Myeloablative and Reduced Intensity Allogeneic Transplant in Patients with Myeloproliferative Neoplasms.

Abstract

Background: Allogeneic hematopoietic cell transplant (allo-HCT) is the only potentially curative treatment for myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML). Older age, comorbidities, and often advanced disease make patient selection and optimal transplant timing challenging. This study sought to understand allo-HCT outcomes for these myeloproliferative neoplasms in a contemporary era, including molecular data, to define a uniform transplant approach.

Methods: Retrospective analysis was performed on patients with MF or CMML who received allo-HCT at the Cleveland Clinic between January 1, 2010 and April 1, 2023. All donor types and graft sources were included. MF and CMML outcomes were analyzed separately.

Results: Fifty-nine MF and 33 CMML patients were included. JAK2 V617F was detected in 57.6% of MF patients; only 34 (57.6%) had next-generation sequencing (NGS) performed. Most MF transplants were reduced intensity (RIC; 69.5%) and peripheral blood stem cell (PBSC; 91%). At median follow-up of 41 months, 28/59 (47.5%) MF patients were alive. MF patients who were JAK2+ with additional cytogenetic changes or concurrent mutations had better overall survival. In CMML, 69.7% had myeloid NGS, with ASXL1 identified in 51.9% of cases. Most transplants were RIC (66.7%) and PBSC (72.7%). At median follow-up of 46.8 mos, 13/33 (39.4%) patients were alive. Relapse accounted for 9/20 CMML deaths; 8 of these received RIC. Mutational signature did not significantly impact survival, though the presence of any cytogenetic aberrancy was associated with worse OS (12 mos, 95% CI, 7.13-NA vs. 24.2 mos, 9.6-NA; P = 0.19).

Conclusion: For MF and CMML, older patients (≥65) and RIC transplants trended toward worse survival. Strategies to reduce relapse and optimize patient selection utilizing molecular and cytogenetic data should be considered.