[Impact of conditioning intensity on transplant outcomes following allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic neoplasms: a multicenter retrospective cohort study].

Objective: To investigate the effect of transplant conditioning intensity (TCI) on transplant outcomes in patients with myelodysplastic neoplasms (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: This multicenter retrospective cohort study included 337 patients with MDS undergoing allo-HSCT between February 2019 and April 2025 in four transplant centers in China. Patients were categorized based on TCI scores into TCI-1 (1-2 points, low intensity), TCI-2 (2.5-3.5 points, moderate intensity), and TCI-3 (4-6 points, high intensity) groups. The Fine-Gray competing risk model was applied to analyze nonrelapse mortality (NRM) and relapse. Overall survival (OS) was estimated employing the Kaplan-Meier method and compared using the log-rank test. Inverse probability of treatment weighting (IPTW) was performed to balance covariates among groups to eliminate baseline confounding bias. Furthermore, a doubly robust (DR) model combined with the Fine-Gray competing risk model was applied to assess the independent effect of TCI on NRM. Results: Unweighted analysis revealed that the 3-year NRM post-transplantation in the TCI-1, TCI-2, and TCI-3 groups was 7.7% (95% CI: 0.4%-15.1%), 8.3% (95% CI: 4.3%-12.3%), and 27.1% (95% CI: 18.0%-36.3%), respectively (P=0.008). No significant difference in the risk of NRM was observed between the TCI-1 and TCI-2 groups (sHR=1.106, 95% CI: 0.371-3.298, P=0.857), whereas the risk of NRM in the TCI-3 group was significantly higher than that in the TCI-1 (sHR=4.023, 95% CI: 1.414-11.452, P=0.009) and TCI-2 groups (sHR=3.673, 95% CI: 1.951-6.912, P<0.001). The multivariable analysis identified TCI-3, age of ≥50 years, and hematopoietic cell transplantation-comorbidity index score of >2 points as independent risk factors for NRM. After IPTW adjustment, the results remained consistent: the risk of NRM in the TCI-3 group remained significantly higher than that in the TCI-1 (sHR=6.090) and TCI-2 groups (sHR=4.562). The comparison of the contribution of NRM to transplant failure across groups at different time points revealed a significantly increased contribution of NRM to transplant failure with increasing conditioning intensity, especially in the TCI-3 group (sHR=5.011, 95% CI: 1.118-22.452, P=0.035). NRM within 3 years posttransplantation accounted for 39.0% of transplant failures. The Kaplan-Meier curve revealed that the 3-year OS rate was the lowest in the TCI-3 group (61.2%, 95% CI: 51.5%-72.7%). No statistically significant difference in the 3-year cumulative incidence of relapse was observed across the three groups. Conclusion: High-intensity conditioning failed to translate into a reduction in relapse rate but rather significantly increased the risk of NRM and compromised OS after allo-HSCT. Low- and moderate-intensity conditioning achieves a better balance between controlling toxicity and maintaining efficacy.