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Biol Blood Marrow Transplant. 2016 Mar;22(3):432-40. doi: 10.1016/j.bbmt.2015.10.005. Epub 2015 Oct 19.

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors.

Author information

1
MPN Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
2
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
4
Department of Hematology and Oncology, Mayo Clinic Cancer Center, Scottsdale, Arizona.
5
Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom.
6
Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio.
7
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
8
Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York.
9
Division of Cellular Therapy and Hematologic Malignancies, Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina.
10
Oxford University Hospitals NHS trust, Oxford, UK.
11
Department of Medicine, Weill Cornell Medical College, New York, New York.
12
Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
13
Center for Cell and Gene Therapy, Baylor College of Medicine and Houston Methodist Hospital, Houston, Texas.
14
Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
15
Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio.
16
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
17
Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, Department of Leukemia, MD Anderson Cancer Center, Houston, TX, US.
18
Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada.
19
MPN Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Electronic address: vikas.gupta@uhn.ca.

Abstract

The impact of Janus kinase (JAK) 1/2 inhibitor therapy before allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into 5 groups: (1) clinical improvement (n = 23), (2) stable disease (n = 31), (3) new cytopenia/increasing blasts/intolerance (n = 15), (4) progressive disease: splenomegaly (n = 18), and (5) progressive disease: leukemic transformation (LT) (n = 13). Overall survival (OS) at 2 years was 61% (95% confidence interval [CI], 49% to 71%). OS was 91% (95% CI, 69% to 98%) for those who experienced clinical improvement and 32% (95% CI, 8% to 59%) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (P = .03), dynamic international prognostic scoring system score (P = .003), and donor type (P = .006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, 2 patients developed serious adverse events necessitating delay of HCT and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days before conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplantation outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy before HCT were particularly encouraging, and need further prospective validation.

KEYWORDS:

Allogeneic transplantation; JAK1/2 inhibitors; Myelofibrosis; Ruxolitinib; Survival

PMID:
26493563
PMCID:
PMC5030817
[Available on 2017-03-01]
DOI:
10.1016/j.bbmt.2015.10.005
[Indexed for MEDLINE]
Free PMC Article

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