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State-of-the-art review: allogeneic stem cell transplantation for myelofibrosis in 2019
Donal P. McLornan,1,2 Ibrahim Yakoub-Agha,3 Marie Robin,4 Yves Chalandon,5 Claire N. Harrison1,2* and Nicolaus Kroger6*
ABSTRACT
Advances in understanding the pathogenesis and molecular land- scape of myelofibrosis have occurred over the last decade. Treating physicians now have access to an ever-evolving arma- mentarium of novel agents to treat patients, although allogeneic hematopoietic stem cell transplantation remains the only curative approach. Improvements in donor selection, conditioning regimens, dis- ease monitoring and supportive care have led to augmented survival after transplantation. Nowadays, there are comprehensive guidelines concern- ing allogeneic hematopoietic stem cell transplantation for patients with myelofibrosis. However, it commonly remains difficult for both physi- cians and patients alike to weigh up the risk-benefit ratio of transplanta- tion given the inherent heterogeneity regarding both clinical course and therapeutic response. In this timely review, we provide an up-to-date synopsis of current transplantation recommendations, discuss usage of JAK inhibitors before and after transplantation, examine donor selection and compare conditioning platforms. Moreover, we discuss emerging data concerning the impact of the myelofibrosis mutational landscape on transplantation outcome, peri-transplant management of splenomegaly, poor graft function and prevention/management of relapse.
Introduction
Myelofibrosis is a heterogeneous disease as regards both disease phenotype and mutational landscape. Following the discovery of the JAK2V617F mutation in 2005 and subsequent studies confirming the clinical efficacy of JAK inhibitors, the treat- ment paradigm has been revolutionized.1-6 Worldwide experience with JAK inhibitor therapy continues to grow and a considerable proportion of patients will gain beneficial symptom and/or splenic responses, albeit heterogeneous and of variable duration. Furthermore, given that many other novel therapeutics, such as anti-fibrotic and immunomodulatory agents, have been used to treat myelofibro- sis,7 the majority of patients moving forward with allogeneic hematopoietic stem cell transplantation (SCT) have had at least one prior treatment, making ‘real- world’ transplant decisions increasingly complex. Data from the European Society for Blood and Marrow Transplantation (EBMT) suggest a year-on-year increase in transplants for myelofibrosis. In this review we focus on current indications for allogeneic SCT, prognostic scoring models to aid decision-making, donor selec- tion, conditioning regimens, the role of splenectomy and prevention and manage- ment of relapse.
Ferrata Storti Foundation
Haematologica 2019 Volume 104(4):659-668
1Guy’s and St.Thomas’ NHS Foundation Trust, Department of Haematology, Guy’s Tower, Great Maze Pond, London, UK; 2Comprehensive Cancer Centre, King’s College, London, UK; 3CHU de Lille, LIRIC, INSERM U995, Universite de Lille, France; 4Hôpital Saint-Louis, Service d'Hématologie-Greffe, Assistance Publique Hôpitaux de Paris, University Paris 7, INSERM 1131, France; 5Geneva University Hospitals, Division of Hematology, Rue Gabrielle- Perret-Gentil 4 and Faculty of Medicine, University of Geneva, Switzerland and 6University Hospital Eppendorf, Hematology Department, Hamburg, Germany
CNH and NK: joint senior authors
Correspondence:
DONAL P MCLORNAN
donal.mclornan@nhs.net
Received: September 9, 2018. Accepted: November 16, 2018. Pre-published: March 14, 2019.
doi:10.3324/haematol.2018.206151
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/4/659
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