Survival outcomes following second hematopoietic cell transplantation in lymphoma and leukemia: A single-center analysis

Abstract Background: Allogeneic hematopoietic cell transplantation (allo-HCT) offers curative potential for aggressive hematologic malignancies, yet relapse after a second allogeneic transplantation (allo-HCT2) remains a major limitation. This study evaluates the long-term outcomes of allo-HCT2 in patients with lymphoma and leukemia at our center, aiming to identify key prognostic factors influencing survival and transplant success. Methods: We analyzed 76 patients who underwent allo-HCT2 between 2004 and 2024, excluding 19 with other malignancies or incomplete records. Ethical approval was obtained. Clinical data were extracted from medical records. Survival was assessed using Kaplan–Meier curves and log-rank tests for overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM). Univariable Cox regression (p < 0.1) identified candidate predictors; the final model (diagnosis, age, GVHD) minimized overfitting. Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported, with multicollinearity assessed via variance inflation factors (VIFs). Cox-adjusted curves visualized diagnosis-stratified survival. Our study was approved by the Institutional Review Board at our hospital, ID: 22 KHCC 146. Results: Outcomes of 57 patients undergoing allo-HCT2 were analyzed, with 79% having lymphoma and 21% leukemia. Most recipients received reduced-intensity conditioning (89%) and sibling donors (77%). At allo-HCT2, 81% were in complete remission (CR) or had measurable residual disease (MRD). Survival analysis showed significantly worse OS (P = 0.022), relapse-free survival (RFS) (P = 0.041), and higher TRM in leukemia patients compared with lymphoma. GVHD (P = 0.014), active disease (P = 0.004), higher hematopoietic cell transplantation–specific comorbidity index (HCT-CI) scores (P = 0.004), and older age (HR = 1.09, P = 0.0048) were all negatively associated with OS. TRM was highest in leukemia patients, particularly early post-HCT. Multivariable analysis confirmed diagnosis as an independent predictor (VIFs < 3). Conclusions: Leukemia patients undergoing allo-HCT2 have significantly worse outcomes compared with lymphoma patients. Major risk factors include GVHD, active disease, higher HCT-CI scores, and older age. These findings highlight the need for risk-adapted strategies to improve survival after second allogeneic transplantation, especially for high-risk leukemia patients.