Mise au point d'une thrombopénie

Thrombocytopenia is defined by a platelet level below 150 G/l. However, the limit of 100 G/l seems more appropriate to determine which thrombocytopenia will require further investigation. Initially, a thorough medical history should be performed as well as screening for any signs of bleeding. After having excluded the presence of platelet aggregates, it should be determined whether thrombocytopenia is isolated or associated with other abnormalities (cytopenias coagulation disorder, abnormal renal or liver tests). Causes of thrombocytopenia along with the biological tests to achieve diagnosis, will be detailed in this article. We will then determine the medical emergencies that will need to be addressed to a reference center: active bleeding biological signs of disseminated intravascular coagulation, acute renal failure, platelet count < 30 G/l (or < 50 G/l if the patient is on anticoagulation or antiplatelet therapy) significant and/or brutal onset pancytopenia. Outside these situations where vital prognosis is engaged, the patient should be rapidly addressed in case of platelet count between 30 and 50 G/l without any concomitant anticoagulation or antiplatelet therapy. Platelet levels between 50 and 100 G/l will require investigation, without any urgency, in outpatient haematology clinic.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

DIAGNOSIS AND TREATMENT OF PERIPHERAL T-CELL LYMPHOMAS: UPDATE RECOMMENDATIONS OF THE BELGIAN HEMATOLOGY SOCIETY (BHS)

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive diseases associated with poor outcomes. Recent progress in understanding of the biology and pathogenesis based on molecular profiling and next-generation sequencing has led to the introduction of new provisional entities in the World Health Organization (WHO) classification system of 2017 and to the emergence of new drugs.1 Previous Belgian guidelines were published in 2013.2 This review will discuss the diagnosis, work-up and treatment of PTCL including these advances as well as the limitation of the availability of drugs according to the Belgian reimbursement rules

Predictive factors of response and survival among chronic myelomonocytic leukemia patients treated with azacitidine

Treatment of CMML remains a clinical challenge, with no drug demonstrating clear clinical benefit. Even if azacitidine is approved in the treatment of CMML, its role remains disputed. We report a cohort of 76 CMML patients (according to WHO classification) treated with azacitidine in 3 programs (French AZA compassionate program, Cleveland Clinic Foundation and H. Lee Moffitt Cancer Center). 45% had CMML2, and 55% had splenomegaly and/or WBC counts >13G/L, which are known to be poor prognostic factors in CMML. All patients received AZA for at least one cycle, and the median number of cycles administered was 6. Thirty-three patients (43%) achieved a response according to IWG 2006 criteria, including 13 complete remissions (17%). Median survival was 29 months. Increased bone marrow blast percentage and proliferative features of the disease, including splenomegaly and high WBC counts, were significantly associated with shorter survival. By multivariate analysis, only marrow blasts >10% and palpable splenomegaly had prognostic impact on survival. Although promising, the efficacy of azacitidine in advanced CMML needs to be confirmed in a randomized prospective study

Prognostic Factors of Response and Survival in CMML Patients Treated with Azacitidine (AZA)

Abstract Abstract 1726 Background: Treatment of CMML remains a clinical challenge, with no drug demonstrating clear clinical benefit. AZA yielded a survival benefit in higher risk MDS in a study that included few patients with CMML (AZA 001 trial, Lancet Oncol, 2009). Several small series of CMML treated by Decitabine (Wijermans, Leuk Res. 2008, Aribi A, Cancer. 2007 and Kantarjian H, Blood. 2007) and AZA (Scott, Br J Haematol. 2010) have been reported, but numbers were small with heterogeneous risk factors. Methods: A cohort of CMML pts (according to WHO classification) treated with AZA in 3 programs (French AZA compassionate program, Cleveland Clinic Foundation and H. Lee Moffitt Cancer Center) were reviewed. All pts received AZA for at least one cycle (75 mg/m2/d during 7 days every 28 d). Response was evaluated according to IWG 2006 criteria in patients with WBC 13G/l), in agreement with our previous experience (Wattel, Blood 1996; Braun, Blood 2011 online). Results: Between 2004 and 2009, 79 CMML pts received AZA. The median age was 70 y (range 33–85), M/F: 50/29. Median interval from diagnosis to treatment was 12 months in 34 pts. At onset of AZA, median WBC, Hb level and platelet count were 11.4 G/l (range 7–122), 10 g/dl (range 6.3–15.2) and 59 G/l (range 9–1214), respectively. According to the WHO classification, 53% were CMML1 and 47% CMML2. Forty six percent of pts had WBC > 13 G/l and 32% had palpable SM (44% pts had neither of those features, 32% pts had one and 23% had both). Among pts with WBC<13G/l, IPSS was low or int 1 in 24% pts and high or int 2 in 30%. Prior to AZA, 48% pts received previous therapy, including growth factors in 13%, hydroxyurea in 18% and intensive chemotherapy in 17% patients. Karyotype was normal (57%), with chromosome 5/7 abn (14%), and with other cytogenetic changes (29%). The median number of cycles of AZA administered was 6 (range 1–40). Thirty-four pts (43%) responded including CR (16%), PR (1.5%), marrow CR (8%), hematological improvement (HI) (18%). Among 60 pts who received more than 4 cycles, 33 (55%) responded, including 13 (22%) who achieved CR. Patients who achieved response were significantly older (median 71 vs 66 years in non responders, p=0.0170).WBC count (p=0.4241), WBC >13 G/L (p=0.483), Hb level (p= 0.4529), platelet count (p= 0.1658), marrow blast % (p=0.4278), palpable SM (p= 0.319), cytogenetics (p=0.947), disease duration (p= 0.808), prior therapy (p= 0.277) and prior therapy excluding GF (p= 0.147) had no impact on response. Twenty-six patients progressed to AML after a median of 630 d (range 85–1165 d), including 12/34 of the responders (6 CR, 1 PR and 5 HI). The median overall survival (OS) from initiation of AZA (OS) was 654 d. In univariate analysis, prior therapy when ESA were excluded (p=0.0488), palpable SM (median 420 d vs 870 d, p= 0.0230), WBC>13 G/l (420 vs 775, p= 0.0412), presence of palpable SM and/ or WBC>13G/l (none: median 876d vs either: 750d vs both: 401d, p= 0.0054) (figure 1) IPSS in pts with WBC10 % (383d vs 682d, p=0.028) significantly influenced OS while Karyotype (p=0.4217), sex (p= 0.5174) and Hb level had no influence on OS. By multivariate analysis, only marrow blasts>10 % (HR=2.19 (1.13–4.2), p=0.02) and presence of proliferative features (WBC>13G/L and/or palpable SM) (HR= 2.08 (.94 −4.6),p= 0.06) had prognostic value for OS. Finally, using a landmark analysis performed at 3 mo, Patients who achieved a response had a significantly better OS compared to patients who failed to respond (median 889 d vs 569 d, p= 0.047). Conclusion: In this population of CMML patients with generally poor prognostic features, the response rates (ORR 43%) and overall survival (21 mo) with AZA treatment was similar to that previously reported in higher risk MDS. No significant predictive factors for response to AZA were identified, but marrow blast % and proliferative features (including increased WBC count and/or splenomegaly) were adverse prognostic factors for survival. Disclosures: Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Celgene: Membership on an entity's Board of Directors or advisory committees. List:Celegene: Consultancy. Fenaux:Celgene: Membership on an entity's Board of Directors or advisory committees. Komrokji:Celgene: Research Funding, Speakers Bureau