Prognostic impact of transplant conditioning intensity (TCI) score and minimal identifiable disease (MID) in MDS: A multicenter trophy group study

Abstract

Abstract Background: Due to the heterogeneity of myelodysplastic syndromes (MDS) and variations in patient characteristics, the optimal conditioning intensity remains undetermined. Transplant Conditioning Intensity (TCI) score—previously validated in AML offers a more nuanced classification , establishing an intermediate category distinct from myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC). TCI has demonstrated significant superiority in predicting treatment-related mortality (TRM) and relapse; In this study, we evaluated TCI score in MDS to optimize individualized conditioning regimen selection for MDS transplantation Methods: We retrospectively analyzed 230 adult MDS patients undergoing allogeneic HSCT within the TROPHY group. Conditioning intensity was categorized using the TCI score (Low, Intermediate, High) and compared to standard MAC/RIC classification. Two-year outcomes included Overall Survival (OS), Relapse-Free Survival (RFS), Non-Relapse Mortality (NRM), and Cumulative Incidence of Relapse (CIR). Key covariates assessed were pre-HSCT Minimal Identifiable Disease (MID) status (defined by cytogenetic abnormality or flow cytometry positivity) and patient age. Results: Consistent with known limitations of MAC/RIC, no significant prognostic differences were observed between MAC and RIC overall. Similarly, TCI categories showed no significant difference in OS (High vs. Intermediate vs. Low: 83.1% vs. 68.9% vs. 74.0%, P=0.13), RFS (78.4% vs. 64.0% vs. 68.4%, P=0.15), NRM (9.2% vs. 22.3% vs. 12.5%, P=0.06), or CIR (12.3% vs. 13.7% vs. 19.1%, P=0.50). Older patients (≥50y) had significantly inferior OS (P=0.004), RFS (P=0.003), and higher NRM (P=0.003) compared to younger patients. Notably, High TCI intensity did not improve outcomes for older patients; Intermediate/Low TCI intensities were associated with better outcomes in this age group compared to High TCI. Among 220 evaluable patients, 137 (62.3%) had <5% marrow blasts at HSCT; of these, 45 (32.8%) were MID-positive and 86 (62.8%) MID-negative. MID-positive status was strongly associated with significantly shorter OS (2y-OS: 61.9% vs. 88.9%, P<0.001), RFS (55.3% vs. 81.4%, P=0.001), higher NRM (20.0% vs. 7.3%, P=0.034), and higher CIR (24.7% vs. 11.3%, P=0.0498). The TCI score revealed critical interactions: 18 (40.0%) in the MID-positive group received High TCI intensity and 24 (53.3%) received Intermediate TCI. High TCI intensity significantly improved RFS (vs. MID-negative: 72.2% vs. 86.7%, P=0.22) and reduced CIR (16.7% vs. 8.9%, P=0.42) specifically for MID-positive patients compared to Intermediate TCI. Within the MID-positive group, Intermediate TCI showed only a trend towards improved NRM (29.2% vs. 13.3%, P=0.18). These interactions were not identified using traditional MAC/RIC subgroup analyses. Conclusion: This study confirms the strong prognostic significance of pre-HSCT MID status in MDS. The TCI score provides a more nuanced assessment of conditioning intensity than the binary MAC/RIC system, revealing critical interactions obscured by traditional classification. High-intensity conditioning (High TCI) benefits MID-positive patients but appears detrimental for older patients, where reduced intensity (Intermediate/Low TCI) confers a survival advantage. These findings support using the TCI score alongside disease burden (MID) and patient age to optimize individualized conditioning regimen selection for MDS transplantation.