Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only potentially curative therapy for myelofibrosis (MF) available. However, the impact of contributing factors related to the disease, patient, and donor on the outcomes of allo-HSCT has yet to be completely explained. In addition, somatic mutations in certain genes, such as ASXL1, EZH2, SRSF2, U2AF1, and IDH1/2, are associated with worse prognosis in MF patients. Therefore, Helen Ajufo, MD, MS, Memorial Sloan Kettering Cancer Center, New York, NY, and colleagues set out to investigate the effect of clinical and molecular mutations on transplant outcomes. Their research was presented at the 2023 ASH Annual Meeting & Exposition.

The study incorporated data from 498 patients with MF across 11 centers in North America and Canada who underwent allo-HSCT between 2002 and 2021. Dr Ajufo and colleagues used a proportional-hazard Cox regression analysis stratified by each center to assess the influence of various factors on overall survival (OS). These factors encompassed several aspects, including patient features, the characteristics of the transplant itself, and disease traits. For the multivariate analysis, only baseline patient demographic data and disease characteristics were selected as covariates.

The results showed that OS rates post-transplantation were 77% (95% CI: 73-81) at 1 year and 70% (95% CI: 66-74) at 2 years, whereas nonrelapse mortality (NRM) held at 19% (95% CI: 17-21) at 1 year and 23% (95% CI: 19-27) at 2 years. The cumulative incidence (CMI) of a relapse in the patients was 12% (95% CI: 10-14) and 16% (95% CI: 12-20) 1 and 2 years after the procedure, respectively. In addition, the CMI of acute graft versus host disease (aGVHD) grade II-IV was at a rate of 31% (95% CI: 27-35) at 3 months and 42% (95% CI: 38-46) at 1 year after transplantation. For aGVHD grade III-IV, the rate was 13% (95% CI: 11-15) and 18% (95% CI: 14-22), respectively. 

The authors also investigated the incidence of neutrophil and platelet engraftment in the post-transplant period. For neutrophils, the CMI was 90% (95% CI: 87-93) at 1 month and 97% (95% CI: 95-95)  at 3 months. For platelets, the corresponding percentages were 55% (95% CI: 50-59) and 80% (95% CI: 76-83). From a genetic perspective, it appeared that mutations in the ZRSR2 gene result in reduced overall survival. However, other mutations, including the more common JAK2, did not show a significant influence on OS.

Notably, the authors found that splenomegaly (an enlarged spleen) does not impact the OS but is strongly associated with the rate of engraftment. In terms of donor-related variables, mismatched unrelated and haploidentical donors also did not impact survival rates negatively but were associated with a delay in platelet engraftment.

Upon conducting a multivariate analysis—adjusting for factors such as age, gender, highest score on the Dynamic International Prognostic Scoring System (DIPSS), donor type, and conditioning regimen—it was determined that having platelet counts higher than 50 × 109/L (HR of .61), hemoglobin levels more than 10 g/dL (HR of .6), and a lower DIPSS score at the time of the transplant were all factors that contributed to an improved OS outcome in the patients. 

The study’s findings suggest that while allo-HCT remains the only potentially curative treatment for MF patients, the results of the treatment are primarily dependent on clinical variables. The research also lays a foundation for future research in understanding the effects of donor types and conditioning regimens on the results of allo-HCT.

Ajufo H, Derkach A, Rampal RK, et al. Clinical Factors but Not Somatic Mutations Predict for Survival in Patients with Myelofibrosis Undergoing Allogeneic Hematopoietic Cell Transplant: Analysis of the North American Myelofibrosis Transplant Outcome (NAMTO) Study. Presented at: the 2023 ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA, and virtual; Abstract 3181.