A single-institution retrospective analysis of allo-HSCT for relapsed and refractory aggressive lymphomas: T-cell origin predicts better outcomes even in active disease.

Abstract Introduction: Relapsed and refractory (r/r) aggressive lymphoma remains a therapeutic challenge. In recent years, chimeric antigen receptor-T cell (CAR-T) therapy has significantly improved outcomes in B-cell lymphomas, leading to a reduced reliance on allogeneic hematopoietic stem cell transplantation (allo-HSCT) for these patients. In contrast, allo-HSCT remains a frequently selected treatment option for patients with r/r T-cell lymphomas. However, it remains unclear which specific histological subtypes benefit the most from allo-HSCT, and whether particular subtypes respond favorably to allo-HSCT even when patients present with stable disease (SD) or progressive disease (PD) at the time of transplantation. Methods: We conducted a single-institution retrospective analysis of 92 patients who underwent their first allo-HSCT for large B-cell lymphoma (LBCL) and nodal peripheral T-cell lymphoma (PTCL) at Toranomon Hospital between February 2011 and December 2023. The primary endpoints were overall survival (OS) and progression-free survival (PFS) following allo-HSCT. Secondary endpoints included non-relapse mortality (NRM) and relapse rate (RR) following allo-HSCT. OS and PFS probabilities were estimated using the Kaplan-Meier method, and differences were evaluated with the log-rank test. Cox regression models were used to assess the independent effect of lymphoma subtype (LBCL vs PTCL) on outcomes, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated. The Fine-Gray model was used to analyse relapses, NRM, and acute graft-versus-host disease (aGVHD), accounting for competing risks. Results: Among the 92 patients, 59 had LBCLs, and 33 had PTCLs. The median age at allo-HSCT was 51 years (range, 30-70), with 30% of patients being female. A total of 64 patients (69.6%) had a performance status of 0 or 1. At transplantation, 54 patients (58.7%) had SD or PD. Seventy-one patients (77.2%) had undergone cord blood transplantation. LBCL subtypes included 49 cases of diffuse large B-cell lymphoma, 8 cases of high-grade B-cell lymphoma, and 2 cases of primary mediastinal large B-cell lymphoma. PTCL subtypes included 20 cases of peripheral T-cell lymphoma, not otherwise specified, 10 of angioimmunoblastic T-cell lymphoma, and 3 of ALK-negative anaplastic large cell lymphoma. The median follow-up among survivors was 7.6 years (range, 0.8 - 12.4). The 5-year OS and PFS were 31.6% (95% CI, 22.3 - 41.4%) and 27.9% (95% CI, 18.9 - 37.6%), respectively. The 5-year NRM was 30.8% (95% CI, 21.6 - 40.4%), and the 5-year RR was 41.3% (95% CI, 30.9 - 51.3%). There were no significant differences in age between the LBCL and PTCL cohorts (median age: 50 vs 51 years; p = 0.84). The proportions of patients with SD or PD at transplantation did not significantly differ between LBCL and PTCL (59% vs. 58%; p = 1.00). A greater proportion of LBCL patients had received prior autologous HSCT compared to PTCL patients (34% vs 12%; p = 0.03). Among the LBCL patients, two underwent allo-HSCT following CAR-T therapy with lisocabtagene maraleucel. The 5-year OS and PFS were significantly higher in the PTCL group compared to the LBCL group (OS: 47.7% vs. 22.4%, p=0.03; PFS: 39.7% vs. 21.0%, p=0.03). The 5-year CI of RR was also significantly higher in LBCL than in PTCL (49.5% vs 26.9%; P=0.02). The 5-year CI of NRM did not differ between the groups (LBCL: 29.4% vs. PTCL: 33.3%; P = 0.50). The 100-day CI of aGVHD was comparable (LBCL: 67.1% vs PTCL: 63.6%; P = 0.94). Both PTCL and LBCL showed distinct survival patterns following allo-HSCT. In PTCL, the 5-year OS was 63.5% for patients in CR/PR, and 36.1% for those in SD/PD (p = 0.15). In LBCL, survival was significantly worse in SD/PD compared to CR/PR, with 5-year OS of 12.7% vs. 36.4% (p = 0.04). Notably, PTCL patients with SD/PD had comparable OS to LBCL patients with CR/PR (36.1% vs. 36.4%).Multivariate analysis confirmed that lymphoma subtype (LBCL vs PTCL) was independently associated with improved OS (HR, 0.56; 95% CI, 0.32-0.97; P = 0.04) and PFS (HR, 0.56; 95% CI, 0.33-0.94; P = 0.03). Conclusion: This analysis of patients undergoing first allo-HSCT for r/r aggressive lymphoma suggested that PTCL may derive greater benefit from allo-HSCT than LBCL. Notably, patients with PTCL demonstrated favorable long-term outcomes even when undergoing allo-HSCT with SD or PD. These findings support the potential utility of allo-HSCT as a more effective therapeutic option for PTCL compared to LBCL.