Search

Supplementary Table 6 from FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis

Supplementary Table 2 from FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis

Supplementary Table 3 from FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis

Supplementary Figure 1 from FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis

Supplementary Table 1 from FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis

Supplementary Table 5 from FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis

Supplementary Methods, Table Legends 1-6 from FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis

Supplementary Table 4 from FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis

International audience; In order to improve the outcome observed with azacitidine (AZA) in higher-risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA-PLUS was a phase II trial that, in a "pick a winner" approach, randomly assigned patients with higher-risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six\,cycles, 69 (21.4%) CR\,+\,PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7\,months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six\,cycles were higher in the AZA-LEN And AZA-IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy-related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our "pick a winner" randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.

Resume Au travers de sa commission d’ethique, l’Institut national de la transfusion sanguine a interroge les differentes strates des relations interpersonnelles qui se nouent tout au long de la chaine transfusionnelle. Au travers de parcours tres divers, les professionnels autour de la transfusion ont des approches a la fois divergents sur des specificites de metier et aussi des points de vue convergents autour de valeurs partagees. La chaine transfusionnelle rend possible la relation entre (ai) les personnes malades ou blessees, requerant ce type de soin ; (ai) les donneurs de sang sans lesquels l’objet meme de cette offre de soin n’existerait pas ; et (aiii) un arsenal de professionnels prenant en charge tous les aspects techniques, logistiques, medicaux et administratifs de la transfusion. Cette categorie professionnelle est plurielle : au plus proche des donneurs, au plus proche des personnes malades, au plus proche du produit sanguin detache du donneur mais pas encore administre a la personne malade, ou au plus pres de l’Etat regulateur et administrateur. Ces professionnels sont soumis a differents niveaux de tensions dans le cadre de leur(s) mission(s), dans une relation aussi dependante de leur passe ou leur absence de passe relatif aux periodes sombres de la transfusion. Dans ce contexte, l’ethique apparait comme le point de convergence et le sujet pour lequel nul debatteur n’est plus — ou moins — legitime qu’un autre. Cette journee s’est deroulee en trois temps principaux : (bi) un debat sur le don et l’accueil du candidat au don ou du donneur de sang ; (bii) un debat sur le transfert du don a la personne malade (au beneficiaire) au risque de la dette ; (biii) une synthese et l’identification de pistes de travail. Le present compte-rendu, loin d’en faire un verbatim, en est davantage le recueil des points saillants.

Treatment with azacitidine (AZA) has been suggested to be of benefit for higher-risk myelodysplastic syndrome (HR-MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR-MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time-varying variable in multivariable analysis. A Cox Regression model with time-interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non-CK) and International Prognostic Scoring System risk (high versus intermediate-2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P

PURPOSE: While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy. METHODS AND MATERIALS: Patients with untreated supradiaphragmatic HL without risk factors (age ≥ 50 years, 4 to 5 nodal areas involved, mediastinum-thoracic ratio ≥ 0.35, and erythrocyte sedimentation rate ≥ 50 mm in first hour without B symptoms or erythrocyte sedimentation rate ≥ 30 mm in first hour with B symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20 Gy in 10 fractions), or standard-dose involved-field RT (36 Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36 Gy (n=239), 20 Gy of involved-field RT (n=209), or no RT (n=130). RESULTS: Randomization to the no-RT arm was prematurely stopped (≥20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] -1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P

Background In France, advance directives are favourably perceived by most of the population, although the drafting rate is low. This ambivalence is challenging because advance directives are meant to promote the autonomy and freedom of choice of patients. The purpose of this study was to analyse the content of advance directives written by patients suffering from malignant haemopathies to better understand how patients put them into practice. These could be relevant as early as the initial diagnosis of haematological malignancies because of the uncertain course of the disease. Methods This was a multicentre, qualitative, descriptive study. The advance directives written by patients with malignant haemopathies treated in one of the six French hospital departments were included in the study from 01/06/2008 to 15/04/2016. A thematic analysis of the advance directives was performed by two researchers: a senior haematologist and a research assistant. Results The median age of the patients was 69. Most were women (sex ratio: 0.59), living as a couple (57%), with lymphoid pathologies (66%), who were still alive two years after the instructions were written (63%) and had nominated a health care proxy (88.6%). Free texts (62.9%) were richer in content than pre-defined forms. The advance directives were used in three ways: for a purely legal purpose, to focus on medical treatments or actions, or to communicate a message to the family. Three main themes emerged: (1) refusal of medical treatment (100%), in which patients express refusal of life-sustaining care (97.1%). The actual treatments or the moment when they should be limited or stopped were not always mentioned in detail. (2) A desire for effective pain relief to avoid suffering (57.1%) and (3) messages for their family (34.3%), such as funeral arrangements (17.1%) and messages of love or trust (14.3%). Conclusions Patients who write advance directives are not necessarily at the end of their lives. Their content mainly conveys treatment wishes, although patients also use them to pass on personal messages to their close family. This emerging role of advance directives to communicate messages within the family should be valued, even if it is not their original purpose.

Objectives Geriatric patients with hematologic malignancies (HMs) are prescribed targeted and supportive care treatments that add to the preexisting polypharmacy (PP). PP is associated with an increased risk of potentially inappropriate medications (PIM) and drug-drug interactions (DDI) resulting in increased hospitalization and mortality in the elderly. As very few data exist on these medication issues in the context of HMs, the objective of this study was to evaluate prevalence of PP, DDI and PIM use at baseline and 3 months among elderly patients with HMs who received baseline geriatric assessment. Methods PP, DDI and PIM use were assessed by a clinical pharmacist at two time points in patients over 75 years with HMs undergoing chemotherapy. PP was defined as the concurrent use of five or more medications. DDIs were evaluated according to the literature and prescription analysis software. PIMs were assessed according to the Laroche list. Results 122 patients (mean age 81.5; 6.6 medications) were included and after 3 months, 86 patients (5.8 medications) were available for a second assessment. Prevalence of PP, PIM and DDI at inclusion was 75.4%, 34.4% and 71.3%, respectively. PP was the only medication risk that was significantly reduced (p Conclusion This observational study highlighted that PP decreased over time but neither DDI nor PIM use were reduced. A pharmacist-led evaluation might help to manage these medication issues.

Resume Dans nos societes occidentales le renforcement de la valeur d’autonomie a pris corps a travers differentes dispositions legislatives, dont la possibilite de rediger des directives anticipees. Leur mise en œuvre questionne les professionnels de sante. Objectif L'objectif principal de ce travail etait de recueillir la perception pluridisciplinaire de soignants, puis, secondairement, de decrire leur pratique d’information et d’aide a la redaction des directives anticipees. Methode Cette enquete est a visee prospective. Un questionnaire a ete remis un jour donne a la promotion 2016/2017 d’un diplome inter-universitaire en soins palliatifs (DIUSP). Le questionnaire se composait de dix questions fermees, 12 questions ouvertes et un encadre libre. Resultats Le sentiment des professionnels de sante etait heterogene, 56,3 % se disaient a l’aise, 44 % d’avis partage. Plusieurs moments sont cites pour presenter les directives anticipees. Sur la forme, 25 % des repondants pensaient qu’allier un modele type avec des zones de texte libre permet d’engager un dialogue patient soignant. Les psychologues consideraient que les directives anticipees ne doivent servir qu’a transmettre des informations medicales. Si la plupart des repondants ont delivre des informations sur les directives anticipees, 81,3 % n’ont jamais accompagne de patient pour leur redaction et 57,1 % n’ont pas eu a les utiliser. Leur valeur opposable est adequate pour 56,3 % des repondants. Conclusion La perception des directives anticipees est favorable, mais leur appropriation par des professionnels de sante sensibilises a la demarche palliative reste delicate. Des difficultes ressortent telles qu’aborder le sujet de la fin de vie, trouver le temps necessaire pour echanger avec les personnes qui souhaitent en rediger.

BACKGROUND: Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas.METHODS: ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m2 and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152.FINDINGS: Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2-not evaluable) in the A+CHP group and 20·8 months (12·7-47·6) in the CHOP group (hazard ratio 0·71 [95% CI 0·54-0·93], p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group.INTERPRETATION: Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile.FUNDING: Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.

Resume Le recueil du consentement eclaire n’est pas restreint a l’inclusion des personnes malades dans un protocole de recherche clinique. La recherche de ce consentement doit s’appliquer a tous les soins courants particulierement quand la procedure therapeutique est a risque eleve. Les principes ethiques qui doivent accompagner la methodologie de recueil de ces consentements eclaires sont rappeles avec une proposition de recommandations de bonnes pratiques dans la relation medecin malade. Une homogeneisation du contenu des consentements eclaires d’un centre greffeur a l’autre est indispensable pour lutter contre les inegalites dans le recueil du consentement des donneurs et des receveurs. Cependant, il est fortement recommande d’adapter son contenu par un veritable dialogue medecin malade/donneur. Dans une demarche qui vise a uniformiser les procedures d’allogreffe de cellules souches hematopoietiques, la Societe francophone de greffe de moelle et de therapie cellulaire (SFGM-TC) a organise les sixiemes ateliers d’harmonisation des pratiques en allogreffe en septembre 2015 a Lille. Le but de ces ateliers annuels est de trouver un terrain d’entente entre des centres qui le souhaitent dans les domaines ou la litterature ne fournit pas de reponses incontestables et consensuelles. L’objectif de cet article en annexe aux travaux des Ateliers de Lille est de rappeler l’etat des lieux de la legislation francaise et les droits des patients concernant leurs consentements aux soins.

BackgroundIf the law called “Leonetti” enacted in 2005 allows patients to prepare and submit their advance directives (AD), its ownership in hospital services is still very punctual, even in clinical hematology services where illnesses are severe and can be life-threatening. The objective of our study was to evaluate the impact of a dual approach: caregiver training and information to patients on AD. The secondary objectives are to analyze the obstacles to their appropriation by caregivers and better understanding of the meaning patients give to the AD.

Resume L’histoire de Vincent Lambert est devenue « l’affaire Lambert ». Un protocole de limitation therapeutique, engage pour ce patient en etat vegetatif depuis 6 ans, a fait l’objet d’une mediatisation importante suite a un conflit soignant et une partie de la famille, entrainant une succession de decisions de justice, dont certaines sont actuellement en cours d’instruction. L’interpretation du principe de collegialite qui a ete faite dans cette affaire interpelle les professionnels de sante, les juristes et le grand public. Une collaboration recente entre le service d’hematologie clinique et de therapie cellulaire du CHU de Limoges et la faculte de droit (Observatoire des mutations institutionnelles et juridiques [OMIJ]), sur un axe de recherche centre sur le consentement du patient, a conduit a une reflexion commune sur cette affaire. Nous presentons ici notre questionnement ethique et le regard croise de medecins et de juristes. Que penser de la lecture faite du principe de collegialite glissant vers une obligation d’unanimite d’une famille elargie ? Comment les equipes soignantes doivent-elles proceder lorsqu’elles prennent en charge un patient hors d’etat de s’exprimer, qui n’a pas laisse de directives ecrites, quand elles estiment que la poursuite du traitement traduit une obstination deraisonnable ? Comment respecter la volonte du patient inconscient exprimee anterieurement par oral ? En l’absence de personne de confiance, qui est legitime au sein de la famille a etre le porte-parole du patient ? L’immixtion du droit dans la relation de soin et du juge dans cette decision medicale est-elle pertinente ?

Intravascular hemolysis in Paroxysmal nocturnal hemoglobinuria (PNH) can effectively be controlled with eculizumab, a humanized monoclonal antibody that binds complement protein C5. We report here a retrospective comparison study between 123 patients treated with eculizumab in the recent period (>2005) and 191 historical controls (from the French registry). Overall survival (OS) at 6 years was 92% (95%CI, 87 to 98) in the eculizumab cohort versus 80% (95%CI 70 to 91) in historical controls diagnosed after 1985 (HR 0.38 [0.15 to 0.94], P = 0.037). There were significantly fewer thrombotic events (TEs) in the group of patients treated with eculizumab (4% [1-10]) as compared to the historical cohort (27% [20-34]). However, we found that TEs may still occur after the initiation of eculizumab treatment and that previous TEs still have a negative impact on survival. Evolutions to myelodysplastic syndrome or acute leukemia were similar in both cohorts. There was less evolution to aplastic anemia in the treatment group. In multivariate analysis, absence of a previous TE and treatment with eculizumab were associated with a better OS. Treatment with eculizumab improves overall survival in classic PNH patients without increasing the risk of clonal evolution.

Les traitements medicamenteux contre les cancers et les hemopathies malignes ont fortement evolue ces dernieres annees, du fait d’un accroissement de la diversite pharmacologique des molecules disponibles, avec notamment une explosion des formes sous-cutanees ou orales. Ces nouvelles galeniques sont a l’origine d’une modification profonde du parcours de soin du patient, au profit du maintien a domicile. Le rapport de la Haute Autorite de sante (HAS), publie debut 2015, soulignait la valeur ajoutee pour les patients fragiles, et notamment les enfants, les personnes âgees et les patients en phase avancee, de l’administration des traitements au domicile, en particulier lorsque leur administration est courte (perfusion courte ou administration sous-cutanee). Alors que les industriels pharmaceutiques proposent un nombre croissant d’adaptations galeniques aux therapeutiques innovantes, privilegiant les formes orales ou sous-cutanees, c’est un veritable challenge auquel doit s’adapter l’ensemble des professionnels de sante, notamment hospitaliers, pour se coordonner et se reorganiser afin de securiser prescription, administration, et surveillance de ces nouvelles molecules delivrees en dehors de leur lieu d’exercice. Il s’agit moins, aujourd’hui, de choisir entre hopital et domicile, que d’organiser une gradation des possibilites de prise en charge, rendant possible l’administration des traitements a domicile lorsque les conditions de qualite des soins le permettent. L’hematologie est consideree par la HAS comme le secteur prioritaire ou la chimiotherapie a domicile devrait se developper. Ainsi, que ce soit le souci de la qualite de vie des patients fragilises par la maladie, ou les possibilites recemment ouvertes par les nouvelles molecules et leurs formes galeniques facilitant l’administration, les conditions semblent reunies pour faire evoluer la repartition de l’administration des chimiotherapies entre l’hopital et le domicile. Suite a la publication du rapport de la HAS, cet article se propose de faire le point sur les enjeux que representent ces traitements a domicile pour l’hematologie, les contraintes qu’ils generent et les amenagements necessaires dans la tarification pour lui permettre d’evoluer, en particulier dans le contexte du developpement des formes sous-cutanees.

Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes. ispartof: Oncotarget vol:7 issue:19 pages:27255-27266 ispartof: location:United States status: published

« Si j’avais pu prevoir, j’aurais… », « Si j’avais ete informe, je n’aurais pas… », « Si on m’avait predit que…, je n’aurais jamais cru que… », « Si l’on m’avait prevenu que… »C’est par ces paroles de personnes atteintes d’hemopathies malignes, entendues lors de reunions associatives, que la necessite est apparue, comme une evidence, de reflechir et de se questionner au sein de la commission d’ethique de la SFH, sur l’accompagnement [...]

Resume Un des principaux changements de paradigmes introduits par les lois sur les droits des malades depuis 2002 est la primaute du principe d’autonomie de la personne, et de facon consecutive, la recherche d’un consentement aux soins. L’information loyale, claire, comprehensible est indispensable mais seulement si elle est appropriee a la situation. Ces notions precisent une relation entre la personne malade et l’equipe des soignants mais elle laisse pour autant des zones d’incertitude quant a la completude de l’information delivree et relative a la capacite de la personne autonome a recevoir l’entierete ou la partialite de l’information et a l’assimiler ? A quoi consent-on en effet quand on est pris en soin ? Quels effets secondaires annoncer (et recevoir) afin que l’acceptation d’un soin soit encore une option ? N’est-ce pas plutot a qui consent-on de donner sa confiance dans un plan de soin ? Appliques a la transfusion (don de sang et de cellules souches, reception de produits sanguins), tels sont les sujets et les questions qui ont ete debattus lors du seminaire annuel de l’Institut national de la transfusion sanguine en decembre 2018. Les debats, nourris, n’ont pas clos la question, mais permis l’emergence de points meritant certainement une poursuite et un approfondissement de la reflexion.

International audience; No abstract available

Background - Reports of patients with secondary acute promyelocytic leukemia (APL) have increased in recent years, particularly for those who received treatment with mitoxantrone, and retrospective studies have suggested that their characteristics and outcomes were similar to those of patients with de novo APL. Methods - The authors investigated patients with de novo and secondary APL who were included in the ongoing APL-2006 trial. Patients with secondary APL who were included in that trial also were compared with a previous retrospective cohort of patients with secondary APL. Results - In the APL-2006 trial, 42 of 280 patients (15%) had secondary APL. Compared with the retrospective cohort, patients with secondary APL in the APL-2006 trial had a lower incidence of prior breast carcinoma (35.7% vs 57%; P = .03) and a higher incidence of prior prostate carcinoma (26.2% vs 4.7%; P Conclusions - Although the incidence of secondary APL appears to be stable over time, evolving strategies for the treatment of primary cancers have reduced its occurrence among breast cancer patients but have increased its incidence among patients with prostate cancer. The current results confirm prospectively that patients with secondary APL have characteristics and outcomes similar to those of patients with de novo APL.

Summary The present study describes the current clinical practice and hospital management of adults with immune thrombocytopenia (ITP) between 2009 and 2012 in France, based on the national discharge hospital database. Adult ITP patients were managed almost exclusively in public hospitals. A relatively stable number of patients, around 3200 per year, were hospitalized for ITP annually over the 4-year period, about two-thirds of whom were newly-diagnosed ITP. Re-hospitalizations tended to decrease over the study period. Intravenous immunoglobulin administration, concerning half of ITP hospitalized patients, and rituximab administration were stable over time, whereas a slight decrease of splenectomies was observed.

Les syndromes myelodysplasiques (SMD) sont des affections clonales des cellules souches pluripotentes, caracterisees par une hematopoiese inefficace, responsable de cytopenies sanguines qui contrastent avec une moelle generalement riche. De plus, les SMD evoluent frequemment en leucemie aigue myeloide (LAM) et constituent les plus frequents des etats preleucemiques de l’adulte.Les SMD predominent chez le sujet âge, avec une mediane d’âge au diagnostic de l’ordre de 70 [...]

Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively ( P = .05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively ( P = .21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.

International audience; B-cell chronic lymphocytic leukemia (B-CLL) cells are resistant to apoptosis, and consequently accumulate to the detriment of normal B cells and patient immunity. Because current therapies fail to eradicate these apoptosis-resistant cells, it is essential to identify alternative survival pathways as novel targets for anticancer therapies. Overexpression of cell-surface G protein-coupled receptors drives cell transformation, and thus plays a critical role in malignancies. In this study, we identified neurotensin receptor 2 (NTSR2) as an essential driver of apoptosis resistance in B-CLL. NTSR2 was highly expressed in B-CLL cells, whereas expression of its natural ligand, neurotensin (NTS), was minimal in both B-CLL cells and patient plasma. Surprisingly, NTSR2 remained in a constitutively active phosphorylated state, caused not by a mutation-induced gain-of-function but rather by an interaction with the oncogenic tyrosine kinase receptor TrkB. Functional and biochemical characterization revealed that the NTSR2-TrkB interaction acts as a conditional oncogenic driver requiring the TrkB ligand brain-derived neurotrophic factor (BDNF), which unlike NTS is highly expressed in B-CLL cells. Together, NTSR2, TrkB and BDNF induce autocrine and/or paracrine survival pathways that are independent of mutation status and indolent or progressive disease course. The NTSR2-TrkB interaction activates survival signaling pathways, including the Src and AKT kinase pathways, as well as expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL. When NTSR2 was downregulated, TrkB failed to protect B-CLL cells from a drastic decrease in viability via typical apoptotic cell death, reflected by DNA fragmentation and Annexin V presentation. Together, our findings demonstrate that the NTSR2-TrkB interaction plays a crucial role in B-CLL cell survival, suggesting that inhibition of NTSR2 represents a promising targeted strategy for treating B-CLL malignancy.

Autologous stem-cell transplantation (autoSCT) is considered a standard treatment of non-frail patients with mantle cell lymphoma (MCL), but little is known about outcome of MCL patients relapsing after autoSCT. We therefore sought to analyse the outcome after autoSCT failure and the efficacy of a rescue stem-cell transplantation (SCT) in this setting. Patients with MCL were eligible if they had relapsed after autoSCT performed between 2000 and 2009. A total of 1054 patients could be identified in the EBMT registry. By contacting the transplant centres, a full dataset could be retrieved for 360 patients. Median overall survival (OS) after relapse of the whole study group was 19 months. A long (> 12 months) interval between autoSCT and relapse [P < 0.001, hazard ratio (HR) 0.62], primary refractory disease (P < 0.02, HR 1.92), prior high-dose ARA-C treatment (P = 0.04, HR 1.43), and the year of relapse (P = 0.02, HR 0.92) significantly influenced OS from relapse in multivariate analysis. Eighty patients (22%) received a rescue allogeneic SCT (alloSCT). Relapse incidence, non-relapse mortality, and OS 2 years after alloSCT was 33% [confidence interval (95% CI 21% to 45%)], 30% (95% CI 19% to 42%), and 46% (95% CI 33% to 59%), respectively. Remission duration after autoSCT was the only variable significantly affecting the outcome of salvage alloSCT. In contrast, rescue autoSCT was not associated with long-term disease control. However, individual patients survived long term even without salvage transplantation. MCL recurrence within 1 year after autoSCT has an extremely dismal outcome, while the prognosis of patients with longer remission durations after autoSCT is significantly better. AlloSCT may offer the possibility of durable survival when performed for patients with a remission duration of more than 12 months after first autoSCT, but the favourable effect of a salvage alloSCT in this setting needs further validation.

Les recommandations de la Societe de Reanimation en Langue Francaise (SRLF) [1], publiees en 2002, concernant les limitations et arrets de therapeutiques actives en reanimation adulte, sont a ce jour une initiative unique qui a modifie les pratiques professionnelles des services de reanimation. Dans un contexte different, de nombreuses situations posent au quotidien, dans les services d’hematologie, le probleme de la proportionnalite des soins et d’une eventuelle obstination deraisonnable, encore appelee communement acharnement therapeutique. En hematologie comme dans d’autres disciplines, cette conduite therapeutique peut etre cause de souffrance chez les malades, leurs familles et les soignants eux-memes, et souleve de graves problemes ethiques. C’est pourquoi le premier objectif du groupe Ethique de la Societe Francaise d’Hematologie (SFH), cree par son conseil d’administration en fevrier 2004, a ete de proposer a la discipline une reflexion et des recommandations. Ce texte a ete redige en s’inspirant du texte de la SRLF [1], des reflexions et de l’experience des membres du groupe et des donnees de la litterature. Il sera presente aux membres du conseil d’administration de la SFH et diffuse au sein de la discipline « hematologie ». Ce projet est apparu particulierement necessaire avec l’apparition de nouveaux textes legislatifs (en particulier la loi du 4 mars 2002), l’avis n° 60 du Comite Consultatif National d’Ethique du 27 janvier 2000 intitule « Fin de vie, arret de vie, euthanasie », la publication des recommandations de la Conference de consensus de l’ANAES des 14 et 15 janvier 2004 sur l’Accompagnement des patients en fin de vie et de leurs proches et la proposition de loi n° 1882 du 30 novembre 2004 relative aux droits des malades et a la fin de vie. Ce texte est propose comme une incitation a la reflexion plutot que comme une serie de recommandations qui s’ajouteraient aux textes officiels actuels ou en cours d’elaboration.