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We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti‐thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14‐0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35‐0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.

Monosomy 7 [-7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with -7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with -7). Patients with del(7q) or -7 had similar demographic and disease-related characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in -7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequency between the two groups. Patients harbouring =2 mutations had a worse outcome than patients with

For cancers lacking standard treatments, comparing new agents with existing treatments is problematic. Here we discuss the study design from the AZA-001 trial, which compared azacitidine with 3 frequently used conventional care regimens (CCR) for higher-risk myelodysplastic syndromes. Before randomization, physicians preselected the most appropriate of 3 CCR for each patient, after thorough examination. Patients were then randomized to azacitidine or CCR. Patients randomized to CCR received their preselected treatment, thus including patients otherwise excluded as poor candidates for a single comparator. This design may serve as a template in other cancers lacking standard therapy. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved

Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens.In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m(2) per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French-American-British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799.Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21.1 months (IQR 15.1-26.9), median overall survival was 24.5 months (9.9-not reached) for the azacitidine group versus 15.0 months (5.6-24.1) for the conventional care group (hazard ratio 0.58; 95% CI 0.43-0.77; stratified log-rank p=0.0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50.8% (95% CI 42.1-58.8) of patients in the azacitidine group were alive compared with 26.2% (18.7-34.3) in the conventional care group (p0.0001). Peripheral cytopenias were the most common grade 3-4 adverse events for all treatments.Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care.

Contains fulltext : 79862schattenberg.pdf (Publisher’s version ) (Closed access) Matched unrelated donor stem cell transplantation (MUD-SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD-SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced-intensity conditioning (RIC, n = 87) or conventional myeloablative (CONV, n = 44) MUD-SCT between 2000 and 2005 were included. Median time from diagnosis to MUD-SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft: 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD-SCT and had failed a previous autograft more frequently than CONV recipients. Non-relapse mortality (NRM) was 24% and 30% at 100-d and 1-year, respectively. After a median follow-up of 36 months, 17% of the patients developed disease progression, the 3-year progression-free survival (PFS) being 47%. Three-year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUD-SCT results, even in heavily pre-treated populations, in a meaningful PFS and OS.