Outcomes of allogeneic hematopoietic cell transplantation in myelofibrosis using post-transplant cyclophosphamide-based gvhd prophylaxis

Abstract Background Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelofibrosis (MF), though outcomes remain variable. Recent EBMT data demonstrate improved overall survival (OS) with matched sibling donors. However, the influence of pre-transplant clinical factors on transplant outcomes requires further research. We aimed to evaluate post-HCT outcomes and their association with baseline clinical characteristics in a diverse MF cohort receiving post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis. Methods Aretrospective multicenter analysis was conducted on patients with MF who underwent allo-HCT with PTCy-based prophylaxis (2013-2019) using Center for International Blood and Marrow Transplant Research (CIBMTR) registry data (P-5956, Jain et al., 2023). We evaluated the impact of recipient- and disease-related variables on outcomes, including overall survival (OS), relapse, non-relapse mortality (NRM), graft rejection, acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), and neutrophil and platelet engraftment. Variables included recipient age, sex, race, Karnofsky performance score, Dynamic International Prognostic Scoring System (DIPSS) risk category, Sorror comorbidity index, prior ruxolitinib use, CMV donor-recipient serostatus, conditioning intensity, and splenic interventions. Univariable and multivariable Cox regression models were used, with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. All statistical analyses were performed using Stata 18, with statistical significance defined as p < 0.05. Results A total of 216 patients were included, with a median age of 60.4 ± 8.9 years; 128 (59%) were male. Underlying diagnoses included primary MF in 149 (69%) and polycythemia vera in 64 (30%) patients. Karnofsky performance status was ≥90 in 122 (57%) patients. The median Sorror comorbidity score was 2.5 ± 2.0, and 104 (48%) patients had an HCT-CI score of 3–4. DIPSS risk prior to transplant was intermediate-2 in 82 (38%), intermediate-1 in 75 (35%), and low in 26 (12%) patients. Race/ethnicity was reported as White in 157 (73%), Black in 20 (9%), Asian in 7 (3%), and Other in 32 (15%) patients. The 2-year OS was 59.7%, with relapse in 52.8%, NRM in 25.0%, and graft rejection in 14.4%. On univariable analysis, splenic radiation was associated with inferior OS (HR 6.76, 95% CI 2.09–21.84; p=0.001), TRM (HR 7.62, 95% CI 2.34–24.78; p=0.001), and aGVHD (HR 7.16, 95% CI 2.22–23.17; p=0.001). Higher Sorror comorbidity score predicted increased TRM (HR 1.20, 95% CI 1.06–1.35; p=0.005). Female sex was associated with an increased TRM (HR 1.44, 95% CI 1.08–1.92; p = 0.012) and a lower risk of cGVHD (HR 0.62, 95% CI 0.37–1.02; p = 0.062). Graft rejection was more likely among patients of Asian race (HR 3.15, 95% CI 0.92–10.82; p=0.068), “Other” race (HR 11.06, 95% CI 2.52–48.48; p=0.001), and those with high DIPSS (HR 7.20, 95% CI 1.01–51.16; p=0.049). In multivariable analysis, splenic radiation remained significantly associated with aGVHD (HR 9.46, 95% CI 2.01–44.48; p = 0.004). Higher Sorror comorbidity score was also associated with inferior OS (HR 1.33, 95% CI 1.09–1.64; p=0.005) and TRM (HR 1.39, 95% CI 1.12–1.72; p=0.003). Female sex was associated with a reduced risk of cGVHD (HR 0.48, 95% CI 0.26–0.87; p = 0.015) and an increased risk of TRM (HR 1.69, 95% CI 1.10–2.60; p = 0.017). Graft rejection remained significantly associated with Asian race (HR 7.58, 95% CI 1.81–31.68; p=0.006), “Other” race (HR 11.16, 95% CI 1.70–73.51; p=0.012), and high DIPSS (HR 16.07, 95% CI 1.43–180.22; p=0.024). Conclusions In patients with myelofibrosis undergoing allogeneic transplantation with post-transplant cyclophosphamide, recipient and disease characteristics, including comorbidity score, sex, prior splenic radiation, and DIPSS risk, were significantly associated with overall survival, transplant-related mortality, graft rejection, and graft-versus-host disease. These findings underscore the importance of incorporating clinical and disease-specific factors into transplant planning and donor selection to enhance outcomes.