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Biol Blood Marrow Transplant. 2019 Feb;25(2):256-264. doi: 10.1016/j.bbmt.2018.09.001. Epub 2018 Sep 8.

Ruxolitinib Therapy Followed by Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation for Myelofibrosis: Myeloproliferative Disorders Research Consortium 114 Study.

Author information

1
MPN Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: vikas.gupta@uhn.ca.
2
Mayo Clinic Cancer Center, Phoenix, Arizona.
3
MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, BRC Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
4
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
5
Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
6
Comprehensive Cancer Center, Wake Forest School of Medicine, Winston Salem, North Carolina.
7
University of Kansas Medical Hospital, Westwood, Kansas.
8
MPN Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
9
New York University School of Medicine, New York, New York.
10
Department of Pathology, University of Utah, Salt Lake City, Utah.
11
New York Blood Center, New York, New York.
12
Memorial Sloan-Kettering Cancer Center, New York, New York.
13
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Abstract

We evaluated the feasibility of ruxolitinib therapy followed by a reduced-intensity conditioning (RIC) regimen for patients with myelofibrosis (MF) undergoing transplantation in a 2-stage Simon phase II trial. The aims were to decrease the incidence of graft failure (GF) and nonrelapse mortality (NRM) compared with data from the previous Myeloproliferative Disorders Research Consortium 101 Study. The plan was to enroll 11 patients each in related donor (RD) and unrelated donor (URD) arms, with trial termination if ≥3 failures (GF or death by day +100 post-transplant) occurred in the RD arm or ≥6 failures occurred in the URD. A total of 21 patients were enrolled, including 7 in the RD arm and 14 in the URD arm. The RD arm did not meet the predetermined criteria for proceeding to stage II. Although the URD arm met the criteria for stage II, the study was terminated owing to poor accrual and a significant number of failures. In all 19 transplant recipients, ruxolitinib was tapered successfully without significant side effects, and 9 patients (47%) had a significant decrease in symptom burden. The cumulative incidences of GF, NRM, acute graft-versus-host disease (GVHD), and chronic GVHD at 24 months were 16%, 28%, 64%, and 76%, respectively. On an intention-to-treat basis, the 2-year overall survival was 61% for the RD arm and 70% for the URD arm. Ruxolitinib can be integrated as pretransplantation treatment for patients with MF, and a tapering strategy before transplantation is safe, allowing patients to commence conditioning therapy with a reduced symptom burden. However, GF and NRM remain significant.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01790295.

KEYWORDS:

Allogeneic transplantation; GVHD; Myelofibrosis; Ruxolitinib; Survival

PMID:
30205231
PMCID:
PMC6339828
[Available on 2020-02-01]
DOI:
10.1016/j.bbmt.2018.09.001

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