Adult T-cell leukemia/lymphoma (ATLL) is a mature, peripheral T-cell neoplasm caused by HTLV-1 and its lifetime risk is estimated as 4-7% among HTLV-1 carriers. Acute and lymphoma subtypes are highly aggressive diseases, characterized by shorter survival rates and a high risk of central nervous system involvement (iCNS) compared to other peripheral T-cell lymphomas. Currently, the treatment of ATLL remains a challenging. Our recent study on PTCL epidemiology and outcomes in Latin America (Thais et al. 2023 ASH Meeting) highlighted ATLL (18%) as the second most frequent subtype of PTCL, likely influenced by our distinct viral epidemiology.

It is to assess the prevalence, clinical features, risk factors, and outcomes of iCNS in ATLL in Latin America.

Patients (pts) aged ≥18 years with newly diagnosed ATLL from GELL (n = 208, 2000-2023, retrospective) and TCBP (n = 83, 2015-2022, ambispective). Overall survival (OS) and progression free survival (PFS) were our endpoints. REDcap Platform (by Vanderbilt) was used to collect and store data, whereas for statistical analysis IBM-SPSS v.24. This trial is registered at Clinical trials (NCT03207789).

It was enrolled 291 pts, the prevalence of iCNS in ATLL was 7.9% (23/291), considering only aggressive forms (acute 40% and 60% lymphomatous). Pts'characteristics were similar between those without and with iCNS. There was a high frequency of advanced stage (90% vs 82%); ECOG ≥ 2 (45% vs 43%); B symptoms (74% vs 56%); elevated LDH (84% vs 78%); and IPI ≥3 (82% vs 65%) in the iCNS group. Treatment was heterogeneous including: IFN+AZT (74%) for acute subtypes, and CHOP (52%), CHOEP (26%) and EPOCH (2%), for lymphoma subtypes. Less than 30% of both groups achieved complete response at end of first treatment. Two clinical features were identified as possibly associated to iCNS: median age at diagnosis (55 [20-95] vs 44 [23-65]; p < 0.0001) and extra nodal involvement ≥ 2 (32% vs 65%, p = 0.005). The entire cohort of ATLL had 60- month OS and PFS of 16% [95% CI: 12-20%] and 9% [95% CI: 5-13%]; with median time of OS and PFS of 7 months (6-9) and 5 months (4-6). iCNS did not have an impact on survival outcomes (60 months OS 14% iCNS (n = 23) vs 16% no iCNS (n = 254), p = 0.91; PFS 12% vs 9% no iCNS, p = 0.61;) despite being a devastating complication. Outcomes in pts with lymphoma subtypes were slightly better than acute (60 months OS 19% vs 10%, p < 0.0001; PFS 12% vs 5%, p < 0.0001, respectively).

Unlike other lymphoma subtypes, iCNS in ATLL does not appear to significantly impact outcomes. This paradoxical finding underscores the complexity of ATLL and may reflect the limitations of existing treatment options and the absence of standardized therapeutic protocols for this aggressive malignancy. The lack of significant survival difference, despite the severity of iCNS, points to an urgent need for innovative therapies and more effective treatment strategies. Our analysis identified median age at diagnosis and extranodal involvement as potential risk factors for iCNS, suggesting avenues for future prospective studies to further elucidate their role in disease progression. Given the high prevalence of ATLL in Latin America, there is a unique opportunity to advance our understanding of this disease through region-specific research. Collaborative efforts in this region could pave the way for breakthroughs in the management of ATLL and potentially offer insights applicable on a global scale.