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The optimum management approach for patients with relapsed or refractory follicular lymphoma remains uncertain. Autologous stem cell transplantation (autoSCT) is considered a standard option in suitable, younger patients with relapsed follicular lymphoma. AutoSCT is associated with very durable remissions in a minority of subjects, but also with significant, well-established toxicities. Although positron emission tomography (PET) status prior to autoSCT is an established prognostic factor in diffuse large B-cell lymphoma and Hodgkin lymphoma, no data exist in follicular lymphoma. We describe survival outcomes according to pre-transplant PET status, classified by the Lugano criteria into complete metabolic remission (CMR) versus non-CMR, in 172 patients with relapsed or refractory follicular lymphoma within a national, multicenter, retrospective British Society of Blood and Marrow Transplantation and Cellular Therapy registry study. The median number of lines of therapy prior to SCT was three (range, 1-6). The median follow-up after SCT was 27 months (range, 3-70). The median progression-free survival for all patients after autoSCT was 28 months (interquartile range, 23- 36). There was no interaction between age at transplantation, sex, number of months since last relapse, Karnofsky performance status or comorbidity index and achieving CMR prior to autoSCT. Superior progression-free survival was observed in 115 (67%) patients obtaining CMR versus 57 (33%) non-CMR patients (3-year progression-free survival 50% vs. 22%, P=0.011) and by pre-SCT Deauville score (continuous variable 1-5, hazard ratio [HR]=1.32, P=0.049). PET status was independently associated with progression-free status (non-CMR HR=2.02, P=0.003), overall survival (non-CMR HR=3.08, P=0.010) and risk of relapse (non-CMR HR=1.64, P=0.046) after autoSCT by multivariable analysis. Our data suggest that pre- SCT PET status is of clear prognostic value and may help to improve the selection of patients for autoSCT.

Prognostic stratification is critical for making therapeutic decisions and maximizing survival of patients with acute myeloid leukemia. Advances in the genomics of acute myeloid leukemia have identified several recurrent gene mutations whose prognostic impact is being deciphered. We used HaloPlex target enrichment and Illumina-based next generation sequencing to study 24 recurrently mutated genes in 42 samples of acute myeloid leukemia with a normal karyotype. Read depth varied between and within genes for the same sample, but was predictable and highly consistent across samples. Consequently, we were able to detect copy number changes, such as an interstitial deletion of BCOR, three MLL partial tandem duplications, and a novel KRAS amplification. With regards to coding mutations, we identified likely oncogenic variants in 41 of 42 samples. NPM1 mutations were the most frequent, followed by FLT3, DNMT3A and TET2. NPM1 and FLT3 indels were reported with good efficiency. We also showed that DNMT3A mutations can persist post-chemotherapy and in 2 cases studied at diagnosis and relapse, we were able to delineate the dynamics of tumor evolution and give insights into order of acquisition of variants. HaloPlex is a quick and reliable target enrichment method that can aid diagnosis and prognostic stratification of acute myeloid leukemia patients., (Copyright© Ferrata Storti Foundation.)

Background: Long-term outcome after hematopoietic stem cell transplantation including late transplant-related events is of increasing interest. The aim of this study was to evaluate the incidence of cardiovascular events after allogeneic HSCT and to search for their risk factors., Design and Methods: This is a retrospective multicenter European Group of Blood and Marrow Transplantation (EBMT) analysis, including 548 long-term survivors treated in ten EBMT transplant centers, who underwent hematopoietic stem cell transplantation between 1990 and 1995 and survived >or=1 year after the transplant. All arterial events occurring after hematopoietic stem cell transplantation (cerebral, coronary, peripheral) were reported., Results: Twenty (3.6%) out of 548 patients had a cardiovascular event in at least one arterial territory. The median age at occurrence of cardiovascular events was 54 years (range, 41-70). The cumulative incidence of a first arterial event 15 years after hematopoietic stem cell transplantation was 6% (95% CI, 3%-10%). The cumulative incidence for patients with a high global cardiovascular risk score, defined as having >or=50% of the risk factors (arterial hypertension, diabetes, dys-lipidemia, increased body-mass index, physical inactivity, smoking) was 17%, as compared to 4% in those with a low risk score. In multivariate analysis age older than 30 years at last follow-up, and a high global cardiovascular risk score were associated with, respectively, 6.4-fold and 9.8-fold increases in the risk of an arterial event., Conclusions: Long-term survivors after allogeneic hematopoietic stem cell transplantation are likely to have an increased risk of premature cardiovascular accidents.

Background and Objectives: Peripheral blood stem cells (PBSC) following reduced intensity conditioning (RIC) are being increasingly used for allogeneic transplantation in multiple myeloma. The purpose of this study was to compare outcome of patients transplanted with either PBSC or bone marrow (BM) following RIC or myeloablative conditioning (MAC)., Design and Methods: Data from 1,667 patients who had received an allogeneic identical sibling donor transplant for multiple myeloma from 1994 to 2003 were analyzed. Comparisons were made between results of PBSC and BM transplants after conditioning with RIC or MAC., Results: The engraftment rate was faster with PBSC than with BM (median: 14 and 18 days for neutrophils and 15 and 25 days for platelets respectively) irrespectively of whether RIC or MAC was used. The incidence of acute graft-versus-host disease (GVHD) did not differ significantly between the groups while chronic GVHD was more prevalent in PBSC recipients irrespectively of whether they had RIC or MAC. Non-relapse mortality did not differ between PBSC and BM recipients, but was significantly higher in those treated with MAC than in those given RIC irrespectively of the cell source. The relapse/progression rate did not differ between PBSC and BM recipients, but was significantly higher in those given RIC, irrespectively of the cell source. There was no significant difference in overall or progression-free survival between patients given PBSC or BM transplants., Interpretation and Conclusions: Although transplantation of PBSC is associated with faster engraftment and more frequent chronic GVHD, overall survival, non-relapse mortality, relapse/progression and progression-free survival are similar to those following BM transplants. However both PBSC and BM transplants are associated with lower non-relapse mortality, lower response rate and higher relapse/progression if RIC is used instead of MAC.

The introduction of imatinib mesylate has changed attitudes towards hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Information on the current use and results of HSCT is warranted. Data from 592 teams in 42 European countries described their use of HSCT for CML from 1990 to 2004. Outcomes were analyzed for 13,416 patients, with a median age of 36 years (range 1-71 years); 60% were male. The analysis considered three time cohorts, 1980 to 1990, 1991 to 1999 and 2000 to 2003. Survival, transplant-related mortality and relapse incidence were assessed at 20 years for the first cohort and compared at 2 years between the three cohorts. The numbers of HSCT for CML increased from 540 allogeneic HSCT in 1990 to 1,396 HSCT in 1999 and declined to 802 in 2004. One third of all patients and half of those with a low risk were alive at 20 years. Survival at 2 years has improved from 53% to 61% in the most recent years due to a reduction in transplant-related mortality from 41% to 30% in all patients and from 31% to 17% in low-risk patients. Stage, donor type, time interval, age and donor-recipient sex combination remain the main risk factors; patients with a risk score of 0 or 1 have a survival probability of 80% at 2 years. HSCT remains an important treatment option for patients with CML. The data describe the current status of this option and the outcome a patient can expect today. They provide an objective basis for decision making.