Saint-Paul-de-Vence, France


Saint-Paul-de-Vence, France
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PubMed | Lyon University Hospital Center, Nancy University Hospital Center, Caen University Hospital Center, Hematologie and 4 more.
Type: | Journal: European journal of haematology | Year: 2016

This study investigates whether achieving complete remission (CR) with undetectable minimal residual disease (MRD) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL) affects outcome.We retrospectively studied 46 patients transplanted for CLL and evaluated for post-transplant MRD by flow cytometry.At transplant time, 43% of the patients were in CR, including one with undetectable MRD, 46% were in partial response and 11% had refractory disease. After transplant, 61% of the patients achieved CR with undetectable MRD status. By multivariate analysis, reaching CR with undetectable MRD 12 months after transplant was the only factor associated with better progression-free survival (PFS) (p=0.02) and attaining undetectable MRD, independently of the time of negativity, was the only factor that correlated with better overall survival (OS) (p=0.04).Thus achieving undetectable MRD status after allo-SCT for CLL is a major goal to improve post-transplant outcome. This article is protected by copyright. All rights reserved.

PubMed | CHRU, Lyon University Hospital Center, Institut Universitaire de France, Caen University Hospital Center and 6 more.
Type: Clinical Trial, Phase I | Journal: American journal of hematology | Year: 2015

Lenalidomide is manageable and effective in multiple myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25 mg/day for 21/28 days, the highest possible dose, in Waldenstrms Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. RV-WM-0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for 1 year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Seventeen RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow-up of 36 months, median TTP was 16 months (95% CI 5.5-26), the 5-year OS was 91%. The most frequent adverse eventsgrade 3 at 15 mg were 14% anemia and 43% neutropenia. The MTD of lenalidomide is 15 mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing.

PubMed | Groupe Hospitalier Of Linstitut Catholique Of Lille, Institute Paoli Calmettes, Center Henri Becquerel, Caen University Hospital Center and 9 more.
Type: Journal Article | Journal: American journal of hematology | Year: 2015

Acquired -thalassemia myelodysplastic syndrome (MDS) (ATMDS) is an acquired syndrome characterized by a somatic point mutation or splicing defect in the ATRX gene in patients with myeloid disorders, primarily MDS. In a large MDS patient series, the incidence of ATMDS was below 0.5%. But no large series has yet assessed the incidence of ATMDS in microcytic MDS. In this study, we focused on patients with MDS and unexplained microcytosis, which was defined as absence of iron deficiency, inflammatory disease, or history of inherited hemoglobinopathy. Our data confirm the low frequency of ATRX mutations in MDS: 0% in an unselected clinical trial cohort of 80 low risk MDS, 0.2-0.8% in a multicenter registry of 2,980 MDS and 43% of MDS with unexplained microcytosis in this same registry. In addition, we reported four novel mutations of the ATRX gene in ATMDS. This study further determines the frequency of ATRX mutations and highlights the importance of microcytosis to detect ATRX mutations within MDS patients.

PubMed | University of Nantes, Medical University of Graz, Hospital Of Sant Pau, CHU Hematology and 18 more.
Type: Journal Article | Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation | Year: 2014

To determine whether umbilical cord blood transplantation (UCBT) is an alternative cure for myelofibrosis (MF), we evaluated 35 UCBTs reported to Eurocord. Seven patients had secondary acute myeloid leukemia (AML) at UCBT, and median age at UCBT was 54 years. Twenty-four patients received a reduced-intensity conditioning (RIC) regimen, and 17 of 35 patients received total body irradiation (2 to 12 Gy)-fludarabine-cyclophosphamide (TCF) conditioning. The median follow-up was 24 months. The cumulative incidence of neutrophil recovery at 60 days was 80%. Fifteen patients relapsed after UCBT. The 2-year overall survival and event-free-survival (EFS) rates were 44% and 30%, respectively. All patients given TCF achieved neutrophil and platelet recovery, and the use of TCF was associated with superior EFS in the RIC population (44% versus 0%, P = .001). Patients with transformation to AML had similar outcomes to patients with less advanced stages. In conclusion, despite graft failure remaining a major concern, the role of UCBT in the management of MF, especially using RIC TCF-based regimens, deserves further investigation to improve results.

PubMed | Lyon University Hospital Center, Hematologie adulte, Angers University Hospital Center, Reims University Hospital Center and 12 more.
Type: Journal Article | Journal: Leukemia | Year: 2015

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only a curative treatment in patients with higher risk myelodysplastic syndrome (MDS), although demethylating agents (DMA) have been reported to improve survival. The advantage of HSCT over other treatment comes from retrospective studies and the aim of the current study was to prospectively test this hypothesis, analyzing in particular patients from the pre-transplant period to avoid the selection bias of performing transplantation. This study was conducted to compare overall survival in MDS patients candidates to transplantation according to donor availability. The majority of patients (76%) received a treatment with DMA after registration, 69% had a human leukocyte antigen (HLA)-identical donor, 70% of whom were transplanted. Baseline patient and disease characteristics were similar according to donor availability. Four-year overall survival was significantly better in patients with an HLA matched donor (37%) compared to patients without donor (15%). There was also evidence that this overall survival advantage was because of transplantation. Mortality risk was decreased after transplantation but it became significant only after the second year post transplant, because of early transplant-related mortality. Our results appear to justify, in higher risk MDS, a transplantation approach in all potential candidates who have an HLA identical donor.

Locasciulli A.,Ematologia Pediatrica e Trapianto di Midollo | Bacigalupo A.,II Divisione Ematologia e Trapianto di Midollo | Bruno B.,II Divisione Ematologia e Trapianto di Midollo | Montante B.,Ematologia Pediatrica e Trapianto di Midollo | And 4 more authors.
British Journal of Haematology | Year: 2010

In order to assess the epidemiology of Hepatitis-Associated Aplasia (HAA) and compare treatment outcome of HAA with non-HAA patients, we evaluated 3916 aplastic anaemia patients reported to the European Registry between 1990 and 2007. Year, month, season of diagnosis, type and outcome of first-line therapy were analysed. Prevalence of HAA (n = 214) in Europe was 5%. Compared to non-HAA patients, HAA patients were younger (15 vs. 20 years, P < 0·001), with a male prevalence (68% vs. 58%P = 0·002), and were treated earlier after diagnosis (46 vs. 62 d; P < 0·001). No significant differences were found regarding the year or month of diagnosis. No geographic clusters could be identified. Actuarial survival at 10 years after first-line immunosuppression was 69%, and did not differ according to aetiology. The 10-year actuarial survival after transplantation was 70%, and was comparable in HAA and non-HAA patients, when stratified for age and donor type. In a multivariate Cox analysis, increasing age and delayed treatment were significant negative indicators for survival. In conclusion, the incidence of HAA was 5% and was evenly distributed over time and geographic areas in Europe. Treatment outcome and predictive variables, were comparable in patients with or without HAA. © 2010 Blackwell Publishing Ltd.

PubMed | DBIM, Hematologie, Service des maladies du sang, Service dHematologie and 3 more.
Type: Journal Article | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

Accurate quantification of monoclonal IgM immunoglobulins is essential for response assessment in patients with Waldenstrms macroglobulinaemia (WM). The propensity of IgM to form multimers in serum makes sample evaluation by current laboratory methods particularly challenging.We assessed the precision and linearity of IgM and IgM heavy/light chain (HLC, Hevylite) assays, and established reference intervals using 120 normal donor sera. We compared the quantitative performance of HLC assays with serum protein electrophoresis (SPE) and total IgM nephelometry for 78 diagnostic samples and follow-up samples from 25 patients with WM. Comparisons were made between the three methods for diagnostic sensitivity and response assessment.IgM and IgM HLC assays showed low imprecision and good linearity. There was good agreement between summated HLC (IgM + IgM) and total IgM (measured nephelometrically; RNephelometric assessment of IgM and IgM HLC pairs offers a quantitative alternative to traditional laboratory techniques for the measurement of monoclonal IgM and may aid in the management of WM. Clin Cancer Res; 22(20); 5152-8. 2016 AACR.

PubMed | CHR Metals Limited, Brest University Hospital Center, Besancon University Hospital Center, Nancy University Hospital Center and 11 more.
Type: Clinical Study | Journal: American journal of hematology | Year: 2015

Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4).

PubMed | Hematologie, Lyon University Hospital Center, Medecine interne, Nancy University Hospital Center and 5 more.
Type: Journal Article | Journal: La Revue de medecine interne | Year: 2015

Once characterized by a very poor outcome, multiple myeloma (MM) now has a significantly prolonged survival, with major improvements allowed by the use of novel agents: proteasome inhibitors (first-in-class bortezomib) and immunomodulatory compounds (IMiDs; first-in-class thalidomide and lenalidomide). However, the vast majority -if not all- of patients with MM ultimately end up being refractory to all existing drugs, including these efficient novel agents. There is a clear unmet medical need in this situation, which warrants the development of the next generation of proteasome inhibitors and IMiDs, as well as new drug classes. This review focuses on pomalidomide, the next generation IMiD, recently approved by the US FDA and the EMA for patients with relapsed or refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy.

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