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Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group

Abstract

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.

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Correspondence to G Barosi.

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NMK declares speakers’ bureau and research funding from Sanofi and Novartis; FC declares consulting and speakers’ bureau from Novartis, AOP and Baxter; DM declares honoraria, speakers’ bureau and research funding from Novartis; AR declares consulting from Piere Fabre Pharma, and Travels from Piere Fabre Pharma and Novartis; EO declares travel expenses for Novartis, Bristol Meyers Squibb and Sanofi; CH declares honoraria and speakers’ bureau from Novartis, Sanofi and Shire. GB declares consulting from Celgene; DN declares speakers’ bureau and travels from Novartis; TB declares consulting, speakers’ bureau from Novartis and Shire; RM declares honoraria and consulting from Novartis, and funding from Incyte, Gilead, Genentech; VG declares honoraria, consulting, and research funding from Novartis and Incyte; AMV declares consulting and speakers’ bureau from Novartis; MD declares consulting from MSD Sharp and Dohme, and research funding from Biosciences; URP declares research funding from CTI Pharma and Otsuka; DR declares consulting from Incyte, and speakers’ bureau from Sanofi. The remaining authors declare no conflict of interest.

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NMK and GB designed the research; GB did the systematic review of literature; NMK, JHD, EO, AB and DN wrote the first draft of the recommendations; TB, AR, RM, AT, MG, VG, CH, HA, AMV, FC, MR, MD, VF, DM, KB, URP, FP and DR criticized the first draft of the recommendations and provided important input in the text of the recommendations; GB wrote the first draft of the manuscript; and all the authors approved the final version of the manuscript.

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Kröger, N., Deeg, J., Olavarria, E. et al. Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group. Leukemia 29, 2126–2133 (2015). https://doi.org/10.1038/leu.2015.233

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