Background Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive mature T-cell neoplasm associated with chronic HTLV-1 infection. It is characterized by heterogeneity in clinical presentation and poor prognosis, particularly in non-endemic regions such as the United States (U.S.), where patients (pts) are predominantly of Afro-Caribbean and Hispanic descent. Despite decades since its recognition, there have been limited therapeutic advances. Most pts experience early relapse or primary refractory disease, and outcomes after conventional chemotherapy remain poor. Real-world data on treatment patterns and survival are scarce.

Method We conducted a retrospective single-center study of 51 pts with confirmed ATLL treated at Moffitt Cancer Center from 2006 to 2024. Pts were identified using ICD codes and serum and/or tissue HTLV-1 positivity with histologic confirmation by expert hematopathologist review. Demographic, clinical, and treatment data, including first-line therapy, salvage treatments, and allogeneic hematopoietic stem cell transplant (alloHCT) status, were extracted from medical records. ATLL subtypes were defined per 2017 WHO criteria. Kaplan-Meier estimates were used to analyze survival, stratified by subtype.

Results Among the 51 pts included, subtypes were acute (49%), lymphomatous (47%), and chronic (4%). The median age at diagnosis was 54 years (range, 31–78); 51% were male. Most pts were Black (78%), and most originated from the Caribbean (43%) or the U.S. (20%). Fourty-seven percent of pts presented with relapsed/refractory disease. Notably, 14% of pts were initially diagnosed as PTCL-NOS or CTCL and no HTLV1 testing was performed at the center of referral.

High-risk clinical features were common, including elevated LDH >2× ULN (67%), hypercalcemia (46%), leukocytosis in acute ATLL (median 31 × 10⁹/L), and hypoalbuminemia (12%). Seven pts (14%) had chronic subtype before transforming into aggressive subtypes.

Among 46 evaluable pts with aggressive subtypes (after excluding three lost to follow-up), 41 died. Median overall survival (OS) was 10.3 months (95% CI: 5.3–15). The median OS was 9.5 months for acute ATLL (95% CI: 3.5–19.8) and 10.3 months for lymphoma ATLL (95% CI: 5.3–15), with no statistically significant difference (HR 0.69, 95% CI: 0.37–1.27).

Among acute ATLL pts (n=25), initial therapy included CHOP or CHOEP (40%), hyperCVAD (28%), and Zidovudine + interferon a (AZT+IFN) (20%). Among pts with evaluable response, ORR for anthracycline-based combination therapy was 20% (3 CRs out of 15 pts). Those treated with AZT+IFN upfront had disproportionately higher survival beyond two years, especially when followed by mogamulizumab or transplant. Mogamulizumab was used in 36% of acute pts, most commonly in the relapsed setting. Four pts (16%) were consolidated with AlloHCT after first response, and 3 remain alive without disease after follow-up of 2 years, 12 years, and 17 years, respectively.

Among lymphomatous subtypes pts (n=24), the majority received CHOP-based regimens initially (79%), followed by salvage with ICE, pralatrexate, or romidepsin. Among pts with evaluable response, ORR for anthracycline-based combination therapy was 65% (9 CRs, 4 PRs out of 20 pts). Four pts (17%) were consolidated with AlloHCT, but none led to durable remission: three pts relapsed within 3 months, and one relapsed at 2 years. Overall, responses were short-lived, and survival was poor, with only two pts surviving beyond two years.

Conclusion In this 20-year single-institution study, ATLL demonstrated extremely poor survival outcomes in a U.S.-based population. OS was under one year across aggressive subtypes, and conventional chemotherapy yielded limited efficacy. A small number of long-term survivors were observed in acute ATLL with limited tumor burden in the lymph node involvement, associated with early use of AZT+IFN, followed by mogamulizumab, or AlloHCT. A change in initial diagnosis occurred in 14% of pts, highlighting the need for HTLV-1 testing in pts with nodal and cutaneous T-cell NHL. Unfortunately, we currently lack highly effective frontline treatment options, which makes consolidative strategies such as transplantation difficult to execute. These findings underscore the urgent need for earlier recognition, subtype-adapted therapy, and suggest the incorporation of antiviral and immune-based strategies to improve ATLL outcomes.

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2025
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