to thrombocytopenia resulting from the administration of a third-generation cephalosporin

Hematoma of the iliopsoas muscle due to thrombocytopenia resulting from the administration of a third-generation cephalosporin Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0872-xAuthors Makoto Onodera, Iwate Medical University Department of Critical Care Medicine 19-1 Uchimaru Morioka City Iwate 020-8505 JapanYasuhisa Fujino, Iwate Medical University Department of Critical Care Medicine 19-1 Uchimaru Morioka City Iwate 020-8505 JapanYoshihiro Inoue, Iwate Medical University Department of Critical Care Medicine 19-1 Uchimaru Morioka City Iwate 020-8505 JapanSatoshi Kikuchi, Iwate Medical University Department of Critical Care Medicine 19-1 Uchimaru Morioka City Iwate 020-8505 JapanShigeatsu Endo, Iwate Medical University Department of Critical Care Medicine 19-1 Uchimaru Morioka City Iwate 020-8505 Japan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Bortezomib, thalidomide, dexamethasone induction therapy followed by melphalan, prednisolone, thalidomide consolidation therapy as a first line of treatment for patients with multiple myeloma who are non-transplant candidates: results of the Korean Multiple Myeloma Working Party (KMMWP)

Abstract Bortezomib (VELCADE®), thalidomide and dexamethasone (VTD), as well as melphalan, prednisolone, and thalidomide (MPT) therapy, are highly effective in patients with multiple myeloma. We evaluated the responses and survival times of 35 patients treated with VTD followed by MPT. All patients were newly diagnosed and non-transplantation candidates. Patients received six cycles of VTD, which were followed by eight cycles of MPT. Approximately 97% of patients exhibited early responses to therapy, as early as the second cycle of VTD. Thirty percent of the responses were high quality, which was defined as a complete response (CR), a near-CR or a very good partial response. High-risk patients were defined as patients with any of the following aberrations: del(13), t(4;14), or del(17p). The remaining patients were defined as standard risk. Eleven high-risk patients showed 100% response rates, including 91% high-quality responses. In contrast, 13 standard-risk patients exhibited 92% response rates, including 61% high-quality responses. The overall 2-year survival rates were 60% in high-risk patients and 85% in standard-risk patients, which was not significantly different. As a first-line therapy, VTD followed by MPT has the potential to provide high-quality responses with durable remission among elderly and high-risk patients (clinicaltrials.gov identifier: NCT00320476). Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0871-yAuthors Hyeon-Seok Eom, National Cancer Center Hematology-Oncology Clinic, Center for Specific Organs Cancer Goyang South KoreaYeo-Kyeoung Kim, Chonnam National University Hwasun Hospital Hematology-Oncology Jeollanam-do South KoreaJoo-Seop Chung, Pusan National University Hospital Hematology-Oncology Busan South KoreaKihyun Kim, Sungkyunkwan University School of Medicine, Samsung Medical Center Hematology/Oncology, Department of Medicine Seoul South KoreaHyo Jung Kim, Hallym University Medical Center Hematology-Oncology Anyang South KoreaHo Young Kim, Hallym University Medical Center Hematology-Oncology Anyang South KoreaJong-Youl Jin, Holy Family Hospital Hemato-Oncology Bucheon South KoreaYoung-Rok Do, Dongsan Medical Center Hematology-Oncology Daegu South KoreaSuk-Joong Oh, Samsung Medical Center, Sungkyunkwan University School of Medicine Division of Hematology-Oncology Seoul South KoreaCheolwon Suh, University of Ulsan College of Medicine Oncology, Asan Medical Center Seoul South KoreaChu-Myong Seong, Ewha Woman’s University Hospital Hemato-Oncology Seoul South KoreaChul Soo Kim, Inha University Hospital Comprehensive Cancer Center Incheon South KoreaDong Soon Lee, Seoul National University Hospital Laboratory Medicine Seoul South KoreaJae Hoon Lee, Gachon University Gil Hospital Department of Hematology-Oncology Incheon 405-760 South Korea Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Bortezomib-based therapy as induction regimen of an autograft program in front-line treatment of multiple myeloma with end-stage renal disease

Bortezomib-based therapy as induction regimen of an autograft program in front-line treatment of multiple myeloma with end-stage renal disease Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0867-7Authors Agostina Siniscalchi, “Tor Vergata” University Department of Hematology, S. Eugenio Hospital Piazzale dell’Umanesimo, 10 00100 Rome ItalyTeresa Dentamaro, “Tor Vergata” University Department of Hematology, S. Eugenio Hospital Piazzale dell’Umanesimo, 10 00100 Rome ItalyAlessio Perrotti, “Tor Vergata” University Department of Hematology, S. Eugenio Hospital Piazzale dell’Umanesimo, 10 00100 Rome ItalyPaola Tatangelo, S. Eugenio Hospital Department of Nephrology Rome ItalyPaolo de Fabritiis, “Tor Vergata” University Department of Hematology, S. Eugenio Hospital Piazzale dell’Umanesimo, 10 00100 Rome ItalyTommaso Caravita, “Tor Vergata” University Department of Hematology, S. Eugenio Hospital Piazzale dell’Umanesimo, 10 00100 Rome Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Imatinib and cardiac failure in idiopathic hypereosinophilic syndrome

Imatinib and cardiac failure in idiopathic hypereosinophilic syndrome Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0866-8Authors Lisa Pieri, University of Florence UF di Ematologia, Dip. Area Critica Florence ItalyAlberto Bosi, University of Florence UF di Ematologia, Dip. Area Critica Florence ItalyAlessandro M. Vannucchi, University of Florence UF di Ematologia, Dip. Area Critica Florence Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Acquired factor XIII inhibitor in monoclonal gammopathy of undetermined significance: characterization and cross-linked fibrin ultrastructure

Acquired factor XIII inhibitor in monoclonal gammopathy of undetermined significance: characterization and cross-linked fibrin ultrastructure Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0868-6Authors Yunya Luo, Central South University Division of Hematology, Institute of Molecular Hematology, Second Xiang-ya Hospital Changsha Hunan 410011 People’s Republic of ChinaGuangsen Zhang, Central South University Division of Hematology, Institute of Molecular Hematology, Second Xiang-ya Hospital Changsha Hunan 410011 People’s Republic of ChinaWenli Zuo, Central South University Division of Hematology, Institute of Molecular Hematology, Second Xiang-ya Hospital Changsha Hunan 410011 People’s Republic of ChinaWenli Zheng, Central South University Division of Hematology, Institute of Molecular Hematology, Second Xiang-ya Hospital Changsha Hunan 410011 People’s Republic of ChinaChongwen Dai, Central South University Division of Hematology, Institute of Molecular Hematology, Second Xiang-ya Hospital Changsha Hunan 410011 People’s Republic of China Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

BAALC is an important predictor of refractoriness to chemotherapy and poor survival in intermediate-risk acute myeloid leukemia (AML)

Abstract We have analyzed brain and acute leukemia, cytoplasmic (BAALC) gene expression and other genetic markers (ERG, EVI1, MN1, PRAME, WT1, FLT3, and NPM1 mutations) in 127 intermediate-risk acute myeloid leukemia (AML) patients: 98 cytogenetically normal and 29 with intermediate-risk cytogenetic alterations. High versus low BAALC expressers showed a higher refractoriness to induction treatment (31% vs 10%; p = .005), lower complete remission rate after salvage therapy (82% vs 97%; p = .010), and lower 3-year overall (23% vs 58%, p < .001) and relapse-free survival (26% vs 52%, p = .006). Similar results were found when cytogenetic subgroups were analyzed separately. Multivariate models confirmed the unfavorable prognosis of this marker. In conclusion, BAALC is a relevant prognostic marker in intermediate-risk AML. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0864-xAuthors Carlos Santamaría, Hospital Universitario Salamanca SpainMaría C. Chillón, Hospital Universitario Salamanca SpainRamón García-Sanz, Hospital Universitario Salamanca SpainCristina Pérez, Hospital Clínico San Carlos Madrid SpainMaría D. Caballero, Hospital Universitario Salamanca SpainMaría V. Mateos, Hospital Universitario Salamanca SpainFernando Ramos, Complejo Hospitalario de León and Ibiomed León SpainAlfonso García de Coca, Hospital Clínico de Valladolid Valladolid SpainJosé M. Alonso, Hospital Río Carrión de Palencia Palencia SpainPilar Giraldo, Hospital Miguel Servet Zaragoza SpainTeresa Bernal, Hospital Central de Asturias Oviedo SpainJosé A. Queizán, Hospital General de Segovia Segovia SpainJuan N. Rodríguez, Hospital Juan Ramón Jiménez Huelva SpainNoemí Puig, Hospital Universitario Salamanca SpainAna Balanzategui, Hospital Universitario Salamanca SpainMaría E. Sarasquete, Hospital Universitario Salamanca SpainMiguel Alcoceba, Hospital Universitario Salamanca SpainJoaquín Díaz-Mediavilla, Hospital Clínico San Carlos Madrid SpainJesús San Miguel, Hospital Universitario Salamanca SpainMarcos González, Hospital Universitario Salamanca Spain Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Congenital factor XIII deficiency caused by two mutations in eight Tunisian families: molecular confirmation of a founder effect

Abstract Inherited factor XIII (FXIII) deficiency is a rare bleeding disorder characterized by an umbilical bleeding during the neonatal period, delayed soft tissue bruising, mucosal bleeding spontaneous intracranial hemorrhage, and soft tissue hemorrhages. Congenital FXIII deficiency is an autosomal recessive disorder, usually attributed to a defect in the FXIIIA and B subunits coding, respectively, by F13A and F13B genes. The aim of this study was to determine the molecular defects responsible for congenital factor XIII deficiency in eight Tunisian families. Molecular analysis was performed by direct DNA sequencing of polymerase chain reaction amplified fragments spanning the coding regions and splice junctions of the FXIIIA subunit gene (F13A) in probands and in families' members and compared with the reported sequence of this gene. In all patients, FXIIIA activity was undetectable and the FXIIIB was within the normal range. Direct sequencing of the F13A gene in all probands showed two mutations: the c.869insC mutation found in eight patients and the c.1226G > A transition found in only one. We also confirmed the presence of a founder effect for the first frequent mutation by using two microsatellite markers, HUMF13A01 and a generated ployAC marker (HUMF13A02). We describe here molecular abnormalities found in nine Tunisian probands diagnosed with FXIIIA deficiency. The identification of the founder mutation and polymorphisms allowed a genetic counseling in relatives of these families, and the antenatal diagnosis is now available. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0863-yAuthors Nacim Louhichi, Faculty of Medicine of Sfax Human Molecular Genetic Laboratory Avenue Magida Boulila 3029 Sfax TunisiaMoez Medhaffar, Hédi Chaker de Sfax Service of Hematology. C.H.U Sfax TunisiaIkhlass HadjSalem, Faculty of Medicine of Sfax Human Molecular Genetic Laboratory Avenue Magida Boulila 3029 Sfax TunisiaEmna Mkaouar-Rebai, Faculty of Medicine of Sfax Human Molecular Genetic Laboratory Avenue Magida Boulila 3029 Sfax TunisiaNourhene Fendri-Kriaa, Faculty of Medicine of Sfax Human Molecular Genetic Laboratory Avenue Magida Boulila 3029 Sfax TunisiaHouda Kanoun, Faculty of Medicine of Sfax Human Molecular Genetic Laboratory Avenue Magida Boulila 3029 Sfax TunisiaFiras Yaïch, Faculty of Medicine of Sfax Human Molecular Genetic Laboratory Avenue Magida Boulila 3029 Sfax TunisiaTawfik Souissi, Hédi Chaker de Sfax Service of Hematology. C.H.U Sfax TunisiaMoez Elloumi, Hédi Chaker de Sfax Service of Hematology. C.H.U Sfax TunisiaFaiza Fakhfakh, Faculty of Medicine of Sfax Human Molecular Genetic Laboratory Avenue Magida Boulila 3029 Sfax Tunisia Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Salvage treatment with upfront melphalan 100 mg/m2 and consolidation with novel drugs for fulminant progression of multiple myeloma

Abstract Patients (pts) with fulminant progression (FPG) of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) have poor prognosis. Pancytopenia, extramedullary disease, and/or renal impairment are often present, and treatment options are limited. We have retrospectively evaluated 31 pts with FPG of MM after ASCT who were treated upfront salvage therapy with melphalan 100 mg/m2 (MEL 100) followed by PBSC support and consolidation therapy using regimens containing thalidomide (n = 16) or bortezomib (n = 15). The overall response rate (ORR) was 58% (18/31). After MEL 100, one patient achieved complete remission (3%), 26% of pts very good partial remission, 29% of pts partial remission, and 42% of pts stable disease. Progression within 3 months after MEL 100 occurred in 35% of pts. The median follow-up from MEL 100 was 8 months. The median TTP was 5 months (range, 2–15 months), and the median OS was 8 months (range, 3–23 months). There were no treatment-related deaths. In fulminant progression of MM, upfront MEL 100 is a safe salvage regimen with good response rate (ORR, 58%). Treatment with upfront MEL 100 followed by a thalidomide- or bortezomib-based regimen can prolong overall survival to more than 12 months in 33% of pts with fulminant progression of MM. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0862-zAuthors Marta Krejci, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicZdenek Adam, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicTomas Buchler, Thomayer University Hospital 1st Faculty of Medicine, Department of Oncology Prague Czech RepublicAndrea Krivanova, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicLudek Pour, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicLenka Zahradova, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicMichal Holanek, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicViera Sandecka, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicJiri Mayer, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicJiri Vorlicek, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech RepublicRoman Hajek, Masaryk University Hospital Department of Internal Medicine–Hematooncology Jihlavska 20 Brno 625 00 Czech Republic Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study

Abstract The clinical efficacy and safety of a four-drug combination of bortezomib, cyclophosphamide, thalidomide, and dexamethasone was assessed for patients with relapsed or refractory multiple myeloma. Seventy patients received at least two cycles of treatment with bortezomib 1.3 mg/m2 intravenously on days 1, 4, 8, and 11; cyclophosphamide 150 mg/m2 orally on days 1–4; thalidomide 50 mg/day orally every day; and dexamethasone 20 mg/m2 intravenously on days 1, 4, 8, and 11. The overall best response rate was 88%, with 46% complete response, 9% very good partial response, and 33% partial response. After a median follow-up of 12.6 months, the median progression-free survival (PFS) was 14.6 months with a 3-year PFS of 14% and the median overall survival (OS) was 31.6 months with a 3-year OS of 47%. Grade 3 or 4 adverse events included thrombocytopenia (12%), neutropenia (4%), peripheral sensory neuropathy (3%), with thrombosis being very rare (<1%). Bortezomib combined with cyclophosphamide, thalidomide, and dexamethasone is a highly effective salvage therapy with manageable toxicity for patients with relapsed or refractory multiple myeloma. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0856-xAuthors Yeo-Kyeoung Kim, Chonnam National University Medical School Gwangju Republic of KoreaSang-Kyun Sohn, Kyungpook National University Medical School Daegu Republic of KoreaJae-Hoon Lee, Gachon University Incheon Republic of KoreaDeok-Hwan Yang, Chonnam National University Medical School Gwangju Republic of KoreaJoon-Ho Moon, Kyungpook National University Medical School Daegu Republic of KoreaJae-Sook Ahn, Chonnam National University Medical School Gwangju Republic of KoreaHyeoung-Joon Kim, Chonnam National University Medical School Gwangju Republic of KoreaJe-Jung Lee, Chonnam National University Medical School Gwangju Republic of KoreaThe Korean Multiple Myeloma Working Party (KMMWP), Center for Biomedical Human Resources at Chonnam National University The Brain Korea 21 Project Gwangju Republic of Korea Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Erratum to: Results of FLT3 mutation screening and correlations with immunophenotyping in 169 Brazilian patients with acute myeloid leukemia

Erratum to: Results of FLT3 mutation screening and correlations with immunophenotyping in 169 Brazilian patients with acute myeloid leukemia Content Type Journal ArticleCategory ErratumDOI 10.1007/s00277-009-0860-1Authors Antonio R. Lucena-Araujo, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilDanielle L. Souza, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilFabio Morato de Oliveira, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilMariana Tereza Lira Benicio, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilLorena L. Figueiredo-Pontes, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilBarbara A. Santana-Lemos, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilGuilherme A. dos Santos, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilRafael H. Jacomo, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto BrazilAnemari R. Dinarte-Santos, University of São Paulo Department of Genetics, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Av. Bandeirantes, 3900 14048-900 Ribeirão Preto São Paulo BrazilMihoko Yamamoto, Federal University of São Paulo Department of Hematology and Hemotherapy São Paulo BrazilWilson A. Silva-Jr, University of São Paulo Department of Genetics, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Av. Bandeirantes, 3900 14048-900 Ribeirão Preto São Paulo BrazilMaria de Lourdes Chauffaille, Federal University of São Paulo Department of Hematology and Hemotherapy São Paulo BrazilEduardo M. Rego, University of São Paulo Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto Ribeirão Preto Brazil Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555 Journal Volume Volume 89 Journal Issue Volume 89, Number 2 / February, 2010

Hyperlipidemic myeloma: review of 53 cases

Abstract Hyperlipidemic myeloma is a rare and poorly understood variant of multiple myeloma. We report the case of a 53-year-old woman with hyperlipidemic myeloma, skin xanthomas and hyperviscosity syndrome who underwent allogeneic bone marrow transplantation. A comprehensive literature search identified 52 additional cases with plasma cell disease and hyperlipidemia. A detailed analysis revealed several characteristics of these patients as compared to multiple myeloma with normal lipid status: (1) IgA paraprotein was present in the majority (53% vs. 21% in classical multiple myeloma). (2) Skin xanthomas, especially in the palmar creases, elbows, and knees were common (70%). (3) Hyperviscosity syndrome occurred more often (26% vs. 2–6%). While conventional lipid-lowering therapy had only marginal effects, successful anti-myeloma therapy also reduced hyperlipidemia. Analyses of the mechanisms leading to hyperlipidemia documented complexes of paraprotein and lipoprotein in 75% of the 32 cases tested, suggesting an inhibitory role of the paraprotein on lipid degradation. In conclusion, the clinical characteristics, the therapeutic options, and the pathophysiologic mechanisms of hyperlipidemic myeloma are comprehensively reported using the available data from all 53 published cases in the literature. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0849-9Authors Benjamin Misselwitz, University Hospital Zürich Department of Internal Medicine Rämistr. 100 8091 Zürich SwitzerlandJeroen S. Goede, University Hospital Zürich Clinic of Haematology Rämistr. 100 8091 Zürich SwitzerlandBernhard C. Pestalozzi, University Hospital Zürich Clinic of Oncology Rämistr. 100 8091 Zürich SwitzerlandUrs Schanz, University Hospital Zürich Clinic of Haematology Rämistr. 100 8091 Zürich SwitzerlandJörg D. Seebach, University Hospital Zürich Department of Internal Medicine Rämistr. 100 8091 Zürich Switzerland Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Cytogenetic features and prognosis analysis in Chinese patients with myelodysplastic syndrome: a multicenter study

Abstract It has been suggested that Asian and Western myelodysplastic syndrome (MDS) patients have different cytogenetic and prognostic features. In this study, we retrospectively analyzed clinical and cytogenetic data from 435 Chinese adult primary MDS patients. In addition, we evaluated the prognostic value of the World Health Organization classification as well as six prognostic scoring systems in these patients. The median follow-up time was 25.1 months (5.5–53.2). Of the 435 patients, 186 (42.8%) had died and 40 (9.2%) had progressed to acute myeloid leukemia. Multivariate analysis identified older age, higher percent of marrow blasts, and poor-risk IPSS cytogenetics as characteristics associated with worse survival and higher risk of leukemia transformation. Low platelets, hemoglobin, and mean corpuscular volume were independent factors associated only with worse survival. Among the 424 patients in whom the results of cytogenetic analyses were available, 164 (38.7%) showed karyotypic abnormalities. Incidence of trisomy 8 was common but sole del(5q) was rare in Chinese MDS patients. For predicting survival, most scoring systems were meaningful for stratifying patients into different subgroups, with the exception of the WPSS scoring system. For predicting leukemia evolution, the Spanish scoring system was most effective. Patients with RAEB-2 showed different prognoses from those with RAEB-1. However, there was no significant difference in prognoses between patients with refractory cytopenia with multilineage dysplasia (RCMD) from RA or RARS. In summary, this analysis indicated the presence of a different cytogenetic pattern as well as prognostic features in Chinese MDS patients. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0861-0Authors Hong Wang, Huashan Hospital of Fudan University Department of Haematology 12 Wulumuqi Road central Shanghai 200040 ChinaXiaoQin Wang, Huashan Hospital of Fudan University Department of Haematology 12 Wulumuqi Road central Shanghai 200040 ChinaXiaoPing Xu, Huashan Hospital of Fudan University Department of Haematology 12 Wulumuqi Road central Shanghai 200040 ChinaGuoWei Lin, Huashan Hospital of Fudan University Department of Haematology 12 Wulumuqi Road central Shanghai 200040 China Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

ABO discrepancy in an elderly patient with IgA kappa-type multiple myeloma

ABO discrepancy in an elderly patient with IgA kappa-type multiple myeloma Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0858-8Authors So Young Kim, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of KoreaSeung Hwan Oh, Inje University College of Medicine Department of Laboratory Medicine Gaegeum-dong, Busanjin-gu Busan 614-735 Republic of KoreaKyung Sun Park, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of KoreaMin Jin Kim, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of KoreaGayoung Lim, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of KoreaSun Young Cho, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of KoreaHee Joo Lee, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of KoreaJin-Tae Suh, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of KoreaHwi-Joong Yoon, Kyung Hee University School of Medicine Department of Hematology–Oncology 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of KoreaTae Sung Park, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 Republic of Korea Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Jumping translocation involving 1q21 during long-term complete remission of acute myeloid leukemia

Jumping translocation involving 1q21 during long-term complete remission of acute myeloid leukemia Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0855-yAuthors Sumimasa Nagai, University of Tokyo Department of Hematology and Oncology, Graduate School of Medicine 7-3-1, Hongo, Bunkyo-ku Tokyo 1138655 JapanYasuhito Nannya, University of Tokyo Department of Hematology and Oncology, Graduate School of Medicine 7-3-1, Hongo, Bunkyo-ku Tokyo 1138655 JapanTsuyoshi Takahashi, University of Tokyo Department of Hematology and Oncology, Graduate School of Medicine 7-3-1, Hongo, Bunkyo-ku Tokyo 1138655 JapanMineo Kurokawa, University of Tokyo Department of Hematology and Oncology, Graduate School of Medicine 7-3-1, Hongo, Bunkyo-ku Tokyo 1138655 Japan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Acquired erythropoietic protoporphyria

Acquired erythropoietic protoporphyria Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0859-7Authors Daniel Blagojevic, Landesklinikum St. Poelten Karl Landsteiner Institute for Dermatological Research St. Poelten AustriaThomas Schenk, Landesklinikum St. Poelten Department of Internal Medicine I St. Poelten AustriaOskar Haas, Ambulatorium Medgen Vienna AustriaBrigitte Zierhofer, Landesklinikum St. Poelten Karl Landsteiner Institute for Dermatological Research St. Poelten AustriaChristophoros Konnaris, Medical University of Vienna Department of Gynecology and Obstetrics Vienna AustriaFranz Trautinger, Landesklinikum St. Poelten Karl Landsteiner Institute for Dermatological Research St. Poelten Austria Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Resolution of invasive fungal sinusitis in immunocompromised patients: neutrophil count is crucial beside a combined medical and surgical approach

Resolution of invasive fungal sinusitis in immunocompromised patients: neutrophil count is crucial beside a combined medical and surgical approach Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0854-zAuthors Patrizia Zappasodi, Foundation IRCCS Policlinico San Matteo, University of Pavia Division of Haematology 27100 Pavia ItalyMarianna Rossi, Foundation IRCCS Policlinico San Matteo, University of Pavia Division of Haematology 27100 Pavia ItalyCarlo Castagnola, Foundation IRCCS Policlinico San Matteo, University of Pavia Division of Haematology 27100 Pavia ItalyFabio Pagella, Foundation IRCCS Policlinico San Matteo, University of Pavia Department of Otorhinolaryngology Pavia ItalyElina Matti, Foundation IRCCS Policlinico San Matteo, University of Pavia Department of Otorhinolaryngology Pavia ItalyCaterina Cavanna, Foundation IRCCS Policlinico San Matteo, University of Pavia Virology and Microbiology Laboratory, Department of Diagnostic Medicine and Services Pavia ItalyAlessandro Corso, Foundation IRCCS Policlinico San Matteo, University of Pavia Division of Haematology 27100 Pavia ItalyMaurizio Bonfichi, Foundation IRCCS Policlinico San Matteo, University of Pavia Division of Haematology 27100 Pavia ItalyMario Lazzarino, Foundation IRCCS Policlinico San Matteo, University of Pavia Division of Haematology 27100 Pavia Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Amyloid in bone marrow smears of patients affected by multiple myeloma

Abstract Systemic AL amyloidosis is associated with nearly 15% of cases of multiple myeloma, but data on the frequency and significance of amyloid deposits in the bone marrow of patients affected by multiple myeloma without clinical signs of systemic amyloidosis are scanty. Bone marrow smears of 166 unselected patients affected by multiple myeloma (126 at diagnosis and 40 after treatment) were stained with Congo red and studied by transmission and birefringence microscopy. Both focal and diffuse storages were considered positive. Overall, 67 patients were positive and 99 were negative to Congo red and apple-green birefringence. In particular, 51 of the 126 patients studied at diagnosis and 16 of the 40 patients with advanced disease were positive. Seventeen patients were reassessed after a mean follow-up of 32 months (range: 6–91): disappearance of amyloid deposits was verified in three cases, all responsive to bortezomib-based regimens. The preliminary data available suggest that amyloid deposition in the marrow of myeloma patients is frequent, as it can be traced in nearly 40% of cases. We failed to find correlations between bone marrow amyloid deposits and immunoglobulin type, disease stage, plasma cells percentage, hemoglobin, calcium, creatinine, albumin, or β2microglobulin. Significantly higher incidence of moderate/severe peripheral neuropathy was found in patients with marrow amyloid exposed to potentially neurotoxic antineoplastic agents. Further studies and prolonged follow-up are needed to validate our findings and to define possible prognostic aspects. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0857-9Authors Fara Petruzziello, University Federico II Hematology, Department of Biochemistry and Medical Biotechnology Naples ItalyPio Zeppa, University Federico II Department of Anatomopathology and Cytopathology Naples ItalyLucio Catalano, University Federico II Hematology, Department of Biochemistry and Medical Biotechnology Naples ItalyImmacolata Cozzolino, University Federico II Department of Anatomopathology and Cytopathology Naples ItalyGiuseppe Gargiulo, Stazione Zoologica Anton Dhorn Naples ItalyPellegrino Musto, Hematology and Stem Cell Transplantation Unit, IRCCS Rionero in Vulture PZ ItalyFiorella D’Auria, Hematology and Stem Cell Transplantation Unit, IRCCS Rionero in Vulture PZ ItalyVincenzo Liso, Hematology, AOUCP Bari Bari ItalyRita Rizzi, Hematology, AOUCP Bari Bari ItalyNadia Caruso, Hematology Unit, Annunziata Hospital Cosenza ItalyCatello Califano, PO Umberto I Department of Oncology and Hematology Nocera Inferiore ItalyEugenio Piro, Hematology Unit, AO Pugliese-Ciaccio Catanzaro ItalyMaurizio Musso, Oncohematology Unit, Oncology Department La Maddalena Palermo ItalyVincenza Bonanno, Oncohematology Unit, Oncology Department La Maddalena Palermo ItalyAntonietta Pia Falcone, IRCCS Casa Sollievo della Sofferenza Department of Hematology S. Giovanni Rotondo FG ItalySalvatore Tafuto, Oncohematology, PO S.Maria delle Grazie Pozzuoli ItalyFrancesco Di Raimondo, AO Ferrarotto Department of Hematology Catania ItalyMichelino De Laurentiis, University Federico II Department of Endocrinology and Clinical Oncology Naples ItalyFabrizio Pane, University Federico II Hematology, Department of Biochemistry and Medical Biotechnology Naples ItalyLucio Palombini, University Federico II Department of Anatomopathology and Cytopathology Naples ItalyBruno Rotoli, University Federico II Hematology, Department of Biochemistry and Medical Biotechnology Naples Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Splenic artery pseudoaneurysm with rupture by transformed splenic marginal zone B cell lymphoma

Splenic artery pseudoaneurysm with rupture by transformed splenic marginal zone B cell lymphoma Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0851-2Authors Yu-Chung Huang, Taipei Veterans General Hospital Division of Hematology & Oncology, Department of Medicine No. 201, Sec. 2, Shipai Rd Taipei 112 TaiwanZhi-Yi Xie, Taipei Veterans General Hospital Division of Hematology & Oncology, Department of Medicine No. 201, Sec. 2, Shipai Rd Taipei 112 TaiwanHsiou-Shan Tseng, Taipei Veterans General Hospital Department of Radiology No. 201, Sec. 2, Shipai Rd Taipei 112 TaiwanChing-Feng Yang, Taipei Veterans General Hospital Department of Pathology No. 201, Sec. 2, Shipai Rd Taipei 112 TaiwanLiang-Tsai Hsiao, Taipei Veterans General Hospital Division of Hematology & Oncology, Department of Medicine No. 201, Sec. 2, Shipai Rd Taipei 112 Taiwan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Impact of critical care reconfiguration and track-and-trigger outreach team intervention on outcomes of haematology patients requiring intensive care admission

Abstract Patients with haematological disorders have previously been considered to have poor outcomes following admission to intensive care units. Although a number of haematology centres from outside the UK have now demonstrated improved outcomes, the continuing perception of poor outcomes in this patient group continues to adversely affect their chances of being admitted to some intensive care units (ICUs). Over the past 10 years, there have been many advances within the disciplines of both haematology and intensive care medicine. This study was done to assess outcomes and the impact of an early warning scoring system (EWS) and early involvement of ICU outreach teams. One hundred five haematology patients (haematopoietic stem cell transplant (HSCT) or non-HSCT) had 114 admissions to ICU between April 2006 and August 2008 which coincided with hospital-wide implementation of EWS. The survival to ICU discharge was 56 (53%). Thirty-three (33%) patients were alive at 6 months giving a 1-year survival of 31%. Of the 39 HSCT patients, nine were post-autologous and 30 post-allogeneic transplant. The survival to ICU discharge was 22 (56%) with 14 (36%) patients alive at 6 months. One year survival was 36%. Prior to the introduction of EWS and critical care outreach team (2004), survival to ICU discharge was 44% which has increased to 53% (2006–2008). This is despite an increase in mechanical ventilation in 2006–2008 (50%) as compared to 2004 (32%).The improvement in ICU survivorship was even more prominent in HSCT patients (37% in 2004 versus 56% in 2006–2008). There was a trend towards decreasing Acute Physiology and Chronic Health Evaluation scores with time, suggesting appropriate patients being identified earlier and having timely escalation of their treatment. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0853-0Authors Syed W. I. Bokhari, Nottingham University Hospitals—City Campus Department of Clinical Haematology Nottingham UKTalha Munir, Nottingham University Hospitals—City Campus Department of Clinical Haematology Nottingham UKShabeeha Memon, Nottingham University Hospitals—City Campus Department of Clinical Haematology Nottingham UKJenny L. Byrne, Nottingham University Hospitals—City Campus Department of Clinical Haematology Nottingham UKNigel H. Russell, Nottingham University Hospitals—City Campus Department of Clinical Haematology Nottingham UKMartin Beed, Nottingham University Hospitals—City Campus Critical Care Department Nottingham UK Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression

Abstract Lenalidomide consistently induces transfusion independence and complete cytogenetic response in patients with myelodysplastic syndromes with 5q deletion. Only limited information on long-term outcome is currently available. We performed a long-term follow-up analysis of 42 patients with low or intermediate risk myelodysplastic syndromes and 5q deletion treated with lenalidomide. At a median follow-up of 40 months, 58% of the patients achieved an erythroid response and 48% a cytogenetic response. Thirty-six percent of patients progressed into acute myeloid leukaemia. Most of them (87%) acquired chromosome aberrations in addition to the 5q deletion, i.e. underwent clonal evolution during leukaemogenesis. There were no clinical, cytological or cytogenetic markers at study entry that allowed prediction of increased risk of leukaemic transformation. However, erythroid and cytogenetic responders had a significantly decreased risk of progression to acute myeloid leukaemia (p = 0.001 and p = 0.009, respectively) compared to non-responders. Three and 5 years after study entry, the cumulative incidence of acute myeloid leukaemia for patients with a cytogenetic response was 10% and 21%, respectively, and for patients without cytogenetic response, it was 46% and 60%. Patients with del(5q) myelodysplastic syndromes without erythroid or cytogenetic remission after treatment with lenalidomide have a high risk for clonal evolution and acute myeloid leukaemia progression. In refractory, or relapsing, patients, genetic instability and clonal evolution seem to be the driving forces of leukaemic transformation. Regular follow-up investigations of del(5q) myelodysplastic syndrome patients treated with lenalidomide may help to identify patients requiring alternative treatment strategies. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0846-zAuthors Gudrun Göhring, Hannover Medical School Institute of Cell and Molecular Pathology Carl-Neuberg-Str. 1 30625 Hannover GermanyAristoteles Giagounidis, St. Johannes Hospital Department of Haematology, Oncology and Clinical Immunology Duisburg GermanyGuntram Büsche, Hannover Medical School Institute of Pathology Hannover GermanyHans Heinrich Kreipe, Hannover Medical School Institute of Pathology Hannover GermanyMartin Zimmermann, Hannover Medical School Department of Paediatric Haematology/Oncology Hannover GermanyEva Hellström-Lindberg, Karolinska University Hospital Division of Haematology and Centre of Experimental Haematology, Department of Medicine, Karolinska Institutet Stockholm SwedenCarlo Aul, St. Johannes Hospital Department of Haematology, Oncology and Clinical Immunology Duisburg GermanyBrigitte Schlegelberger, Hannover Medical School Institute of Cell and Molecular Pathology Carl-Neuberg-Str. 1 30625 Hannover Germany Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555