Pre-transplant JAK-inhibition improves post-transplant outcome in myelofibrosis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative approach in myelofibrosis (MF). Janus-Associated Kinase inhibitors (JAKi) have changed the treatment paradigm of MF patients, becoming a therapeutic mainstay in those with splenomegaly and/or constitutional symptoms. The impact of JAKi prior to allogeneic transplant is still under investigation. The aim of the current study was to analyze the outcome and prognostic factors, especially JAKi impact on transplantation outcome in MF patients. The study comprised 96 patients (64 - MF, 21 - post-polycythemia vera (PV), 11 - post-essential thrombocythemia (ET) at a median age of 54 years at transplant (44 females, 52 males) who underwent alloHSCT in years 2008-2025. Forty-seven patients (49%) had previously received JAKi with a median treatment duration of 11 months. Median follow-up after alloHSCT was 11 months. A 2-year probability of overall survival (OS) was 78.5% for JAKi exposed patients and 48.2% for JAKi naïve ones (p = 0.005), event free survival (EFS) was 70.0% and 46.2%, respectively (p = 0.02). A 2-year relapse incidence (RI) was 13.7% and 22.6% (p = 0.298) and non-relapse mortality (NRM) was 18.9% and 40.3% (p = 0.033) in JAKi and no-JAKi exposed group, respectively. Prior JAKi use was the only factor favorably impacting post-transplant overall survival both in uni- and multivariable analysis (p = 0.02 and p = 0.03, respectively). Low ECOG score and low HCT-CI positively affected survival. Transfusion dependency prior to alloHSCT was identified as an unfavorable factor. It was demonstrated that pre-transplant JAK inhibition significantly improved post-transplant overall survival. Patient's performance status and comorbidities are variables significantly affecting survival. Transfusion burden not only adversely impacts quality of life but was also found as an adverse factor in terms of EFS, NRM and RI.