Real-world survival outcomes following allogeneic hematopoietic cell transplantation in peripheral T-cell lymphomas: A Florida multi-institutional cohort study

Abstract Introduction: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive lymphoid malignancies characterized by high relapse and mortality rates. Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended upfront for high-risk subtypes—including NK/T-cell lymphoma, hepatosplenic T-cell lymphoma (HSTCL), and adult T-cell leukemia/lymphoma (ATLL)—and recommended for relapsed or refractory nodal PTCL, including PTCL-not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). This study aims to evaluate real-world survival outcomes and prognostic factors in a Florida multi-institutional PTCL cohort treated with allo-HCT. Methods: Patients with a diagnosis of PTCL undergoing allo-HCT at Moffitt Cancer Center (MCC) and University of Miami (UM) between February 14, 2002, and April 30, 2025, were included, excluding those with cutaneous T-cell lymphoma or cord blood grafts. Data were collected through chart review and analyzed using SAS 15.3. Overall survival (OS) and progression free survival (PFS) were estimated by the Kaplan-Meier method; cumulative incidences of relapse and non-relapse mortality (NRM) by competing risks analysis. Cox proportional hazards models and Fine-Gray regression models were used to assess factors influencing survival, relapse, and NRM. Results: We identified 99 patients who received allo-HCT for PTCL at the two centers between February 2002 and April 2025. Median age at transplant was 54 (range 23–72) years; 61% were male. 71% of patients received allo-HCT at MCC and 28 patients at UM. The histology included PTCL-NOS (43%), followed by AITL (21%), anaplastic large cell lymphoma (ALCL) (13%), NK/T-cell lymphoma (9%), ATLL (6%), and other subtypes (7%). Ninety-two (93%) patients had Ann Arbor stage III–IV and 56 (57%) had primary chemo-refractory disease. 24% of patients had received an autologous stem cell transplant prior to allo-HCT. Median number of lines of therapy prior to allo-HCT was 2 (range: 1 – 8). 48 patients (48.5%) had received ≥3 prior lines of therapy. Prior to allo-HCT, 57% were in CR, 35% PR, and 8% had SD/PD. Majority (58%) received reduced-intensity conditioning (RIC). The day +30 cumulative incidence of neutrophil and platelet engraftment was 94% and 78%, respectively. Day +100 cumulative incidence of Grade II–IV acute GVHD was 44.3% (95% CI: 34.2 – 53.9). The 1-year cumulative incidence of chronic GVHD (mild–severe) was 39% [95% CI: 29%–48%] (moderate–severe 24%) Median follow-up for survivors was 59.2 months (range: 0.4–217.5). The 3-year cumulative incidence of relapse and NRM was 28% (95% CI: 20%–38%) and 25% (95% CI: 17%–34%). Median OS was 7.9 years (95% CI: 2.7 – 10.9). Median PFS was 2.5 years (95% CI: 0.7–7.9). Estimated 3- and 5-year OS was 59% (95% CI: 48%–68%) and 56% (95% CI: 45%–65%); PFS at 3 and 5 years was 47% (95% CI: 36%–56%) and 45% (95% CI: 35%–55%). On the multivariate analysis, disease status prior to transplant showed a strong association with the risk of relapse (less than CR; HR 3.8; 95% CI 1.6–9.1, p=0.003). Compared to PTCL-NOS, relapse risk was significantly higher for ATLL (p=0.0003); no significant differences were observed for extranodal NK/T-cell leukemia/lymphoma (p=0.30). On the univariate analysis for OS and PFS, no significant association was observed for age, sex, race, ECOG status at transplant, or donor type. PFS and OS with RIC were not inferior to MAC (PFS HR 0.65 [95% CI, 0.38–1.11]; OS HR 0.58 [95% CI, 0.33–1.05]). Less than CR prior to transplant was associated with worse PFS (HR 1.84, 95% CI 1.09–3.1, p=.02). Factors associated with higher risk for NRM in multivariate analysis included ECOG status ≥1 at transplant (HR 2.61, 95% CI 1.19–5.70, p=0.016). Primary chemo-refractory disease was associated with a lower risk of NRM (HR 0.42, 95% CI 0.19–0.92, p=0.029). Conclusions: Our study shows that disease status prior to allo-HCT and the lymphoma subtype are key prognostic factors for relapse after transplant. Limited performance status at transplant is predictive of worse NRM. Allo-HCT remains the primary potentially curative therapy offering long-term survival and remission for high-risk and relapsed/refractory PTCL, although significant unmet needs remain for patients with ATLL who exhibit substantially higher relapse risks.