Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation w

A case with a cytogenetically cryptic variant of the inv(16)(p13q22)/t(16;16)(p13;q22)

publisher: Elsevier articletitle: A case with a cytogenetically cryptic variant of the inv(16)(p13q22)/t(16;16)(p13;q22) journaltitle: Cancer Genetics articlelink: http://dx.doi.org/10.1016/j.cancergen.2014.04.009 content_type: simple-article copyright: Copyright © 2014 Elsevier Inc. All rights reserved.status: publishe

Clonal chromosomal abnormalities in Ph-negative cells in chronic myeloid leukemia: an unusual case evolving to secondary acute myeloid leukemia

publisher: Elsevier articletitle: Clonal chromosomal abnormalities in Ph-negative cells in chronic myeloid leukemia: an unusual case evolving to secondary acute myeloid leukemia journaltitle: Cancer Genetics articlelink: http://dx.doi.org/10.1016/j.cancergen.2014.10.007 content_type: simple-article copyright: Copyright © 2015 Elsevier Inc. All rights reserved.status: publishe

Treatment of Peripheral T-cell Lymphomas: recommendations of the Belgian Hematological Society

info:eu-repo/semantics/publishe

Analysis of phenotype and outcome in essential thrombocythemia with CALR or JAK2 mutations.

The JAK2 V617F mutation, the thrombopoietin receptor MPL W515K/L mutation and calreticulin (CALR) mutations are mutually exclusive in essential thrombocythemia and support a novel molecular categorization of essential thrombocythemia. CALR mutations account for approximately 30% of cases of essential thrombocythemia. In a retrospective study, we examined the frequency of MPL and CALR mutations in JAK2 V617F-negative cases of essential thrombocythemia (n=103). In addition, we compared the clinical phenotype and outcome of CALR mutant cases of essential thrombocythemia with a cohort of JAK2 V617F-positive essential thrombocythemia (n=57). CALR-positive cases represented 63.7% of double-negative cases of essential thrombocythemia, and most carried CALR type 1 or type 2 indels. However, we also identified one patient who was positive for both the JAK2 V617F and the CALR mutations. This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, leukocyte counts, hemoglobin, and hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F-positive essential thrombocythemia. Analysis of the CALR mutant group according to indel type showed that CALR type 1 deletion is strongly associated with male gender. CALR mutant patients had a better overall survival than JAK2 V617F-positive patients, in particular patients of age 60 years or younger. In conclusion, this study in a Belgian cohort of patients supports and extends the growing body of evidence that CALR mutant cases of essential thrombocythemia are phenotypically distinct from JAK2 V617F-positive cases, with regards to clinical and hematologic presentation as well as overall survival

Analysis of Phenotype and Outcome in Essential Thrombocythemia with CALR or JAK2 mutations

The JAK2 V617F mutation, the thrombopoietin receptor MPL W515K/L mutation and the Calreticulin (CALR) mutations are mutually exclusive in essential thrombocythemia and support a novel molecular categorization of essential thrombocythemia. CALR mutations account for approximately 30 % of essential thrombocythemia cases. In a retrospective study, we have examined the frequency of MPL and CALR mutations in JAK2 V617F negative essential thrombocythemia (n=103). In addition, we compared the clinical phenotype and outcome of CALR mutant essential thrombocythemia with a cohort of JAK2 V617F positive essential thrombocythemia (n=57). CALR positive cases represented 63.7% of double negative essential thrombocythemia, and most carried CALR Type 1 or Type 2 indels. However, we also identified one patient, who was positive for both the JAK2 V617F and the CALR mutations. This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, lower leukocyte counts, hemoglobin, hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F positive essential thrombocythemia. Analysis of the CALR mutant group according to indel type showed that CALR Type 1 deletion is strongly associated with male gender. CALR mutant patients had a better overall survival than JAK2 V617F positive patients, in particular patients of age 60 years or younger. In conclusion, this study on a Belgian cohort supports and extends the growing body of evidence that CALR mutant is phenotypically distinct from JAK2 V617F positive essential thrombocythemia, with regard to its clinical and hematological presentation as well as the overall survival.status: publishe

The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study.

This retrospective multicenter study in patients with chronic myeloid leukemia in chronic phase was undertaken to confirm the clinical relevance of imatinib plasma concentrations monitoring in daily practice. Forty-one patients, with 47 imatinib plasma measurements, were analyzed during treatment with imatinib given at a fixed 400mg daily dose. A significant inverse relationship of imatinib concentration with the patients' weight was observed (Pearson's test: p=0.02, R(2)=0.1). More interestingly, patients with poor response (switched to another tyrosine kinase inhibitor because of imatinib failure, or because of disease progression after an initial response) displayed a significantly lower mean imatinib concentration as compared to patients maintained on imatinib (822ng/mL vs 1099ng/mL; Student's t-test, p=0.04). Failure or disease progression occurred more often in patients in the lowest quartile of imatinib concentrations compared to patients in the highest quartile (p=0.02, logrank test). No correlation could be established with other biological or clinical parameter, including complete cytogenic response and major molecular response. IN CONCLUSION: in patients treated with imatinib at a fixed daily dose of 400mg, imatinib plasma concentrations decreased with increasing body weight and were lower in patients switched to another tyrosine kinase inhibitor due to imatinib failure. Systematic determination of imatinib plasma trough levels should be encouraged in such patients

Use of chimerism analysis after allogeneic stem cell transplantation : Belgian guidelines and review of the current literature

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option in both adult and pediatric patients with malignant and non-malignant hematological diseases. Chimerism analysis, which determines the donor or recipient origin of hematopoietic cells in HSCT recipients, is an essential aspect of post-HSCT follow-up.Objectives: To review the current literature and develop Belgian consensus guidelines for the use of chimerism analysis in the standard of care after allogeneic HSCT.Methods: Non-systematic review of the literature in consultancy with the members of the BHS transplantation committee.Results: Clinical application with regards to prediction of graft failure or relapse as well as cell source are reviewed. A consensus guideline on the use of chimerism analysis after HSCT is presented.Conclusion: Monitoring of the dynamics or kinetics of a patient's chimerism status by serial analysis at fixed time points, as well as on suspicion of relapse or graft failure, is needed to monitor engraftment levels, as well as disease control and possible relapse