Background: Allogenic hematopoietic stem cell transplantation (AHSCT) for myelofibrosis (MF) patients (pts) can involve several disease-specific challenges, including increased patient age and low performance status, medical comorbidities resulting from MF, delayed engraftment, and graft-versus-host disease (GVHD). Several strategies exist to minimize these difficulties, including donor type (HLA-matched versus mismatched), conditioning regimen, and GVHD prophylaxis. The use of post-transplant cyclophosphamide has decreased the incidence of GVHD in HLA-mismatched transplants, but pts with MF were excluded from most GVHD prevention studies. We evaluated outcomes of pts at our center who underwent AHSCT for MF.

Methods: The study population included adult pts with diagnosis of primary or secondary MF who underwent AHSCT between 2005 and 2024 at Karmanos Cancer Institute. We assessed associations between six variables (age, conditioning regimen, HLA match status, GVHD prophylaxis, CD 34+ve cell dose and Karnofsky performance status (KPS)) on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse-free survival (RFS), overall survival (OS), relapse, and non-relapse mortality (NRM).

Results: We identified 69 pts. 23 pts (33.3%) had secondary MFB. 46 pts (66.7%) received a reduced-intensity conditioning (RIC) regimen and 23 pts (33.3%) received a myeloablative conditioning (MAC) regimen. 44 pts (63.8%) had fully matched donor (MD) and 25 pts (36.2%) had mismatched donors (MMD). 12 pts (17.4%) received post-transplant cyclophosphamide while 57 pts (82.6%) received calcineurin inhibitor based regimen with or without thymoglobulin. With median follow-up of 5.03 years, the median overall survival (OS) was 12.5 years (95% CI 1.7-NE) with OS at 2 years being 59.4% (95% CI 48.6-72.5). The cumulative incidences of grade II-IV and III-IV aGVHD at 100 days were 26.4% (95% CI 16.5-37.3) and 10.3% (95% CI 4.5-18.9), respectively. The cumulative incidence of extensive cGVHD at 1 year was 30.3% (95% CI 19.6-41.7). The cumulative incidences of relapse and NRM at 1 year were 7.4% (95% C1 2.7-15.3) and 28.2% (95% CI, 18.0-39.3), respectively.

In multivariable analysis, we observed that:

  • Pts with MMD had a significantly higher risk of death compared to those with MD (HR 3.42; 95% CI 1.4-8.34; p=0.007).

  • Pts with MMD had a significantly higher risk of death or disease relapse (HR 3.38; 95% CI 1.41-8.09; p=0.006).

  • Pts with MMD had a significantly higher risk of NRM compared to those with MD (HR 4.69; 95% CI 1.63-13.49; p = 0.004).

  • Pts with KPS<80 had significantly higher risk of developing aGVHD (HR 2.45; 95% CI 1.11-5.42; p=0.027).

Conclusions: Our analysis shows that pts with MMD had significantly higher risk of death, disease relapse, and NRM than those with MD. In addition, pts with KPS<80 had significantly higher risk of developing aGVHD. With a limited number of pts who received post-transplant cyclophosphamide, we did not observe a significant difference in aGVHD, cGVHD, NRM, relapse, RFS or OS compared to other GVHD prevention strategies.

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2025
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