Prospective evaluation of the effect of deferasirox on hematologic response in transfusion-dependent patients with low-risk MDS and iron overload.

OBJECTIVES: To assess the reduction of transfusions rate in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) with iron overload treated with deferasirox. METHODS: Prospective observational study. Primary endpoint was reduction in transfusion requirements (RTR) at 3 months, (assessed on 8-week period). Secondary endpoints were hematologic improvement according to International Working Group (IWG) 2006 criteria at 3, 6, and 12 months. RESULTS: Fifty-seven patients were evaluable. After 3 months of chelation, no effect was seen on transfusion requirement (5.9 packed red blood cells (PRBC) vs 5.8 before chelation). According to the Kaplan-Meier analysis, the probability of RTR at 3, 6, and 12 months was assessed as 3.5%, 9.1%, and 18.7%, respectively. Median duration of RTR was 182 days. However, during the 12-month follow-up after deferasirox initiation, 17 patients (31.5%) achieved minor erythroid response [HI-E] according to IWG criteria, 10 of whom having achieved Hb improvement at month 12. CONCLUSION: After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused patients with low-risk MDS. However, deferasirox could induce 31% of erythroid response during the 12-month follow-up period thus suggesting that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a subset of patients with MDS and iron overload.

From the observation of atypical cells on blood smear to the diagnosis of mast cell leukemia: a case report in a 79 year old woman consulting for anemia.

Mast cell leukemia is an extremely rare disease, which belongs to the systemic mastocytosis group (WHO 2016). We are reporting the case of a 79-year-old woman, without any hematological particular history consulting for hyperthermia, repeated malaise and subacute anemia. Her clinical examination was normal. Unusual cells were seen on blood and bone marrow smears. They represent more than 10% of blood nucleated cells end more than 20% of the bone marrow nucleated cells. Bone marrow immunophenotyping was performed to characterize these cells. It revealed a cell subset expressing the surface antigens CD117, CD2 and CD25. This immunophenotypic profile is the hallmark of malignant mast cells. Then mast cell leukemia diagnosis could have been made and KIT gene sequencing highlighted the N822Y mutation in exon 17. The patient was initially treated with midostaurin, a tyrosine kinase inhibitor. Lack of therapeutic response and absence of the KIT D816V mutation led to switch to imatinib, following the latest scientific recommendations.

[WHIM syndrome: presumptive diagnosis based on myelokathexis on bone marrow smear]. / Diagnostic de syndrome WHIM évoqué devant l'observation de myélokathexis.

The WHIM syndrome is a rare congenital immunodeficiency disorder characterized by human papillomavirus (HPV)-induced warts, hypogammaglobulinemia, bacterial infections and myelokathexis. Myelokathexis refers to abnormal retention of mature neutrophils in the bone marrow leading to severe neutropenia. We report the case of a 20 year old man presenting with chronic and severe neutropenia since early childhood without established diagnosis. He was addressed for chronic parodontal disease treatment. Examination of bone marrow smear showed morphological abnormalities of mature neutrophils strongly suggestive of myelokathexis. Diagnosis of WHIM syndrome was confirmed by molecular analysis: a nonsense mutation was identified in the gene encoding CXCR4, the CXCL12 (or SDF-1) chemokine receptor which notably controls cell adhesion to the marrow stroma and thereby regulates mature leukocytes release from the bone marrow. Treatment of the disease usually consists in prophylactic anti-infective measures including intravenous immunoglobulins administration, oral antibiotic prophylaxis and more recently HPV vaccination. Long term G-CSF therapy did not show any significant efficiency in preventing recurrent infections. The use of specific CXCR4 antagonist is being currently evaluated.