Comparable outcomes after autologous hematopoietic cell transplantation in T-cell lymphoma regardless of pre-transplant response: A key finding in resource-limited countries.

Abstract Introduction. T-cell lymphomas represent about 10% of non-Hodgkin lymphomas (NHL), are a rare type and the incidence is variable around the world. These are tumors of mature T-lymphocytes with generally poor outcomes, with registers a 5-year survival rate of 30% to 40%. Over time, we have been learning and understanding the biology of the origin cell of these lymphomas, which has led to new classifications, opening opportunities for specific treatments. In resource-limited countries are still CHOP-like regimens the first line treatment for this group of patients and consolidation with Autologous hematopoietic cell transplantation (AHCT) after the first line may provide a survival benefit, demonstrating a 3-year overall survival (OS) of 51% and progression-free survival (PFS) of 44%. In limited resources countries, AHCT is a very important tool due to its extensive availability, in contrast with target treatment, highlighting the need to know and improve the results of the available therapies in our population. Methods. Study type: Retrospective, analytical, multi-institutional study including all adult transplantation centers in Uruguay. Database: An Ad-HOC database was developed, including patients' data from 2000 to 2024 diagnosed with T-cell NHL (T-NHL). Primary aim: To describe PFS and OS in the subgroup of T-NHL patients who underwent AHCT. Exclusion criteria: Patents diagnosed with cutaneous, hepatosplenic, enteropathy-associated or lymphoblastic subtypes of T-NHL. Results. A total of 93 patients underwent AHCT across the three adult transplantation centers in Uruguay. Patients were stratified by disease according to distinct clinical profiles (see exclusion criteria). Eighty patients were eligible for analysis, encompassing Anaplastic, Angioimmunoblastic and not otherwise specified (T-NOS) subtypes of T-NHL. Forty-nine patients (61.3%) were man; the median age was 51 years (range 24 – 72y), 27 patients (33.8%) were aged 60 years or older. Regarding the subtypes of T-NHL, 40 patients (50.0%) had T-NOS, 27 patients (33.7%) anaplastic, (ALK- 23 patients), and 13 patients (16.32%) angioimmunoblastic. Fifty-three patients (66.4%) classified as an Ann Arbor stage III or IV at diagnosis. The frontline therapy was CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) in 27 patients (33.8%) and 29 patients (36.3%) received additional Etoposide (CHOEP). The median lines of treatment before AHCT was 1 (range 1-4), thirty patients (37.5%) had received 2 or more lines before AHCT. Positron emission tomography (PET) evaluation was performed in 31 patients (38.8%). Regardless of imaging modality, PET or computed tomography (CT), complete response (CR) prior to transplant was achieved in 42 patients (53.2%), and partial response (PR) in 33 patients (41.8%). After AHCT a further deepening of response was observed in 23 patients (28.8%). We conducted logistic regression analysis to identify factors associated with relapse. Age ≥60 years (OR 2.21 IC 95% 0.86 – 5.70 p=0.09), ≥2 prior treatments lines (OR 2.44 IC 95% 0.97 – 6.18 p= 0.058) and failure to achieve metabolic CR prior AHCT (OR 1.40 IC 95% 0.48 – 4.17 p=0.53), showed trends toward increased risk but did not reach statistical significance. Survival analysis similarly demonstrated no significant differences for age ≥60 years (OR 1.41 IC 95% 0.56 - 3.60 p=0.46), ≥2 prior lines (OR 1.31 IC 95% 0.53 – 3.27 p= 0.56) or lack of metabolic CR (OR 2.95 IC 95% 0.87 – 10.0 p=0.083). Among patients achieving CR after AHCT, the median duration of response (DOR) was 104 months. Five years PFS was 59% and OS was 62%. PFS at 5 years according to subtype was 69% for anaplastic, 60% for T-NOS and 34% for angioimmunoblastic (p = 0.060). Subtype specific OS rates at 5 years were 79%, 53% and 56% for anaplastic, T-NOS and angioimmunoblastic, respectively (p = 0. 048). Conclusion. In countries with limited resources, conventional chemotherapy followed by AHCT remains a feasible and affordable consolidation strategy for patients with T-NHL. In this national cohort (AHCT candidates), both PFS and OS appear more favorable compared to previous international reports. Data on T-NHL treated with AHCT in Latin America is notably scarce, highlighting an unmet need to improve outcomes in setting where access to novel agents is not commonly available. Nevertheless, our finding suggests that AHCT continues to be a valuable therapeutic tool, even though CR is not achieved before transplantation.