Hematology RSS : Gourt

Make Your Mark at Texas Tech, No State Tax, New Medical School, 2nd-Safest Metro, #5185 :: Texas :: Timeline Recruiting

Join this expanding Department of Medicine and a group of academic and highly dedicated physicians during an exciting time of growth. There are opportunities to play a key role in developing the Hematology

West Texas Charm, Big City State Employed, No State Tax with Amazing Sign-On, #3364 :: Texas :: Timeline Recruiting

Enjoy the best of both worlds! In this position you will have the satisfaction of fostering the growth of tomorrows physicians, as well as working in a thriving practice. Be a part of a team that

Northern California, Pacific Coast City of 25K, #2672 :: California :: Timeline Recruiting

Enjoy arts, music festivals and theatre Superb Victorian Architecture Majestic Redwoods Beautiful Ocean Views Local Airport Local State University This charming coastal city is one of Northern

Hem/Onc Needed - Eastern Slopes of the Black Hills :: South Dakota :: Enterprise Medical Service

Regional Cancer Center is seeking a BE/BE Hematology Oncology physician. This hospital based center currently has 2 full time Hem/Oncs and 3 full time Radiation Oncologist. The physicians are employed

Western Kentucky Seeks Hem/Onc Provider :: Kentucky :: Enterprise Medical Service

Large Healthcare System in western KY is seeking a Hem/Onc for their Cancer Center. The Cancer Center is a state of the art facility built in 2005 is equipped with Trilogy and two linear accelerators.

Located 1 hour outside of Columbus :: Ohio :: Enterprise Medical Service

Private Oncology practice is looking for an additional Hem/Onc. This practice currently consist of one physician who is looking for a partner. Call will be shared with 2 other Oncs in the community

Rocky Mount, NC Seeks 3rd Hem/Onc :: North Carolina :: Enterprise Medical Service

Private practice in North Carolina is seeking a 3rd Hem/Onc. This is a multi specialty group made up of 9 physicians, 10 PAs and 1 NP. The Oncology department is equipped with chemotherapy infusion suite

Live and Work in Central Indiana :: Indiana :: Enterprise Medical Service

Hospital owned Cancer Center in Indiana is seeking a Hem/Onc to join their staff. This center currently has 2 Hematologist/Medical Oncologist and 2 Radiation Oncologist on staff. This position is employed

Southern Florida Needs Hem/Onc :: Florida :: Enterprise Medical Service

Hospital in southern FL is seeking a Hem/Onc for their hospital employed MSG. This is a new position within the MSG. Hospital has an infusion center with 4 chemo chairs and Rad/Onc on staff. They also

Call For More Information :: North Carolina :: Medical Search International

A busy hospital located in a beautiful community near Greensboro, NC is seeking a BC/BE Hem/Onc. State license eligibility is acceptable. Fellows are welcomed!! Excellent support staff and coverage.

Upstate NY Seeks Hem/Onc :: New York :: Enterprise Medical Service

Hospital in NY State is seeking a Hem/Onc to join a two person group. This will be an employed position and the hospital will offer a competitive salary, production bonus, full benefits package etc.

Northwest Pennsylvania :: Pennsylvania :: Enterprise Medical Service

Cancer Center in PA is seeking a BE/BC Hematologist/Oncologist to meet growing patient demand in a thriving hospital based practice in the Great Lakes region of Pennsylvania. The hospital just opened

West Central Illinois :: Illinois :: Nationwide Physician Recruitment

NORTHWEST IL - NEAR QUAD CITIES IOWA and PEORIA, IL 3 HOURS FROM CHICAGO: Multispecialty group of 4 (two physicians and two mid-level providers). The physicians are Hematology/Oncology and

Fall River, MA Area :: Massachusetts :: Enterprise Medical Service

Hospital in MA is looking for a Hem/Onc to join their Cancer Center. There are currently 3 other Hem/Oncs and one Nurse Practitioner employed by the center. This center is state of the art and is currently

Oneida County, NY :: New York :: Enterprise Medical Service

Multi-specialty group has one Hem/Onc looking for 2nd. Current doc is not accepting new patients. Very busy practice with large referral base. Onsite infusion center and mid level providers. This

Southern Ohio :: Ohio :: Enterprise Medical Service

Hospital in southern OH is seeking a Hem/Onc for their cancer center. Cancer Center is equipped with 14 infusion stations (5 are private), chemo certified nurses, two radiation oncologist and pharmacist.

Martinsburg :: West Virginia :: Choice Staffing, Inc.

Choice Professional Contracting, Inc./Choice Staffing, Inc. is seeking a full time physician in Hematology/Oncology for a federal health care center. Inpatient and consultation and management of

Nationwide :: Texas :: Physician Referral Network

Physician Referral Network is your best source to learn about the latest practice opportunities. We are not a recruiting firm, so we promise you'll never be pressured to look at or take a position that

Abilene :: Texas :: Millie Nixon, By Appointment Only

Accepting 2010 residents now. State of the Art Facility with brand new 20 chair chemotherapy are seeking a Hematologogy-Oncologist. The Medical Center is one of the only organization to receive

Topeka :: Kansas :: Hospital employment

New Opportunity for Board Certified hematology/oncology physician. Excellent candidate will be board certified; physicians preparing to sit for boards will be considered. Hospital motivated to hire

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

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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, unclassificable, 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.

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.

How would I manage a sample submitted for flow cytometry analysis for suspicious chronic lymphocytic leukaemia

Samples submitted for a suspect of chronic lymphocytic leukemia are the most frequently observed in flow cytometry laboratories. These cases require not only a precise and prompt diagnosis but also an evaluation on the possibility of performing additional prognostic tests. We will propose two sequential flow cytometry panels and a personal opinion on how to manage these samples for both diagnostic and prognostic assessment, taking into account the published guidelines and recommendations. Copyright © 2009 John Wiley & Sons, Ltd.

Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity

Nucleophosmin (NPM) is a ubiquitously expressed chaperone protein that shuttles rapidly between the nucleus and cytoplasm, but predominantly resides in the nucleolus. It plays key roles in ribosome biogenesis, centrosome duplication, genomic stability, cell cycle progression and apoptosis. Somatic mutations in exon 12 of the NPM gene (NPM1) are the most frequent genetic abnormality in adult acute myeloid leukaemia (AML), found in approximately 35% of all cases and up to 60% of patients with normal karyotype (NK) AML. In children, NPM1 mutations are far less frequent, occurring in 8-10% of all AML cases, and in approximately 25% of those with a NK. NPM1 mutations lead to aberrant localization of the NPM protein into the cytoplasm, thus the designation, NPMc+ AML. NPMc+ AML is seen predominantly in patients with a NK and is essentially mutually exclusive of recurrent chromosomal translocations. Patients with NPM1 mutations are twice as likely as those who lack an NPM1 mutation to also have a FMS-like tyrosine kinase (FLT3) internal tandem duplication (ITD) mutation. NPMc+ AML is also characterized by a unique gene expression signature and microRNA signature. NPMc+ AML has important prognostic significance, as NPMc+ AML, in the absence of a coexisting FLT3-ITD mutation, is associated with a favourable outcome. NPM1 mutations have also shown great stability during disease evolution, and therefore represent a possible marker for minimal residual disease detection. Given its distinctive biologic and clinical features and its clear clinical relevance, NPMc+ AML is included as a provisional entity in the 2008 WHO classifications. There is still much to be learned about this genetic alteration, including its exact role in leukaemogenesis, how it interacts with other mutations and why it confers a more favourable prognosis. Further, it represents a potential therapeutic target warranting research aimed at identifying novel small molecules with activity in NPMc+ AML. 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.

Continuous infusion idarubicin and intravenous busulphan as conditioning regimen to autologous stem cell transplantation for patients with acute myeloid leukaemia

The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous (iv) busulfan (Bu) and continuous infusion Idarubicin (IDA) as a conditioning regimen to autologous haematopoietic stem cell transplantation (ASCT) in patients with acute myeloid leukaemia (AML). The protocol included IDA at 20 mg/sqm daily as 3 days continuous infusion (from day -13 to -11) and intravenous BU at 3.2 mg/kg daily from day -5 to -2. Patients aged over 60 years received a reduced schedule (2 days IDA and 3 days BU at the same dose). Twenty-five patients with a median age of 51 years (28-72) were enrolled. All patients received peripheral blood stem cells (PBSC). The median interval between diagnosis and ASCT was 4 months. The median number of CD34+ cells infused was 5.9 × 10E6/kg. The median number of days to PMN >500/cmm and platelets >20000/cmm was 10 and 13, respectively. In order to perform a comparison in terms of haematological and non haematological toxicity, a group of 30 patients, who were previously autografted after conditioning with IDA and oral Bu was considered. Selection of factors for a matched pair analysis included median age, percentage of subjects aged over 60 years, median CD34+ cell received, cytogenetic and molecular findings and per cent of secondary AML. As compared to previous series, the occurrence of severe mucositis was dramatically reduced (80% vs. 12%, p < 0.0001). In addition, need and duration of total parenteral nutrition (TPN), iv antibiotic therapy and hospitalization were also significantly reduced. We conclude that replacement of oral with intravenous BU results in a more favourable toxicity profile. A longer follow-up is required to assess a potential advantage in terms of disease free survival (DFS). 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.

Anaplastic large cell lymphoma: one or more entities among T-cell lymphoma?

Anaplastic large cell lymphoma (ALCL) is a subtype of peripheral T-cell lymphoma (PTCL) first described in 1985 as a lymphoid malignancy characterized by marked cellular pleomorphism, propensity to grow cohesively, tendency to invade lymph node sinuses and diffuse expression of CD30 . The discovery of the t(2;5), involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2 and the nucleophosmin (NPM) gene on chromosome 5 in the majority of systemic ALCL, has soon pointed out that ALCL is a clinically and biologically heterogeneous disease. While ALK-positive (ALK+) ALCL is usually characterized by onset in children and young adults and better prognosis, epidemiology, poor outcome and possibly genetic defects of ALK-negative (ALK-) ALCL suggest that this neoplasms should be considered an independent pathological entity. The aim of this review is to illustrate clinical features, histology, immunophenotype, genetics and biology of ALCL and discuss possible relationship(s) among different T-non-Hodgkin lymphoma (T-NHL). Copyright © 2009 John Wiley & Sons, Ltd.

KHSV- EBV- post-transplant effusion lymphoma with plasmablastic features: variant of primary effusion lymphoma?

Primary effusion lymphoma (PEL) is a rare type of B-cell non-Hodgkin lymphoma (NHL), which predominantly occurs in HIV-infected individuals, and is pathogenetically linked with Kaposi sarcoma (KS)-associated herpes virus/human herpes virus-8 (KSHV/HHV-8) infection with or without evidence of Epstein-Barr virus (EBV) co-infection. Although uncommon, PELs have been reported in immunocompetent patients and recipients of solid organ allografts. Rare cases of KSHV- EBV+ post-transplant effusion lymphomas resembling PEL have also been described, as have KSHV- EBV- effusion lymphomas, the latter including those arising in individuals with chronic liver disease. We report a unique KSHV- EBV- post-transplant effusion lymphoma associated with serum paraproteins, occurring in an HIV- individual, which had cytologic features and phenotype similar to PEL, and displayed a complex karyotype including isochromosome 12p and translocation t(8;22), resulting in rearrangement of c-MYC. Copyright © 2009 John Wiley & Sons, Ltd.

Analysis of Bcr-Abl kinase domain mutations in Korean chronic myeloid leukaemia patients: poor clinical outcome of P-loop and T315I mutation is disease phase dependent

Despite durable responses to imatinib in chronic myeloid leukaemia (CML), mutations in Bcr-Abl kinase domain (KD) are known to induce imatinib resistance and cause poor clinical outcome. We characterized Bcr-Abl KD mutations in 137 Korean CML patients with imatinib resistance (n = 111) or intolerance (n = 26) using allele specific oligonucleotide polymerase chain reaction (PCR) and direct sequencing. Seventy (51%) patients harboured 81 mutations of 20 different types with increasing prevalence in advanced phase. Nine (13%) patients had multiple mutations. No mutation was found in intolerant patients. T315I was the most common mutation and P-loop was the hottest spot in Bcr-Abl KD. Patients harbouring P-loop mutation, T315I, or multiple mutations showed poor overall survival and progression free survival compared with patients harbouring other mutations. Survival analysis according to disease phase of mutation being detected and type of mutations provided correlation between P-loop or T315I mutation and poor overall survival in blast crisis, but not in accelerated phase (AP) or chronic phase (CP), indicating poor clinical outcome of particular mutations depends on disease phase. CML patients with imatinib resistance showed high rate (63%) of mutations in Bcr-Abl KD and therefore CML patients who do not respond to imatinib should be the candidates for mutation screening as molecular monitoring. 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.

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

Serum albumin level is a significant prognostic factor reflecting disease severity in symptomatic multiple myeloma

Abstract Serum albumin level, in association with serum interleukin-6 level, is a significant prognostic factor in multiple myeloma patients. The aim of this study was to determine any clinical factors associated with decreased serum albumin level. We retrospectively reviewed the records of 373 patients diagnosed with multiple myeloma at the Asan Medical Center, Seoul, Korea, between January 1996 and March 2008. Patients were divided into two groups according to serum albumin level (above or below 3.5 g/dL, the prognostic cutoff value), and clinical parameters were compared between groups. We aimed to identify any clinical parameters associated with low serum albumin levels. The group with serum albumin <3.5 g/dL showed older patient age, lower hemoglobin level, and poorer performance status. By contrast, levels of serum beta2-microglobulin, serum M protein, and bone marrow plasma cells were significantly higher in the group with low serum albumin levels. No significant between-group differences were found when serum calcium and creatinine levels were compared. Numbers of cytogenetic abnormalities and lytic bone lesions also showed no significant between-group differences. In both univariate and multivariate analyses, serum albumin level less than 3.5 g/dL was identified as a significant pretreatment prognostic factor. Lower serum albumin levels in multiple myeloma patients are associated with clinical factors reflecting disease severity. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0841-4Authors Jeong Eun Kim, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 86 Asan Byeongwon gil, Songpa-gu Seoul 138-736 South KoreaChanghoon Yoo, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 86 Asan Byeongwon gil, Songpa-gu Seoul 138-736 South KoreaDae Ho Lee, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 86 Asan Byeongwon gil, Songpa-gu Seoul 138-736 South KoreaSang-We Kim, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 86 Asan Byeongwon gil, Songpa-gu Seoul 138-736 South KoreaJung-Shin Lee, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 86 Asan Byeongwon gil, Songpa-gu Seoul 138-736 South KoreaCheolwon Suh, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 86 Asan Byeongwon gil, Songpa-gu Seoul 138-736 South Korea Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

ABO discrepancy in a young Korean serviceman with common variable immunodeficiency

ABO discrepancy in a young Korean serviceman with common variable immunodeficiency Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0840-5Authors Seung Hwan Oh, Inje University Department of Laboratory Medicine, College of Medicine GaeGeum-dong, Busanjin-gu Busan 614-735 South KoreaCheol-In Kang, Sungkyunkwan University School of Medicine Division of Infectious Diseases, Samsung Medical Center 50 Ilwon-dong, Gangnam-gu Seoul 135-710 South KoreaJuwon Kim, Yonsei University College of Medicine Department of Laboratory Medicine 250 Seongsanno, Seodaemun-gu Seoul 120-752 South KoreaTae Sung Park, Kyung Hee University School of Medicine Department of Laboratory Medicine 1 Hoegi-dong, Dongdaemun-gu Seoul 130-702 South Korea Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Plasmablastic crisis of Philadelphia chromosome-positive chronic myeloid leukemia

Plasmablastic crisis of Philadelphia chromosome-positive chronic myeloid leukemia Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0852-1Authors Kalliopi N. Manola, National Center for Scientific Research (NCSR) “Demokritos” Laboratory of Cytogenetics 15310 Aghia Paraskevi Athens GreeceDespina Pantelidou, Medical School AUTH First Department of Internal Medicine, Hematology department Thessaloniki GreeceMaria Papaioannou, Medical School AUTH First Department of Internal Medicine, Hematology department Thessaloniki Greece Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

18F-FDG PET/CT in primary non-Hodgkin's lymphoma of the sinonasal tract

18F-FDG PET/CT in primary non-Hodgkin's lymphoma of the sinonasal tract Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0842-3Authors Adrian Tempescul, CHU Brest Department of Clinical Hematology, Institute of Cancerology and Hematology Avenue Foch 29609 Brest FranceSolene Querellou, CHU Brest Department of Nuclear Medicine Avenue Foch 29609 Brest FranceJean-Christophe Ianotto, CHU Brest Department of Clinical Hematology, Institute of Cancerology and Hematology Avenue Foch 29609 Brest FranceSylvie Boisramé, CHU Brest Department of Odontology Avenue Foch 29609 Brest FranceGerald Valette, CHU Brest Department of ORL Avenue Foch 29609 Brest FranceChristian Berthou, CHU Brest Department of Clinical Hematology, Institute of Cancerology and Hematology Avenue Foch 29609 Brest France Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Vitamin D deficiency and anemia: a cross-sectional study

Abstract Vitamin D has been suggested to have an effect on erythropoiesis. We sought to evaluate the prevalence of anemia in a population of individuals with vitamin D deficiency compared with those with normal levels in a population of a large integrated healthplan. A cross-sectional analysis in the period 1 January 2004 through 31 December 2006 of subjects with documented concurrent levels of 25-hydroxyvitamin D and hemoglobin were evaluated. Vitamin D deficiency was defined as <30 ng/mL and anemia was defined as a hemoglobin <11 g/dL. A total of 554 subjects were included in the analysis. Anemia was present in 49% of 25-hydroxyvitamin D-deficient subjects compared with 36% with normal 25-hydroxyvitamin D levels (p < 0.01). Odds ratio for anemia in subjects with 25-hydroxyvitamin D deficiency using logistic regressions and controlling for age, gender, and chronic kidney disease was 1.9 (95% CI 1.3–2.7). 25-hydroxyvitamin D-deficient subjects had a lower mean Hb (11.0 vs. 11.7; p = 0.12 ) and a higher prevalence of erythrocyte stimulating agent use (47% vs. 24%; p < 0.05). This study demonstrates an association of vitamin D deficiency and a greater risk of anemia, lower mean hemoglobin, and higher usage of erythrocyte-stimulating agents. Future randomized studies are warranted to examine whether vitamin D directly affects erythropoiesis. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0850-3Authors John J. Sim, Kaiser Permanente Los Angeles Medical Center Division of Nephrology and Hypertension 4700 Sunset Blvd., 2nd Floor Nephrology Los Angeles CA 90027 USAPeter T. Lac, Kaiser Permanente Los Angeles Medical Center Division of Nephrology and Hypertension 4700 Sunset Blvd., 2nd Floor Nephrology Los Angeles CA 90027 USAIn Lu A. Liu, Kaiser Permanente Southern California Department of Research and Evaluation 100 S. Los Robles Av Pasadena CA 91107 USASamuel O. Meguerditchian, Kaiser Permanente Los Angeles Medical Center Division of Nephrology and Hypertension 4700 Sunset Blvd., 2nd Floor Nephrology Los Angeles CA 90027 USAVictoria A. Kumar, Kaiser Permanente Los Angeles Medical Center Division of Nephrology and Hypertension 4700 Sunset Blvd., 2nd Floor Nephrology Los Angeles CA 90027 USADean A. Kujubu, Kaiser Permanente Los Angeles Medical Center Division of Nephrology and Hypertension 4700 Sunset Blvd., 2nd Floor Nephrology Los Angeles CA 90027 USAScott A. Rasgon, Kaiser Permanente Los Angeles Medical Center Division of Nephrology and Hypertension 4700 Sunset Blvd., 2nd Floor Nephrology Los Angeles CA 90027 USA Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Glutathione S-transferase gene deletions and their effect on iron status in HbE/β thalassemia patients

Abstract Iron overload and oxidative stress are main pathophysiological features of HbE/β thalassemia patients. Glutathione S-transferase genes (GSTT1 and GSTM1) are well known detoxification agents, and any mutation in the gene is known to cause oxidative damage. This study was aimed to compare the prevalence of GST deletions in 240 HbE/β thalassemia patients with 100 controls and to determine role of deletions on iron overload. We observed significantly higher frequency of GSTT1 (P = 0.001) and GSTT1/GSTM1 (P = 0.03) in comparison to controls. Patients who had null genotype for both the alleles, i.e., GSTT1/GSTM1 had significantly higher levels of serum iron (P = 0.007) and serum ferritin (P = 0.001) than patients with normal genotype for GST deletions. This is the first study to prove the role of GST gene deletions with iron overload in HbE/β thalassemia. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0847-yAuthors Vineeta Sharma, I.R.C.H. Building (first floor), All India Institute of Medical Sciences (AIIMS) Department of Hematology Ansari Nagar New Delhi 110 029 IndiaBijender Kumar, I.R.C.H. Building (first floor), All India Institute of Medical Sciences (AIIMS) Department of Hematology Ansari Nagar New Delhi 110 029 IndiaRenu Saxena, I.R.C.H. Building (first floor), All India Institute of Medical Sciences (AIIMS) Department of Hematology Ansari Nagar New Delhi 110 029 India Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Subcutaneous anti-d globulin application is a safe treatment option of immune thrombocytopenia in children

Abstract Subcutaneous (sc) administration of anti-d seems to offer the same efficacy as intravenous administration but with less side effects. Here we report our experience with sc anti-d for pediatric immune thrombocytopenia (ITP). A total of 12 children with a median age of 11.2 years had been treated by sc anti-d. They received a median of 2 sc anti-d applications (range 1–31) with a dosage of 250–375 IE/kg body weight. Only in one out of a total of 102 single applications, a minimal and self-limited side effect (chills) had been observed. The mean platelet count was almost doubled after sc anti-d (p < 0.0001). After a median follow-up of 11.4 months, all patients are alive without major bleeding and stay well. We conclude that sc anti-d is not only an efficient means of treating ITP in children but is also a safe and convenient one. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0848-xAuthors Monika M. Trebo, St. Anna Children’s Hospital Division of Hemato-Oncology Kinderspitalgasse 6 1090 Vienna AustriaEva Frey, St. Anna Children’s Hospital Division of Hemato-Oncology Kinderspitalgasse 6 1090 Vienna AustriaHelmut Gadner, St. Anna Children’s Hospital Division of Hemato-Oncology Kinderspitalgasse 6 1090 Vienna AustriaMilen Minkov, St. Anna Children’s Hospital Division of Hemato-Oncology Kinderspitalgasse 6 1090 Vienna Austria Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Idiopathic neutropenia with fewer than 5% dysplasia may be a distinct entity of idiopathic cytopenia of undetermined significance

Idiopathic neutropenia with fewer than 5% dysplasia may be a distinct entity of idiopathic cytopenia of undetermined significance Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0845-0Authors Keiko Ando, Tokyo Medical University The First Department of Internal Medicine (Hematology Division) 6-7-1 Nishishinjuku, Shinjuku-ku Tokyo 160-0023 JapanAtsushi Kodama, Tokyo Medical University Division of Cytogenetics, Central Laboratory Tokyo JapanTamiko Iwabuchi, Tokyo Medical University The First Department of Internal Medicine (Hematology Division) 6-7-1 Nishishinjuku, Shinjuku-ku Tokyo 160-0023 JapanJunko H. Ohyashiki, Tokyo Medical University Intractable Disease Research Center Tokyo JapanKazuma Ohyashiki, Tokyo Medical University The First Department of Internal Medicine (Hematology Division) 6-7-1 Nishishinjuku, Shinjuku-ku Tokyo 160-0023 Japan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Relevance of target cell-induced apoptosis as mechanism of resistance against natural killer cells

Abstract Natural killer (NK) cells contribute to the graft-versus-leukemia effect after allogeneic stem cell transplantation. However, the efficacy of NK cell-mediated tumor cell lysis is limited due to target cell resistance, and target cell-induced apoptosis (TiA) was proposed to contribute to differences in susceptibility to NK cells. Here we analyzed the effects of target cells on the apoptosis of cytokine-activated NK cells in vitro. We found no association of target cell susceptibility and TiA of NK cells in an array of human and murine target-effector cell combinations. Incubation of NK cells with caspase inhibitors blocked TiA incompletely, indicating that TiA is partly based on caspase-independent mechanisms. Modulating NK cell susceptibility against TiA by caspase inhibition did not influence cytotoxic efficacy. Furthermore, we found cytotoxic potential of NK cells to be markedly decreased following first target cell contact. Exhaustion of NK cell activity by first target cell contact was, however, not mediated by TiA. In addition, we found no relevant TiA by lymphoma cell lines against activated murine NK cells. We conclude that TiA represents only a minor factor of target cell resistance against NK cell-mediated cytolysis. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0844-1Authors Justin Hasenkamp, Georg-August-University Goettingen Department of Haematology and Oncology Robert-Koch-Str. 40 37099 Goettingen GermanyAndrea Borgerding, Georg-August-University Goettingen Department of Haematology and Oncology Robert-Koch-Str. 40 37099 Goettingen GermanyGerald Wulf, Georg-August-University Goettingen Department of Haematology and Oncology Robert-Koch-Str. 40 37099 Goettingen GermanyNorbert Schmitz, Asklepios Klinik St. Georg Hamburg Department of Haematology and Stem Cell Transplantation 20099 Hamburg GermanyLorenz Truemper, Georg-August-University Goettingen Department of Haematology and Oncology Robert-Koch-Str. 40 37099 Goettingen GermanyBertram Glass, Asklepios Klinik St. Georg Hamburg Department of Haematology and Stem Cell Transplantation 20099 Hamburg Germany Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Postallogeneic hematopoietic stem cell transplantation relapse of acute myeloid leukemia presenting with salivary gland myelosarcoma

Postallogeneic hematopoietic stem cell transplantation relapse of acute myeloid leukemia presenting with salivary gland myelosarcoma Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0843-2Authors Yu-Hsuan Lai, Kaohsiung Medical University Hospital Division of Hematology-Oncology, Department of Internal Medicine Kaohsiung TaiwanChao-Sung Chang, Kaohsiung Medical University Hospital Division of Hematology-Oncology, Department of Internal Medicine Kaohsiung TaiwanYi-Chang Liu, Kaohsiung Medical University Hospital Division of Hematology-Oncology, Department of Internal Medicine Kaohsiung TaiwanTa-Chih Liu, Kaohsiung Medical University Hospital Division of Hematology-Oncology, Department of Internal Medicine Kaohsiung Taiwan Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Cell cycle and apoptosis regulatory gene expression in the bone marrow of patients with de novo myelodysplastic syndromes (MDS)

Abstract Deregulation of cell cycle and apoptosis pathways are known contributors to the pathogenesis of myelodysplastic syndromes (MDS). However, the underlying mechanisms are not fully clarified. The aim of our study was to examine mRNA expression levels of cell cycle and apoptosis regulatory genes, as well as the percentage of apoptotic and S phase cells and to correlate the findings with clinical characteristics and prognosis. Sixty patients with MDS, classified according to FAB (17 RA, five RARS, 19 RAEB, nine RAEBT, ten CMML) and WHO (ten RA, three RARS, seven RCMD, two RCMD-RS, 11 RAEBI, eight RAEBII, ten CMML, and nine AML) were included in the study. We found increased expression of anti-apoptotic bclxL and mcl1 genes and decreased expression of p21 gene in MDS patients. Moreover, we found increased expression of anti-apoptotic mcl1 gene in patients with higher than Intermediate-1 IPSS group. Multivariate analysis confirmed that combined expression of apoptotic caspases 8, 3, 6, 5, 2, 7, and Granzyme B was decreased in MDS patients. Regarding cell cycle regulatory genes expression, we demonstrated increased expression of cyclin D1 in patients with CMML Increased combined expression of cyclins B, C, D1, and D2 was found in patients with cytogenetic abnormalities. The two pathways seem to be interconnected as shown by the positive correlation between CDKs 1, 2, 4, p21 and the level of apoptosis and positive correlation between apoptotic caspase 3 expression and the percentage of S phase cells. In conclusion, our study showed altered expression of genes involved in apoptosis and cell cycle in MDS and increased expression of cyclin D1 in patients with CMML. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0835-2Authors Christina Economopoulou, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreeceVassiliki Pappa, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreeceSotiris Papageorgiou, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreeceFrieda Kontsioti, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreecePanagiota Economopoulou, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreeceEfstratia Charitidou, National Technical University of Athens School of Applied Mathematical and Physical Sciences Athens GreeceKostas Girkas, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreeceVioletta Kapsimali, Department of Immunology-Histocompatibility, Evangelismos Hospital Athens GreeceChrissoula Papasteriadi, Department of Immunology-Histocompatibility, Evangelismos Hospital Athens GreecePanagiotis Tsirigotis, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreeceEfstathios Papageorgiou, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreeceJohn Dervenoulas, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens GreeceTheofanis Economopoulos, Attikon University Hospital, 2nd Propedeutic Clinic of Internal Medicine 1 Rimini Str., Haidari Athens Greece Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

An extensive analysis of the hereditary hemochromatosis gene HFE and neighboring histone genes: associations with childhood leukemia

Abstract The most common mutation of the HFE gene C282Y has shown a risk association with childhood acute lymphoblastic leukemia (ALL) in Welsh and Scottish case–control studies. This finding has not been replicated outside Britain. Here, we present a thorough analysis of the HFE gene in a panel of HLA homozygous reference cell lines and in the original population sample from South Wales (117 childhood ALL cases and 414 newborn controls). The 21 of 24 variants analyzed were from the HFE gene region extending 52 kb from the histone gene HIST1H1C to HIST1H1T. We identified the single-nucleotide polymorphism (SNP) rs807212 as a tagging SNP for the most common HFE region haplotype, which contains wild-type alleles of all HFE variants examined. This intergenic SNP rs807212 yielded a strong male-specific protective association (per allele OR = 0.38, 95% CI = 0.22–0.64, P (trend) = 0.0002; P = 0.48 in females), which accounted for the original C282Y risk association. In the HapMap project data, rs807212 was in strong linkage disequilibrium with 25 other SNPs spanning 151 kb around HFE. Minor alleles of these 26 SNPs characterized the most common haplotype for the HFE region, which lacked all disease-associated HFE variants. The HapMap data suggested positive selection in this region even in populations where the HFE C282Y mutation is absent. These results have implications for the sex-specific associations observed in this region and suggest the inclusion of rs807212 in future studies of the HFE gene and the extended HLA class I region. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0839-yAuthors Charronne F. Davis, The Institute for Genetic Immunology Genomic Immunoepidemiology Laboratory, HUMIGEN LLC 2439 Kuser Road Hamilton NJ 08690-3303 USAM. Tevfik Dorak, The Institute for Genetic Immunology Genomic Immunoepidemiology Laboratory, HUMIGEN LLC 2439 Kuser Road Hamilton NJ 08690-3303 USA Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Hemophagocytosis associated with leukemia: a striking association with juvenile myelomonocytic leukemia

Abstract The aim of this study was to describe the characteristics and outcome in a group of pediatric patients with hematological malignancies who developed hemophagocytosis at diagnosis or during the disease course. Eight patients with hematological malignancy and associated hemophagocytosis were included. The initial diagnosis was juvenile myelomonocytic leukemia (JMML) in five, nonlymphoblastic leukemia (ANLL) in two, and T-cell lymphoma associated with myeloproliferative syndrome in one patient. Hemophagocytosis was concomitantly present at the time of diagnosis of the primary disease in four of the five patients with JMML and in the two patients with ANLL. Three had abnormalities related to chromosome 8 [(trisomy 8, monosomy 8, and t (8;13) (p11; p12)], and one had inversion 16. Multiple chromosomal losses were present in one patient, including both chromosomes 8 and 16. Bone marrow karyotyping revealed 46, XX; 47, XXX mosaicism in one patient. Two patients had PTPN11 mutation and one patient k-RAS mutation. The patients with JMML and neurofibromatosis (n = 2), the patient with lymphoma and t (8;13) positive AML, and a fourth patient with PTPN11 mutation did not remit and had unfavorable outcomes. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0837-0Authors Sule Unal, Hacettepe University, Faculty of Medicine Department of Pediatrics, Division of Pediatric Hematology 06100 Sıhhiye, Ankara TurkeyMualla Cetin, Hacettepe University, Faculty of Medicine Department of Pediatrics, Division of Pediatric Hematology 06100 Sıhhiye, Ankara TurkeyNuket Yurur Kutlay, University of Ankara, School of Medicine Department of Medical Genetics Ankara TurkeySelin Aytac Elmas, Hacettepe University, Faculty of Medicine Department of Pediatrics, Division of Pediatric Hematology 06100 Sıhhiye, Ankara TurkeyFatma Gumruk, Hacettepe University, Faculty of Medicine Department of Pediatrics, Division of Pediatric Hematology 06100 Sıhhiye, Ankara TurkeyAjlan Tukun, University of Ankara, School of Medicine Department of Medical Genetics Ankara TurkeyMurat Tuncer, Hacettepe University, Faculty of Medicine Department of Pediatrics, Division of Pediatric Hematology 06100 Sıhhiye, Ankara TurkeyAytemiz Gurgey, Hacettepe University, Faculty of Medicine Department of Pediatrics, Division of Pediatric Hematology 06100 Sıhhiye, Ankara Turkey Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Deferasirox (Exjade®) significantly improves cardiac T2* in heavily iron-overloaded patients with β-thalassemia major

Abstract Noninvasive measurement of tissue iron levels can be assessed using T2* magnetic resonance imaging (MRI) to identify and monitor patients with iron overload. This study monitored cardiac siderosis using T2* MRI in a cohort of 19 heavily iron-overloaded patients with β-thalassemia major receiving iron chelation therapy with deferasirox over an 18-month period. Overall, deferasirox therapy significantly improved mean ± standard deviation cardiac T2* from a baseline of 17.2 ± 10.8 to 21.5 ± 12.8 ms (+25.0%; P = 0.02). A concomitant reduction in median serum ferritin from a baseline of 5,497 to 4,235 ng/mL (−23.0%; P = 0.001), and mean liver iron concentration from 24.2 ± 9.0 to 17.6 ± 12.9 mg Fe/g dry weight (−27.1%; P = 0.01) was also seen. Improvements were seen in patients with various degrees of cardiac siderosis, including those patients with a baseline cardiac T2* of <10 ms, indicative of high cardiac iron burden. These findings therefore support previous observations that deferasirox is effective in the removal of myocardial iron with concomitant reduction in total body iron. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0838-zAuthors Anil Pathare, Sultan Qaboos University Hospital Muscat OmanAli Taher, American University Beirut Beirut LebanonShahina Daar, Sultan Qaboos University Muscat Oman Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate

Abstract Prothrombin complex concentrate (PCC) infusion is preferred for emergency reversal of coumarin therapy. Rapid infusion can potentially save crucial time; however, the possible impact of high infusion speed on PCC safety and effectiveness has not been delineated. In a prospective multinational clinical trial with 43 patients receiving PCC (Beriplex® P/N) for emergency reversal of coumarin therapy, infusion speeds were selected by the investigators. In a two-phase statistical analysis, the influence of baseline patient variables and dose on selected infusion speed was assessed. Then, the effect of infusion speed on reduction in international normalized ratio (INR) and on thrombogenicity marker pharmacokinetics was evaluated. Infusion speed ranged widely from 2.0 to 40.0 mL min−1 with a median of 7.5 mL min−1. Selection of infusion speed was not significantly influenced by gender, age, body mass index, presence of acute bleeding, indication for coumarin therapy, baseline INR, or PCC dose. Infusion speed was higher by a median of 2.2 mL min−1 (95% confidence interval, 1.0–4.3 mL min−1) among patients receiving Beriplex P/N volumes ≥80 mL compared with smaller infusion volumes. Infusion speed did not affect INR attained 30 min following PCC infusion. None of the evaluated thrombogenicity marker pharmacokinetic parameters was affected by infusion speed. Infusions in one patient with questionable hemostatic efficacy and another with a possibly PCC-related thromboembolic event were at moderate and slow speeds, respectively. This study provides the first direct evidence that Beriplex® P/N can be rapidly infused for emergency coumarin therapy reversal without altering safety or effectiveness. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0830-7Authors Ingrid Pabinger, Medical University Vienna Department of Internal Medicine, Division of Haematology and Haemostaseology Vienna AustriaAndreas Tiede, Hannover Medical School Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation Hannover GermanyUwe Kalina, Hemophilia/Critical Care, CSL Behring GmbH Clinical Research & Development Marburg GermanySigurd Knaub, Hemophilia/Critical Care, CSL Behring GmbH Clinical Research & Development Marburg GermanyReinhard Germann, Academic Teaching Hospital Feldkirch Department of Anesthesiology and Intensive Care Medicine Feldkirch AustriaHelmut Ostermann, University Hospital Munich—Großhadern, Ludwig Maximilian University Department of Haematology and Oncology, Medical Clinic III Munich Germanyfor the Beriplex® P/N Anticoagulation Reversal Study Group Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Reduction of serum free light chains predict renal recovery

Reduction of serum free light chains predict renal recovery Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-009-0836-1Authors Colin A. Hutchison, University Hospital Birmingham Renal Institute of Birmingham, Department of Nephrology Birmingham B152TH UK Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

Levels of angiogenic factors in patients with multiple myeloma correlate with treatment response

Abstract Angiogenesis plays a significant role in the pathogenesis of multiple myeloma (MM). We have measured concentrations of angiogenesis activators, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and hepatocyte growth factor (HGF), and inhibitors, including endostatin, thrombospondin-1 (TSP-1), and angiostatin in the peripheral and bone marrow blood of MM patients at diagnosis and after high-dose chemotherapy. We have analyzed 96 patients with secretory MM. Serial measurements of angiogenesis factors/inhibitors were analyzed in the plasma by subgroups based on the best treatment response. Concentrations of angiogenic factors were determined in the peripheral blood and bone marrow plasma. There were significant decreases of VEGF and HGF levels and a significant increase in TSP-1 concentrations in the bone marrow plasma of patients who achieved complete or very good partial response in contrast to those who had partial or no response. VEGF and HGF levels decrease but those of TSP-1 increase after successful treatment for MM, indicating a reduction in the rate of angiogenesis. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-009-0834-3Authors Ludek Pour, University Hospital Brno, Masaryk University Departement of Internal Medicine-Hematooncology Brno Czech RepublicHana Svachova, University Research Centre Czech Myeloma Group Brno Czech RepublicZdenek Adam, University Hospital Brno, Masaryk University Departement of Internal Medicine-Hematooncology Brno Czech RepublicMartina Almasi, University Research Centre Czech Myeloma Group Brno Czech RepublicLucie Buresova, Faculty of Science of the Masaryk University Institute of Biostatistics and Analyses at the Faculty of Medicine Brno Czech RepublicTomas Buchler, 1st Faculty of Medicine and Thomayer University Hospital Departement of Oncology Prague Czech RepublicLucie Kovarova, University Research Centre Czech Myeloma Group Brno Czech RepublicPavel Nemec, University Research Centre Czech Myeloma Group Brno Czech RepublicMiroslav Penka, University Hospital Brno, Masaryk University Departement of Internal Medicine-Hematooncology Brno Czech RepublicJiri Vorlicek, University Hospital Brno, Masaryk University Departement of Internal Medicine-Hematooncology Brno Czech RepublicRoman Hajek, University Hospital Brno, Masaryk University Departement of Internal Medicine-Hematooncology Brno Czech Republic Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555

On being metachromatic: Mystique and misunderstanding in mastocytosis

No abstract.

Idiotype-pulsed antigen presenting cells following autologous transplantation for multiple myeloma may be associated with prolonged survival

Vaccines are attractive as consolidation therapy after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We report the results of a phase II trial of the immunotherapeutic, APC8020 (MylovengeTM), given after ASCT for MM. We compared the results with that of other patients with MM who underwent ASCT at Mayo Clinic during the same time period. Twenty-seven patients were enrolled on the trial between July, 1998 and June, 2001, and the outcomes were compared to that of 124 consecutive patients transplanted during the same period, but not enrolled on the trial. The median (range) follow-up for patients still alive from the vaccine trial is 6.5 (2.9-8 years), and 7.1 (6-8 years) in the control group. The median age was 57.4 range (36.1-71.3) in the DB group and 56.4 (range, 30-69) in the trial group. Known prognostic factors including PCLI, B2M, and CRP were comparable between the groups. The median overall survival for the trial patients was 5.3 years (95% CI: 4.0 years - N/A) compared to 3.4 years (95% CI: 2.7-4.6 years) for the DB group (P = 0.02). The median time to progression and progression-free survival for the trial group was similar to the DB group. Although not a controlled trial, the vaccines given after ASCT appear to be associated with improved overall survival compared to historical controls. This approach warrants further investigation to confirm this and define the role of vaccine therapy in myeloma. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc.

Polymorphisms of drug-metabolizing genes and risk of non-Hodgkin lymphoma

Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug-metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non-Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population-based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)AG = 0.67, 95% confidence interval (CI) = 0.55-0.82; ORAG/GG = 0.66, 95% CI = 0.54-0.80) and DLBCL (ORAG = 0.63, 95% CI = 0.49-0.82; ORAG/GG = 0.64, 95% CI = 0.50-0.82). For T-cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (ORAG/GG = 0.65, 95% CI = 0.44-0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (ORAG = 1.28, 95% CI = 1.07-1.54; ORAG/GG = 1.26, 95% CI = 1.06-1.51) and DLBCL (ORAG = 1.32, 95% CI = 1.04-1.66; ORAG/GG = 1.30, 95% CI = 1.03-1.63), but not T-cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc.

Outcome of 93 patients with relapse or progression following allogeneic hematopoietic cell transplantation

Relapse/progression after allogeneic hematopoietic cell transplantation (allo-HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome was overviewed in 292 patients with leukemia/myelodysplastic syndrome who received allo-HCT. Among them, 93 (32%) showed relapse/progression. Cohort 1 was chosen to receive no interventions with curative intent (n = 25). Cohort 2 received reinduction chemotherapy and/or donor lymphocyte infusion (n = 48), and Cohort 3 underwent a second allo-HCT (n = 20). Sixty-three patients received reinduction chemotherapy, and 27 (43%) achieved subsequent complete remission (CR). The incidence of nonrelapse mortality (NRM) was similar among the three cohorts (4, 15, and 5%). The 1-year overall survival (OS) after relapse was significantly better in patients with a second HCT (58%) than in others (14%, Cohorts 1 and 2; P <.001). However, the 2-year OS did not differ between the two groups, which suggests that it is difficult to maintain CR after the second HCT. Multivariate analysis showed that reinduction chemotherapy, CR after intervention, second HCT, and longer time to post-transplant relapse were associated with improved survival. In conclusion, for patients with relapse after allo-HCT, successful reinduction chemotherapy and a second HCT may be effective for prolonging survival without excessive NRM. However, effective measures to prevent disease progression after a second HCT clearly need to be developed. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc.

Reality of complementary and alternative medicine in lymphoma patients: Hope, hype, or help?

No abstract.

Complementary and alternative medicine use among long-term lymphoma survivors: A pilot study

No published survey has specifically addressed the beliefs, knowledge, and usage of complementary and alternative medicine (CAM) in long-term (5-20 years) lymphoma survivors alone. In this pilot project, 95 subjects were randomly selected from a population of 2,475 long-term lymphoma survivors and mailed a questionnaire. The median time from lymphoma diagnosis to completion of the questionnaire was 11 years (range 6-20). Overall, 68% (95% CI: 54-80%) of the long-term lymphoma survivors reported that they have used CAM, a rate higher than the estimated usage rate reported for the general population The most commonly used modalities were chiropractic (39%, 95% CI: 27-53%) and massage therapy (21%, 95% CI: 12-34%). Less than 10% used meditation (5%, 95% CI: 1-15%) and relaxation (7%, 95% CI: 2-17%). In terms of common herbal usage, 5% (95% CI: 1-15%) had used St. John's Wort and 7% (95% CI: 2-17%) had used shark cartilage. Although none of the patients reported that CAM usage was directed specifically towards treating their lymphoma, 4% (95% CI: 0-12%) of patients reported that CAM could cure cancer, and 14% (95% CI: 6-26%) reported that CAM could increase their feeling of control over their health. This pilot study suggests that long-term lymphoma survivors appear to use CAM at a rate higher than the general population. The use of potential agents of risk by the survivors and the lack of access to potentially beneficial modalities highlights the need for further study of CAM in this population. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc.

Estimating platelet production in patients with HIV-related thrombocytopenia using the immature platelet fraction

No abstract.

Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine

Cytoreductive therapy in systemic mastocytosis (SM) includes several drugs whose individual merit has not been well characterized. We retrospectively studied 108 Mayo Clinic patients who met the 2008 WHO diagnostic criteria for SM and received at least one cytoreductive drug. The numbers of patients who were evaluable for response to treatment with interferon-alpha with or without prednisone (IFN-[alpha]), hydroxyurea (HU), imatinib mesylate (IM) or 2-chlorodeoxyadenosine (2-CdA) were 40, 26, 22, and 22, respectively. The corresponding overall (major) response rates, according to recently published consensus criteria, were 53% (18%), 19% (0%), 18% (9%), and 55% (37%). The respective overall response rates in indolent SM, aggressive SM and SM associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD) were 60%, 60%, 45% for IFN-[alpha], 0, 0, 21% for HU, 14%, 50%, 9% for IM and 56%, 50%, 55% for 2-CdA. The absence of mast cell mediator release symptoms in IFN-[alpha]-treated patients and presence of circulating immature myeloid cells in 2-CdA-treated patients predicted inferior response. TET2 mutational status did not influence treatment response. Although the major response rates with these four cytoreductive agents were still suboptimal and HU was mainly used in patients with SM-AHNMD, the current study favors 2-CdA or IFN-[alpha] as first-line current therapy in SM and identifies patients who are likely to respond to such therapy. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc.

Relapsed or refractory nongastric marginal zone B-cell lymphoma: Multicenter retrospective analysis of 92 cases

Over its long survival duration, marginal zone B-cell lymphoma (MZL) routinely involves frequent relapses. In this study, we conducted a retrospective analysis to identify the clinical features and outcomes of relapsed or refractory MZL. From 1995 to 2008, a total of 92 patients with relapsed MZL were retrospectively analyzed. The median age of our subjects was 53.5 years (range: 23-82 years). The most common primary sites of involvement were the orbit and ocular adnexa (28.3%) followed by the lymph node and lymphatic organs (23.9%), and multiple mucosa-associated lymphoid tissue (MALT) sites (13.0%). The median time to relapse from initial diagnosis was 25.5 months. Of the 53 patients with Stage I or II at diagnosis, 42 patients (79.2%) evidenced locoregional recurrence. Among these locoregional relapsed patients, 27 patients achieved CR (54.1%) or PR (18.9%). In addition to the 39 patients initially in advanced Stage III or IV, a total of 50 patients were in advanced stage at relapse. Among those patients with advanced stage at relapse, 44 patients were treated. The overall response rate was 54.5% (24 patients), with 18 CRs and 6 PRs. The median time to progression (TTP) was 34.1 months (95% CI: 11.3-56.9 months) and the estimated 5-year overall survival (OS) was 84.3%. The majority of them was controlled well with salvage treatment, and could achieve prolonged survival. However, patients' refractory to initial therapy and advanced relapse evidenced shorter TTP and OS. Thus, we need to consider more aggressive treatment in cases of refractory MZL or advanced relapsed MZL. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc.

Patients have a "CAM" knowledge gap - But who will fill it?

No abstract.

When yellow jackets attack: Recurrent and severe anaphylactic reactions to insect bites and stings

No abstract.

Bisphosphonates associated osteonecrosis of the jaw: A long-term follow-up of a series of 35 cases observed by GISL and evaluation of its frequency over time

No abstract.

Retrospective comparison of mobilization methods for autologous stem cell transplantation in multiple myeloma

The combination of cyclophosphamide and granulocyte-colony stimulating factor (G-CSF) has widely been used to mobilize hematopoietic stem cells (HSCs) for autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Recently, however, alternative approaches such as G-CSF alone or etoposide followed by G-CSF have been investigated. We, therefore, retrospectively analyzed the effects of these mobilization methods on collection yield and disease outcome in ASCT for MM. We reviewed 146 MM patients from whom we intended to collect stem cells. For mobilization, 67, 58, and 21 patients received cyclophosphamide and G-CSF, etoposide and G-CSF, and G-CSF alone (including nonmyelosuppressive chemotherapy followed by G-CSF), respectively. Among them, 136 achieved the target number of HSCs (at least 2 × 106/kg). Lower creatinine and higher albumin levels at diagnosis were significantly associated with successful yield. A lower number of infused HSCs, use of the etoposide for mobilization and high ISS were associated with delayed hematopoietic recovery. The mobilization methods did not significantly affect either the successful collection of more than 2 × 106 CD34-positive cells/kg or PFS after ASCT. G-CSF alone was sufficient for stem cell mobilization for a single ASCT. The optimal approach to collect HSCs in MM remains to be elucidated. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc.

Identification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells

Follicular lymphoma (FL) frequently transforms into the more aggressive diffuse large B cell lymphoma (DLBCL-tr), but no protein biomarkers have been identified for predictive or early diagnosis. Gene expression analyses have identified genes changing on transformation but have failed to be reproducible in different studies, reflecting the heterogeneity within the tumor tissue and between tumor samples. Gene expression analyses on Affymetrix Human Genome U133 Plus 2.0 arrays were performed, using flow cytometry sorted tumor cells derived from FL and transformed DLBCL. To identify molecular targets associated with the transformation, subsequent immunohistochemistry (IHC) analyses of the corresponding proteins were performed. Using highly purified cells, this study identified 163 genes, which were significantly deregulated during the transformation in a majority of cases. Among the upregulated transcripts, 13 genes were selected for validation using IHC, based on the availability of commercial antibodies, and galectin-3 and NEK2 proteins specifically identify DLBCL-tr, when compared with FL. We demonstrate that by purifying tumor cells through cell sorting, thereby reducing the heterogeneity due to infiltrating cells, it was possible to identify distinct differences between tumor entities rather than variations due to cellular composition. Galectin-3 and NEK2 both identified a subgroup of DLBCL-tr, and the function of these protein markers also suggests a biological role in the transformation process. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc.

Management of hematological malignancies during pregnancy

The management of hematological malignancies during pregnancy is a challenging endeavor, which not only requires technical skills and knowledge by the clinicians but also requires sound clinical judgment and compassion, keeping in mind the patient and family preferences and, ultimately, the wellbeing of the neonate. The incidence of hematological malignancies during pregnancy is rare, ranging from 1 in 1,000 to 1 in 10,000 deliveries, impeding the design and execution of large prospective studies. The purpose of this review is to evaluate the limited existing data and make useful suggestions in the management of acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, plasma cell myeloma, and other hematological malignancies, such as myelodysplastic syndromes and hairy cell leukemia, during pregnancy. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc.

Successful combination treatment of clofarabine, cytarabine, and gemtuzumab-ozogamicin in adult refractory B-acute lymphoblastic leukemia

No abstract.

Erythrocytapheresis in the prevention of recurrent myocardial infarction in sickle cell disease

No abstract.

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

The concept of prodromal chronic myeloproliferative neoplasms has been endorsed by the WHO classification implicating a stepwise evolution of disease. Histology of the bone marrow (BM) and borderline to mildly expressed clinical features play a pivotal role for diagnosing prefibrotic-early primary myelofibrosis. By lowering the platelet count for essential thrombocythemia and regarding BM morphology, early manifestations are tackled. Pre-polycythemic stages of polycythemia vera with a low hemoglobin level at onset are diagnosed by positive JAK2V617F mutation status, a low erythropoietin value, and characteristic BM features. The revised WHO classification incorporates hematological, morphological, and moleculargenetic parameters to generate a consensus-based working diagnosis. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc.

Expression of CD117 by proerythroblasts

No abstract.

Unexpected immune hemolytic anemia in an intensive care ward patient

No abstract.

Recurrent acute thrombocytopenia in the hospitalized patient: Sepsis, DIC, HIT, or antibiotic-induced thrombocytopenia

No abstract.

Crystal-storing histiocytosis in plasma cell myeloma

No abstract.

Cytology of systemic mastocytosis

No abstract.

Help with HELLP

No abstract.

Abnormal hematopoiesis with lysosomal vesicles and giant granules in Chediak-Higashi syndrome

No abstract.

Chronic lymphocytic leukemia cytoplasmic inclusions

No abstract.

Paraneoplastic pemphigus associated with systemic mastocytosis

No abstract.

Splenic hyalohyphomycosis, molecularly and immunologically consistent with invasive aspergillosis, in a patient with acute lymphoblastic leukemia

No abstract.

Hydroxycarbamide-induced dermopathy

No abstract.

Near total effacement of bone marrow by medulloblastoma

No abstract.

CLINICAL PROFILE AND HOME MANAGEMENT OF SICKLE CELL-RELATED PAIN: The Enugu (Nigeria) Experience

THE BENEFIT OF ATG IN IMMUNOSUPPRESSIVE THERAPY OF CHILDREN WITH MODERATE APLASTIC ANEMIA

RHABDOMYOSARCOMA OF THE EXTREMITIES: A Focus on Tumors Arising in the Hand and Foot

INCIDENCE OF PRIMARY CENTRAL NERVOUS SYSTEM TUMORS AMONG CHILDREN IN BELGRADE (SERBIA), 1991-2004

PANEL REACTIVE ANTIBODY IN THALASSEMIC SERUM INHIBITS PROLIFERATION AND DIFFERENTIATION OF CORD BLOOD CD34 + CELLS IN VITRO

ALLOGENEIC STEM CELL TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROMES IN CHILDREN: A Report from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON)

SEVERE HYPOCHROMIC MICROCYTIC ANEMIA IN A PATIENT WITH CONGENITAL ATRANSFERRINEMIA

EFFECT OF SOMATOSTATIN ANALOGUE OCTREOTIDE IN MEDULLOBLASTOMA IN XENOGRAFT AND CELL CULTURE STUDY

SUCCESSFUL TREATMENT OF KASABACH-MERRITT SYNDROME WITH VINCRISTINE AND DIAGNOSIS OF THE HEMANGIOMA USING THREE-DIMENSIONAL IMAGING

A NOVEL L218P MUTATION IN NADH-CYTOCHROME B5 REDUCTASE ASSOCIATED WITH TYPE I RECESSIVE CONGENITAL METHEMOGLOBINEMIA

PLASMA HEPARANASE AS A SIGNIFICANT MARKER OF TREATMENT RESPONSE IN CHILDREN WITH HODGKIN LYMPHOMA: Pilot Study

ALLOGENEIC CORD BLOOD TRANSPLANTATION IN CHILDREN WITH HEMATOLOGICAL MALIGNANCIES: A Long-Term Follow-Up Single-Center Study

EXTRA-OSSEOUS EWING SARCOMA

BONE MARROW TRANSPLANTATION OR HYDROXYUREA FOR SICKLE CELL ANEMIA: Long-Term Effects on Semen Variables and Hormone Profiles

ANTIBODY TITRATION AND IMMUNE RESPONSE OF IRANIAN β-THALASSEMIC PATIENTS TO HEPATITIS B VIRUSE VACCINE (BOOSTER EFFECT)

GROWTH STATUS IN CHILDREN AND ADOLESCENTS WITH SICKLE CELL DISEASE

CD10 AND CD34 EXPRESSION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN MOROCCO: Clinical Relevance and Outcome

HEPATITIS G VIRUS INFECTION IN MULTITRANSFUSED EGYPTIAN CHILDREN

TRENDS IN SURVIVAL AFTER CHILDHOOD CANCER IN SLOVENIA BETWEEN 1957 AND 2007

SPERM CRYOPRESERVATION PRACTICES AMONG ADOLESCENT CANCER PATIENTS AT RISK FOR INFERTILITY

SPONTANEOUS THROMBOSIS OF HEPATIC ANEURYSMS IN AN INFANT WITH WISKOTT-ALDRICH SYNDROME

MULTIPLE CHROMOSOME ABNORMALITIES IN THE PLEURAL FLUID OF A PATIENT WITH RECURRENT EWING SARCOMA

THROMBOLYTICS FOR HYPERACUTE STROKE IN CHILDREN

HEMORHEOLOGICAL PARAMETERS IN CHILDREN WITH IRON-DEFICIENCY ANEMIA AND THE ALTERATIONS IN THESE PARAMETERS IN RESPONSE TO IRON REPLACEMENT

HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILD HEMATOLOGIC MALIGNANCIES WITH G-CSF-MOBILIZED MARROW GRAFTS WITHOUT T-CELL DEPLETION: A Single-Center Report of 45 Cases

HYPEREOSINOPHILIC SYNDROME IN CHILDHOOD: Clinical and Molecular Features of Two Cases

THE CASE OF A 1-YEAR-OLD GIRL WITH HEREDITARY HYPERFERRITINEMIA CATARACT SYNDROME

ANAPLASTIC LARGE CELL LYMPHOMA WITH PRIMARY INVOLVEMENT OF SKELETAL MUSCLE: A Rare Case Report and Review of the Literature

POLAND SYNDROME WITH INTRACRANIAL GERM CELL TUMOR IN A CHILD

RHABDOMYOLYSIS DUE TO Escherichia coli SEPSIS IN THREE PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

PARVOVIRUS B19-INDUCED PERSISTENT PURE RED CELL APLASIA IN A CHILD WITH T-CELL IMMUNODEFICIENCY

ALTERED IRON METABOLISM IN CHILDREN WITH HUMAN IMMUNODEFICIENCY VIRUS DISEASE

ACUTE LYMPHOBLASTIC LEUKEMIA SECONDARY TO CHEMORADIOTHERAPY FOR PERIVASCULAR EPITHELIOID CELL TUMOR OF UTERUS

CHOOSING THERAPY FOR ADOLESCENT FEMALES WITH CANCER: Fertility Should Matter

RELAPSE OF PRIMITIVE MEDIASTINAL LYMPHOMA AS A MYELOID MASS FOLLOWING BEAM AUTOLOGOUS TRANSPLANT AND SUBSEQUENT REFRACTORINESS TO MATCHED UNRELATED UMBILICAL CORD BLOOD ALLOGRAFT

TRANSFORMATION OF MYELODYSPLASTIC SYNDROME TO T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN A YOUNG ADULT

DIFFERENTIAL microRNA EXPRESSION IN CHILDHOOD B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA

UNDULANT COURSE OF AFP: A Sign of Tumor Activation or Not?

IS THE TREATMENT FOR CHILDHOOD SOLID TUMORS ASSOCIATED WITH LOWER BONE MASS THAN THAT FOR LEUKEMIA AND HODGKIN DISEASE?

EXPRESSION OF PTEN AND SHP1, INVESTIGATED FROM TISSUE MICROARRAYS IN PEDIATRIC ACUTE LYMPHOBLASTIC, LEUKEMIA

COEXISTENCE OF SYMPTOMATIC IRON-DEFICIENCY ANEMIA AND DUODENAL NODULAR LYMPHOID HYPERPLASIA DUE TO GIARDIASIS: Case Report

BONE FRACTURE: An Unusual Presentation of Acute Megakaryoblastic Leukemia

INVASIVE ASPERGILLOSIS OF THE SMALL BOWEL IN AN INFANT WITH ACUTE MYELOID LEUKEMIA AND INTESTINAL OBSTRUCTION

EXCESSIVE NAKED MEGAKARYOCYTE NUCLEI IN MYELODYSPLASTIC SYNDROME MIMICKING IDIOPATHIC THROMBOCYTOPENIC PURPURA: A Complicated Pre- and Post-transplantation Course

LATE EFFECTS OF TREATMENT FOR WILMS TUMOR

HOMOZYGOUS α-THALASSEMIA WITH TRISOMY 7 MOSAICISM IN A LIVE-BORN INFANT

THYROID CANCER IN LEBANESE CHILDREN AND ADOLESCENTS: A 15-Year Experience at a Single Institution

CERVICAL LYMPHADENOPATHY IN CHILDHOOD EPIDEMIOLOGY AND MANAGEMENT

HEMOPHAGOCYTOSIS: The Cause of Anemia and Thrombocytopenia in Congenital Syphilis

ASSOCIATION BETWEEN GENETIC POLYMORPHISM IN DNA REPAIR GENES AND RISK OF B-CELL LYMPHOMA