Myeloablative and Reduced Intensity Allogeneic Transplant in Patients with Myeloproliferative Neoplasms

Area of Science:

• Hematology
• Oncology
• Stem Cell Transplantation

Background:

• Allogeneic hematopoietic cell transplant (allo-HCT) is a potentially curative treatment for myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML).
• Patient selection and transplant timing are challenging due to older age, comorbidities, and advanced disease.
• This study investigates contemporary allo-HCT outcomes for MF and CMML, incorporating molecular data to refine treatment approaches.

Purpose of the Study:

• To analyze outcomes of allogeneic hematopoietic cell transplant (allo-HCT) for myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML) in a contemporary patient cohort.
• To evaluate the impact of molecular and cytogenetic data on allo-HCT outcomes.
• To inform the development of a uniform transplant strategy for these hematologic malignancies.

Main Methods:

• Retrospective analysis of MF and CMML patients undergoing allo-HCT at Cleveland Clinic (January 2010 - April 2023).
• Inclusion of all donor types and graft sources.
• Separate analysis of outcomes for MF and CMML, including next-generation sequencing (NGS) data.

Main Results:

• Fifty-nine MF patients (47.5% alive at median 41 months) and 33 CMML patients (39.4% alive at median 46.8 months) were analyzed.
• JAK2 V617F mutation was common in MF; molecular data (JAK2+, additional mutations) correlated with better MF survival.
• In CMML, ASXL1 mutations were frequent; cytogenetic abnormalities were associated with worse overall survival, and relapse was a significant cause of death, particularly after reduced-intensity conditioning (RIC).

Conclusions:

• Older patients (≥65) and those receiving reduced-intensity conditioning (RIC) allo-HCT for MF and CMML trended towards worse survival.
• Strategies incorporating molecular and cytogenetic data are crucial for optimizing patient selection.
• Further research should focus on reducing relapse rates and refining transplant approaches for MF and CMML.