Hematopoietic stem cell transplantation in T-cell lymphomas: A promising strategy challenging poor prognosis

Abstract Introduction: T-cell lymphomas (TCLs) are a rare and aggressive entity, with a higher prevalence in Latin America and Asia. The most common subtypes include peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), extranodal NK/T-cell lymphoma nasal type (NK/T), and T-lymphoblastic lymphoma (T-LBL). Hematopoietic stem cell transplantation (HSCT) offers a potential strategy to improve outcomes, however, data on TCL prognosis following HSCT in middle-income countries, remain limited. Methods: We conducted a retrospective analysis of patients with TCL who underwent HSCT at a national referral center in Mexico from 2008 to 2024. Descriptive statistics and comparative analysis were performed. Survival analysis was conducted using Kaplan-Meier curves with comparisons by log-rank test. Results: A total of 40 patients were included, 55% were female, with a mean age of 36 ± 13 years. Most had ECOG 0–1 (82.5%), and 60% B symptoms. TCL subtypes included: NK/T (52.5%; 21/40), ALCL (22.5%, 9/40; ALK-positive: 4/9, ALK-negative: 5/9), PTCL-NOS (17.5%; 7/40), T-LBL (5%; 2/40), and AITL (2.5%; 1/40). Inmunohistochemical markers included: CD30 (37.5%), EBER (88.2% in NK/T), and Ki-67 median of 75% (IQR: 52-80). Advanced-stage disease (stage III-IV) was present in 60%. Median number of extranodal sites was 1 (IQR 0–2), and bone marrow and CNS involvement was identified in 7.5% and 5%, respectively. Risk stratification varied by TCLs subtype and score used. For NK/T-cell lymphomas (n=21), 76.2% were low-risk by IPI, 33% low-intermediate risk by PIT, 45% low-risk by PINK; and 44% by PINK-E. High-risk was found in 9.5% by IPI, 22.2% by PIT, 50% by CA system, 40% by PINK, and 27.8% by PINK-E. In PTCL-NOS (n=7), 71.4% were low-intermediate risk by IPI. According to PIT score, 42.9% were low-intermediate risk and 28.6% low-risk. Among ALCL (n=9), 66.7% were low-intermediate risk by IPI and 80% high-intermediate risk by PIT. First-line therapy was anthracycline-based in 67.5%, L-asparaginase-based in 25%, and other regimens in 7.5%. Four (10%) patients received brentuximab. Radiotherapy was administered in 72.5%. CR prior to HSCT was achieved in 95%, with a median of 2 prior treatment lines. HSCT was performed as consolidation in CR1 in 42.5% and in R/R cases in 57.5%. Median time from diagnosis to HSCT was 22 months (IQR 15-29). Autologous HSCT was conducted in 87.5% (35/40), and allogeneic in 12.5% (5/40); mostly HLA-matched sibling donor in 80% (4/5) and haploidentical in 20% (1/5). Myeloablative conditioning was used in 92.5%, primarily PEAM in autologous, and fludarabine/busulfan-based regimens in allogenic settings. Post-HSCT PET-CT at day +100 confirmed CR in 90%. Post-transplant complications in allogenic recipients were: infections in 100% (5/5), and GVHD in 60% (3/5). No transplant-related mortality was identified. During follow-up, 15% (6/40) experienced disease progression and 7.5% (3/40) died. Median overall survival (OS) was 60 months (IQR 33–103), progression-free survival (PFS) was 28 months (IQR 28–102), and 19 months (IQR 7–72) from the time of HSCT. Two-year OS rate was 100% in all groups. No significant outcome differences were found between patients who underwent HSCT as consolidation therapy and those in the R/R setting. However, the risk of disease progression after HSCT was twice as high in the R/R group. At five years, OS and PFS were as follows: for PTCL-NOS, 60 months (IQR 33-60) and 60 months (IQR 23-60), respectively; for ALCL, 60 months (IQR 31-60) and 48 months (IQR 29-60); and for NK/T-cell lymphoma, 44 months (IQR 27-60) and 43 months (IQR 26-60). When analyzed from the time of HSCT, the 5-year PFS was: 60 months (IQR 12-60) for PTCL-NOS, 60 months for AITL, 27 months (IQR 16-60) for ALCL, 10 months (IQR 5-60) for NK/T, and 16 months for T-LBL. Conclusion: HSCT proved to be a viable therapeutic option, particularly in advanced-stage disease, challenging the historically poor outcomes associated with TCL. HSCT was successfully performed as consolidation therapy and in R/R cases, resulting in improved outcomes. The increased risk of progression in R/R group reinforces the value of HSCT as consolidation in CR1. Our findings also provide a real-world insight into the implementation of EBMT 2025 guidelines in Latin American context, emphasizing the feasibility and potential impact of HSCT in TCL.