Risk Stratification of Non-Relapse Mortality After Allogeneic Hematopoietic Stem Cell Transplantation Based on Pre-Transplant Sarcopenia and HCT-CI.

Abstract

Non-relapse mortality (NRM) remains a major and often unavoidable adverse event following allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly among older adults and patients with multiple comorbidities. Although the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) is widely used for risk assessment, its predictive performance for NRM is limited, particularly for capturing functional status and physiological reserve. Sarcopenia, a marker of physical frailty and reduced physiological reserve, has recently emerged as a potential prognostic marker in transplant populations. This study aimed to determine whether combining pre-transplant sarcopenia with the HCT-CI improves NRM risk stratification after allo-HSCT. We retrospectively analyzed 95 adult patients who underwent their first allo-HSCT at our institution between May 2017 and December 2024. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria using standardized assessments of handgrip strength, gait speed, and skeletal muscle mass index. Patients were classified into high-risk (sarcopenia plus HCT-CI ≥ 3) or low-risk (others) groups. Compared with the low-risk group, the high-risk group showed significantly higher 2-year cumulative incidence of NRM (41.7% vs. 16.1%, p=0.026) and poorer overall survival (33.3% vs. 71.0%, p=0.002). In multivariable analysis, the composite high-risk classification independently predicted NRM (subdistribution hazard ratio 3.48, 95% confidence interval, 1.26-9.64, p=0.018), while sarcopenia or HCT-CI alone did not. These findings suggest that integrating physical reserve and comorbidity potentially enhances NRM risk stratification after allo-HSCT. The composite index may provide a practical framework to help optimize conditioning intensity, guide prehabilitation strategies, and personalize post-transplant management.