Management of Myelodysplastic Syndrome Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the French Society of Bone Marrow Transplantation and Cell Therapies

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P ¼ .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P ¼.007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT

Evolution du taux de gammaglobulines chez les patients atteints de leucémie lymphoïde chronique traités par ibrutinib

# 11-12International audienc

Longitudinal copy number, whole exome and targeted deep sequencing of 'good risk' IGHV-mutated CLL patients with progressive disease

Disease progression in IGHV-M CLL with 'good-risk' cytogenetics is frequently associated with co-evolution of 'poor risk' driver mutations and DNA methylation changes.Drug resistance in IGHV-M CLL may be consequent upon the emergence of an IGHV-U cloneThe biological features of IGHV-M CLL responsible for disease progression are still poorly understood. We undertook a longitudinal study close to diagnosis, pre-treatment and post relapse in thirteen patients presenting with cMBL or Stage A disease and good risk biomarkers (IGHV-M genes, no del(17p) or del(11q) and low CD38 expression) who nevertheless developed progressive disease, of whom ten have required therapy. Using cytogenetics, FISH, genome-wide DNA methylation and copy number analysis together with whole exome, targeted deep- and Sanger sequencing, at diagnosis we identified mutations in established CLL driver genes in nine (69%), non-coding mutations (PAX5 enhancer region) in three, and genomic complexity in two patients. Branching evolutionary trajectories predominated (n=9/13), revealing intra-tumoural epi- and genetic heterogeneity and sub-clonal competition prior to therapy. Of the patients subsequently requiring treatment, two had sub-clonal TP53 mutations that would not be detected by standard methodologies, three qualified for the very-low risk category defined by integrated mutational and cytogenetic analysis and yet had established or putative driver mutations and one patient developed progressive, therapy-refractory disease associated with the emergence of an IGHV-U clone. These data suggest that extended genomic and immunogenetic screening may have clinical utility in patients with apparent good risk disease.Leukemia accepted article preview online, 05 February 2016. doi:10.1038/leu.2016.10

Facteurs pronostiques clinico-biologiques et génomiques de la survie dans le syndrome de Richter

International audienc

Proteomic analysis of proteins responsive to drought and low temperature stress in a hard red spring wheat cultivar

Drought stress is becoming more prevalent with global warming, and has been shown to have large effects on gluten proteins linked to wheat bread making quality. Likewise, low temperature stress can detrimentally affect proteins in wheat. This study was done to determine the differential expression of high molecular weight (HMW) gluten proteins in a drought and low temperature stressed high quality hard red spring wheat cultivar (PAN3478), against a control. The three treatments were applied in the greenhouse when the main tillers of each pot were at the soft dough stage, on 15 pots per replication, three replications and three plants per pot for each treatment. Seed of main tillers were bulked and randomly sampled. Removal of gliadins was done with 50% (v/v) 1-propanol. The HMW proteins were then extracted and separated by 2-dimensional gel electrophoresis. Gels were analyzed with SameSpots Progenesis (version 4.6.1.218). The protein spots that had p values lower than 0.05 and fold value equal to or greater than 1.2 were considered significantly differentially expressed. Spots were excised from the gel, digested with trypsin and analysed by mass spectrometry. The proteins were identified by matching the spectra to theoretical data from the Swissprot protein database. There was a 1.3 to 1.8 fold change in 19 protein spots due to the cold treatment. The drought treatment caused 1.3 to 3.8 fold change in 20 spots that were significantly differentially expressed. Two spots, one with matching peptide sequences to HMW glutenin proteins DX5, DY10 and PC256, and one to HMW glutenin protein PW212, were differentially expressed under both drought and cold stress. Other proteins differentially expressed under cold stress included proteins with similar peptides to alpha/beta-gliadin A-IV, fructan 1- exohydrolase w3, a number of HMW-GS P212 and HMW-GS DY12 proteins and HMW-GS DY10, chloroplastic Nad(P)H-quinone oxidoreductase subunit 2 A, alpha/beta-gliadin and low molecular weight-GS PTDUCD1. Under drought stress ATPase, HMW-GS PW212, HMW/GS (HMW subunit 12) and DY10, Ubiquitin and Eukaryotic translation initiation factor isoform 4G-2 were differentially expressed. The HMW glutenins are known to have a large effect on baking quality, and clearly protein spots with similar peptide sequences with especially HMW-GS DY12, PW212, PC256, HMWGS DX5 and DY10 were responsive to cold and drought stress, and could directly influence baking quality

J Clin Oncol

PURPOSE: Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. PATIENTS AND METHODS: Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. RESULTS: From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% ( P = .01). The proportional hazards assumption was rejected for OS ( P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively ( P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm ( P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm ( P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm ( P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm ( P = .04), and fewer patients required a second treatment after ICL. CONCLUSION: Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML

Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia.

International audienc

L’ajout de la lomustine bénéficie aux leucémies myéloïdes aiguës du sujet âgé avec cytogénétique non-défavorable et d’un profil moléculaire à haut risque de l’European Leukemia Net 2017

# 07-03International audienc