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

Mohamed Shanavas, Uday Popat, Laura C. Michaelis, Veena Fauble, Donal McLornan, Rebecca Klisovic, John Mascarenhas, Roni Tamari, Murat O. Arcasoy, James Davies, Usama Gergis, Oluchi C. Ukaegbu, Rammurti T. Kamble, John M. Storring, Navneet S. Majhail, Rizwan Romee, Srdan Verstovsek, Antonio Pagliuca, Sumithira Vasu, Brenda ErnstAhmad Hanif, Richard Champlin, Paremeswaran Hari, Vikas Gupta

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)432-440
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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