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Biol Blood Marrow Transplant. 2018 Nov 5. pii: S1083-8791(18)30650-5. doi: 10.1016/j.bbmt.2018.10.017. [Epub ahead of print]

Family Mismatched Allogeneic Stem Cell Transplantation for Myelofibrosis: Report from the Chronic Malignancies Working Party of European Society for Blood and Marrow Transplantation.

Author information

1
Department of Haematological Medicine,Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom. Electronic address: kavitaraj28@gmail.com.
2
Department of Medical Statistics & Bioinformatics, EBMT Statistical Unit, Leiden, The Netherlands.
3
Department of Haematological Medicine,Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
4
Department of Haematological Medicine, Hammersmith Hospital, London, United Kingdom.
5
Department of Haematology, Ospedale San Martino, Genova, Italy.
6
Department of Hematology and Hematopoietic Stem Cell Transplantation Instituto Di Ricovero e Cura a Carattere Scientificio San Raffaele Scientific Institute, Milano, Italy.
7
Department of Internal Medicine, University Hospital, Basel, Switzerland.
8
Division of Hematology, Karolinska University Hospital, Stockholm, Sweden.
9
Department of Hematology, Radboud University, Medical Centre, Nijmegen, The Netherlands.
10
Internal Medicine/Hematology, University Hospital, Uppsala, Sweden.
11
Depatment of Hematology and Bone marrow Transplantation,Rambam Medical Center, Haifa, Israel.
12
Department of Medical Statistics & Bioinformatics, EBMT Statistical Unit, Leiden, The Netherlands; Deutsche Knochenmarkspenderdatei Clinical Trials Unit, Dresden, Germany.
13
Department of Medicine, Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland.
14
Department of Oncology, Stem cell transplant unit, Medical Park Hospitals, Antalya, Turkey.
15
Department of Hematology, Instituto de investigación sanitaria Gregorio Marañon, Universidad Complutense Medicina, Madrid, Spain.
16
Departmetn of Immuno-oncolgy and Rheumatology, Universitat Bonn, Bonn, Germany.
17
Department of Onco-Hematology, Transplantation and cell therapy unit, Institut Paoli Calmettes, Marseille, France.
18
Department of Hematology, Transfusion Medicine and Biotechnology, Ospedale Civile, Pescara, Italy.
19
Institute of Hematology and Blood Transfusion, Prague, Czech Rep.
20
Department of Hematology and Bone marrow transplantation, Hopital St. Louis, Paris, France.
21
Department of Hematology, Lille University hospital INSERM U995, Universite de Lille, France.
22
Hôpitaux Universitaires de Genève, Hematology Division and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
23
Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany.

Abstract

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57 years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34+ cell dose was 4.8 × 106/kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28 days was 82% (range, 70% to 93%), at a median of 21 days (range, 19 to 23). At 2 years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100 days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.

KEYWORDS:

Haploidentical; Mismatched related donor; Myelofibrosis

PMID:
30408564
DOI:
10.1016/j.bbmt.2018.10.017

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