Disaggregating aggressive ATLL: A retrospective Study focused on the lymphomatous variant in Latin America

Abstract Background: The different subtypes of ATLL, as per the Shimoyama classification, are consistently described as distinct diseases in terms of their clinical features, outcomes, and even distinctive molecular patterns. However, it is common to analyze the aggressive ATLL types (acute and lymphoma type) together, which can obscure the unique clinical and biological characteristics of each subtype thereby making it more challenging to understand this complex and difficult-to-treat disease. The objective of this study is to describe a cohort of patients with the lymphomatous type of ATLL in Latin America. Methods: We conducted a cohort study among patients ≥18 years with newly diagnosed ATLL and selected all lymphoma type from T-cell Brazil Project (TCBP, Ambispective, Clinicaltrials.gov ID= NCT03207789, 2015-2025, n= 51) and the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL, Retrospective, 2000-2023, n= 126). Clinical and biological data at diagnosis were collected, along with information on treatment, response, and follow-up. The Kaplan-Meier method was used to estimate survival, while the Log-Rank test was applied to compare the curves. Additionally, Cox regression models were used to identify prognostic factors for OS and EFS, with a significance level of 5%. Results: This analysis included a total of 177 cases, comprising 100 from Peru, 51 from Brazil, 13 from Chile, 7 from Argentina, and 6 from Colombia. The median age was 54 years (20-95), with 50.6% male, 83% having advanced disease (Ann Arbor stage III-IV), 44% with extra-nodal involvement, 61% having an IPI score of 3-5, and 59% having a PIT score of 2-4. The treatment was likely curative in almost 97% (72% chemotherapy (CT) alone, 18% CT + AZT and INF, 7% AZT + INF). CHOP-like was the most used (44% CHOP and 29% CHOEP). 28% had a complete response after 1st line therapy and 39% no response/progression. Only 5 (3%) received transplantation as consolidation, and 68% had progression/relapse. The median follow-up duration of the survivors was 14 months (1-182). 24-month OS was 28% and 18% for EFS. The final Cox model for OS was median age ≥ 54y (HR 2.35 95%CI 1.55-3.57, p< 0.0001), ECOG ≥2 (HR 1.90 95%CI 1.22-2.97, p=0.005), higher LDH (HR 2.77, 95%CI 1.50-5.10, p=0-.001) and B symptoms (HR 2.65, 95%CI 1.61-4.37, p<0.0001), and for EFS the final model was compound with the same prognosis factors.Conclusion: To our knowledge, this study represents the largest cohort of the ATLL lymphoma subtype in Latin America and suggests that OS and EFS for this malignancy remains poor, primarily due to advanced stage at diagnosis, high-risk clinical features, and limited access to adequate therapy. These findings underscore the need for a richer understanding of the condition to enable appropriate risk stratification and guide clinical trials exploring newer therapeutic approaches.