Comparative Analysis of Treatment Outcomes in T-Cell Acute Lymphoblastic Leukemia and T-Cell Lymphoblastic Lymphoma: Implications for Allogeneic Hematopoietic Stem Cell Transplantation

Introduction

T-cell lymphoblastic leukemia/lymphoma (T-ALL/LBL) represents a spectrum of aggressive neoplasms derived from precursor T-cells. While the World Health Organization classifies T-ALL and T-LBL as a single entity, their clinical presentations and treatment approaches often differ in practice. The optimal role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial, particularly for T-LBL. This study aimed to compare outcomes between T-ALL and T-LBL and identify patients who would benefit most from allo-HSCT.

Materials and Methods

We retrospectively analyzed 148 adult patients (≥18 years) diagnosed with T-LBL (n=67, 45.3%) or T-ALL (n=81, 54.7%) between November 2009 and December 2022 at seven hospitals in South Korea. Patients were followed until June 2024. T-ALL was diagnosed by bone marrow biopsy showing >20% blasts, while T-LBL was initially diagnosed by biopsy of nodal or extranodal sites, with or without bone marrow involvement. Patients with T-LBL received alternating cycles of hyper-CVAD and high-dose methotrexate/cytarabine, with consideration for autologous HSCT in first complete remission (CR1). T-ALL patients were treated with modified hyper-CVAD alternating with high-dose cytarabine and mitoxantrone, with frontline allo-HSCT recommended for all patients in CR1. Conditioning regimens for allo-HSCT included myeloablative and reduced-intensity protocols. Overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse, and non-relapse mortality were analyzed. Univariate and multivariate analyses were performed using Cox proportional hazards models, and risk stratification was conducted using survival decision trees.

Results

The median follow-up for survivors was 5 years. Five-year OS rates for T-LBL and T-ALL were 43.5% and 52.8%, respectively (p=0.111). PFS was significantly lower in the T-LBL group (p<0.001). Five-year OS rates for allo-HSCT, autologous HSCT, and chemotherapy-only groups were 62.8%, 62.4%, and 13%, respectively (p<0.001). Multivariate analysis identified ≥2 extranodal sites (HR 2.1, 95% CI 1.3-3.4, p=0.002), mass >6 cm (HR 1.8, 95% CI 1.1-2.9, p=0.018), axial bone involvement (HR 1.7, 95% CI 1.0-2.8, p=0.04), and non-CR status after chemotherapy (HR 3.2, 95% CI 2.0-5.1, p<0.001) as independent risk factors for poor OS. In the allo-HSCT cohort, there were no significant differences in OS, PFS, cumulative incidence of relapse, or non-relapse mortality between T-LBL and T-ALL groups. Pre-transplant disease status strongly influenced outcomes, with only the CR group demonstrating long-term survival.

Conclusion

Our findings suggest that patients with T-LBL who have ≥2 extranodal sites or large tumor masses should be considered for upfront allo-HSCT, similar to high-risk T-ALL patients. The efficacy of allo-HSCT in both T-ALL and T-LBL, when performed in CR, supports a unified approach to transplantation for these related entities. The superior outcomes observed with both allo-HSCT and auto-HSCT compared to chemotherapy alone underscore the value of consolidative transplantation in this high-risk population. However, the critical importance of achieving CR before transplantation emphasizes the need for effective induction and salvage strategies. Prospective studies are needed to validate these findings and further refine risk-adapted treatment strategies for T-ALL/LBL, particularly regarding the optimal timing and patient selection for allo-HSCT.

No relevant conflicts of interest to declare.