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The aim of this work is to produce recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles released from 1999 to 2015 (January) was used as a source of scientific evidence. Recommendations were produced using a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention and management of relapse after transplant. Patients with intermediate-2- or high-risk disease and age <70 years should be considered as candidates for allo-SCT. Patients with intermediate-1-risk disease and age <65 years should be considered as candidates if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood (PB) >2%, or adverse cytogenetics. Pre-transplant splenectomy should be decided on a case by case basis. Patients with intermediate-2- or high-risk disease lacking an human leukocyte antigen (HLA)-matched sibling or unrelated donor, should be enrolled in a protocol using HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants. The optimal intensity of the conditioning regimen still needs to be defined. Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte infusion or both were deemed appropriate to avoid clinical relapse. In conclusion, we provided consensus-based recommendations aimed to optimize allo-SCT in PMF. Unmet clinical needs were highlighted.

Synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid malignancies have remained elusive. RNA-interference drug modifier screens identified antiapoptotic BCL-2 family members as potent 5-Azacytidine-sensitizing targets. In further dissecting BCL-X L , BCL-2 and MCL-1 contribution to 5-Azacytidine activity, siRNA silencing of BCL-X L and MCL-1, but not BCL-2, exhibited variable synergy with 5-Azacytidine in vitro . The BCL-X L , BCL-2 and BCL-w inhibitor ABT-737 sensitized most cell lines more potently compared with the selective BCL-2 inhibitor ABT-199, which synergized with 5-Azacytidine mostly at higher doses. Ex vivo , ABT-737 enhanced 5-Azacytidine activity across primary AML, MDS and MPN specimens. Protein levels of BCL-X L , BCL-2 and MCL-1 in 577 AML patient samples showed overlapping expression across AML FAB subtypes and heterogeneous expression within subtypes, further supporting a concept of dual/multiple BCL-2 family member targeting consistent with RNAi and pharmacologic results. Consequently, silencing of MCL-1 and BCL-X L increased the activity of ABT-199. Functional interrogation of BCL-2 family proteins by BH3 profiling performed on patient samples significantly discriminated clinical response versus resistance to 5-Azacytidine-based therapies. On the basis of these results, we propose a clinical trial of navitoclax (clinical-grade ABT-737) combined with 5-Azacytidine in myeloid malignancies, as well as to prospectively validate BH3 profiling in predicting 5-Azacytidine response.

At present, allo-SCT is the only curative treatment for patients with myelofibrosis (MF). Unfortunately, a significant proportion of candidate patients are considered transplant ineligible due to their poor general condition and advanced age at the time of diagnosis. The approval of the first JAK inhibitor, ruxolitinib, for patients with advanced MF in 2011 has had a qualified impact on the treatment algorithm. The drug affords substantial improvement in MF-associated symptoms and splenomegaly but no major effect on the natural history. There has, therefore, been considerable support for assessing the drug’s candidacy in the peritransplant period. The drug’s precise impact on clinical outcome following allo-SCT is currently not known; nor are the drug’s long-term efficacy and safety known. Considering the rarity of MF and the small proportion of patients who undergo allo-SCT, well designed collaborative efforts are required. In order to address some of the principal challenges, an expert panel of laboratory and clinical experts in this field was established, and an independent workshop held during the 54th American Society of Hematology Annual Meeting in New Orleans, USA on 6 December 2013, and the European Hematology Association's Annual Meeting in Milan, Italy on 13 June 2014. This document summarizes the results of these efforts.

This pilot 2-week, randomized controlled trial examined integrating digital storytelling (DST) with heart rate variability biofeedback (HRVB) to enhance psycho-emotional well-being of hematopoietic cell transplantation (HCT) patients. HCT patients ( N = 25; M age = 51.9 years) were randomly assigned: (1) DST + HRVB intervention, or (2) DST-only control. Both groups viewed four emotionally-rich digital stories. The DST + HRVB group practiced HRVB at home for ten minutes/day. DST + HRVB participants decreased anger, depression, fatigue ( d = 0.53) and increased emotional processing ( d = 0.20), and HRV-assessed autonomic nervous system balance (3.5 vs. 0.9). This study supports feasibility of integrating DST with HRVB, and effect sizes indicate superiority of combining DST with HRVB.

At present, allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only curative treatment for patients with myelofibrosis (MF). Unfortunately a significant proportion of candidate patients are considered transplant ineligible due to their poor general condition and advanced age at time of diagnosis. The approval of the first JAK inhibitor, Ruxolitinib, for patients with advanced MF in 2011 has had a qualified impact on the treatment algorithm. The drug affords substantial improvement in MF-associated symptoms and splenomegaly but no major effect on the natural history. There has, therefore, been considerable support to assess the drug’s candidacy in the peri-transplant period. The drug’s precise impact on clinical outcome following allo-SCT is currently not known; nor is the drug’s long term efficacy and safety known. Considering the rarity of MF and the small proportion of patients who are undergoing allo-SCT, well designed collaborative efforts are required. In order to address some of the principal challenges, an expert panel of laboratory and clinical experts in this field was established, and an independent workshop held during the 54th American Society of Hematology’s meeting in New Orleans, USA, on 6th December 2013 and the European Hematology Association meeting in Milan, Italy on 13th June 2014. This document summarizes the results of these efforts.

The myeloproliferative neoplasm, myelofibrosis (MF), has only one therapeutic intervention that is potentially curative in these individuals, specifically that of allogeneic stem cell transplantation (ASCT). ASCT has been utilized up to this juncture, primarily in younger individuals with higher risk disease. There is more limited data on outcomes in individuals over the age of 60 years. The choice of an individualized therapeutic intervention for a patient with MF is a very complex issue and is dependent on several factors. The first factor being their overall prognosis with their illness (which can vary from a median of 2 years in high-risk patients to over 10 years in low-risk patients) and the potential impact of a therapeutic intervention not only on survival but also on quality of life. Current available therapies have been strictly palliative for disease-associated anemia and/or splenomegaly. At present, we have a new generation of inhibitors of JAK2 (Ruxolitinib, CYT387, SB1518, TG101348, with others in development), which have been shown to improve splenomegaly, improve symptomatic burden of illness and improve quality of life. In addition, these inhibitors of JAK2 may have an impact on the natural history of MF, but confirmation of the presence and degree of this impact is still pending. Clinical availability of JAK2 inhibitors may alter the timing of transplant in marginal transplant candidates (that is, those over the age of 60), may have a role preceding ASCT to improve spleen size and performance status before transplant and might be frontline therapy in intermediate and high-risk patients who are not candidates for ASCT.