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

Autor: Shanavas M; MPN Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Popat U; Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas., Michaelis LC; Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Fauble V; Department of Hematology and Oncology, Mayo Clinic Cancer Center, Scottsdale, Arizona., McLornan D; Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom., Klisovic R; Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio., Mascarenhas J; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York., Tamari R; Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York., Arcasoy MO; Division of Cellular Therapy and Hematologic Malignancies, Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina., Davies J; Oxford University Hospitals NHS trust, Oxford, UK., Gergis U; Department of Medicine, Weill Cornell Medical College, New York, New York., Ukaegbu OC; Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Kamble RT; Center for Cell and Gene Therapy, Baylor College of Medicine and Houston Methodist Hospital, Houston, Texas., Storring JM; Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada., Majhail NS; Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio., Romee R; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri., Verstovsek S; Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, Department of Leukemia, MD Anderson Cancer Center, Houston, TX, US., Pagliuca A; Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom., Vasu S; Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio., Ernst B; Department of Hematology and Oncology, Mayo Clinic Cancer Center, Scottsdale, Arizona., Atenafu EG; Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada., Hanif A; Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Champlin R; Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas., Hari P; Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Gupta V; MPN Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Electronic address: vikas.gupta@uhn.ca.
Jazyk: angličtina
Zdroj: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2016 Mar; Vol. 22 (3), pp. 432-40. Date of Electronic Publication: 2015 Oct 19.
DOI: 10.1016/j.bbmt.2015.10.005
Abstrakt: 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.
(Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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