Survival benefit of allogeneic HSCT in CMML patients during the molecular stratification era

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for chronic myelomonocytic leukemia (CMML), yet the population benefit from HSCT and the optimal timing of HSCT remain controversial. Current guidelines, largely based on older CPSS criteria and retrospective data, may not reflect recent advances in transplant techniques and molecular stratification systems. This multicenter retrospective analysis included 389 adult CMML patients from 14 Chinese centers (2015-2023), aiming to reassess the survival benefit of allo-HSCT in a large multicenter cohort within the molecular era. Among all patients, 145 (37.3%) underwent allo-HSCT, including 68.3% from haploidentical donors. Risk stratification was performed using CPSS, MDAPS, CPSS-mol, and MMM systems. Landmark analysis set at day 148 (median transplant interval) was used to assess the effect of time-dependent covariates on long-term survival. The entire cohort had 1-, 3-, and 5-year overall survival (OS) rates of 82.7%, 55.5%, and 46.1%, respectively. In patients ≤70 years, allo-HSCT was associated with significantly improved 3-year OS in CPSS intermediate-1 (63.4% vs. 45.4%, p = 0.038) and intermediate-2 (60.2% vs. 38.7%, p = 0.049), MDAPS intermediate-1 (69.5% vs. 47.4%, p = 0.004), intermediate-2 (60.6% vs. 30.4%, p = 0.029), and high-risk (51.4% vs. 45.0%, p = 0.022), CPSS-mol intermediate-2 (59.8% vs. 39.0%, p = 0.046), and MMM high-risk groups (65.5% vs. 10.5%, p < 0.001). Landmark analysis confirmed sustained benefit in these subgroups. Haploidentical HSCT yielded outcomes comparable to matched donors. Multivariable analysis identified HSCT as an independent favorable factor for survival (HR = 0.619, p = 0.031). These findings advocate expanding transplant eligibility through integration of molecular stratification and modern HSCT platforms, particularly haploidentical protocols.