Prognostic Impact of Organ Involvement in Aggressive Adult T-Cell Leukemia/Lymphoma

Overview

This study identifies lung, liver, and central nervous system (CNS) involvement as key risk organs associated with poor overall survival (OS) in aggressive adult T-cell leukemia/lymphoma (ATL). A new risk organ index incorporating these sites further stratifies prognosis beyond existing clinical staging.

Background

Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoma linked to HTLV-1 infection and carries a poor prognosis, especially in its acute, lymphoma, and unfavorable chronic types. Most aggressive ATL cases present with advanced clinical stage (≥stage III), limiting the utility of current prognostic indices that emphasize clinical stage. Extranodal organ involvement is common in ATL, but its detailed impact on prognosis has not been fully elucidated. This study aimed to clarify the prognostic significance of specific organ involvement to improve risk stratification in aggressive ATL.

Data Highlights

Median OS by number of involved organs: ≤3 lesions - not reached; 4–5 lesions - 34.8 months; ≥6 lesions - 10.0 months. Two-year OS: 81.9%, 67.8%, and 10.1%, respectively.

Key Findings

• Among 140 aggressive ATL patients, 99% were clinical stage IV, with a median OS of 20.8 months.
• Lung, liver, and CNS involvement were independently associated with significantly worse OS.
• A risk organ index was created assigning 2 points for CNS involvement and 1 point each for lung and liver involvement, effectively stratifying patients into distinct prognostic groups.
• Patients with involvement of ≥6 organs had markedly poorer survival compared to those with fewer involved sites.
• Risk organ involvement remained the only significant prognostic factor in multivariate analysis including established clinical and laboratory parameters.
• Patients with CNS and lung involvement had poorer performance status and were less likely to receive allogeneic hematopoietic cell transplantation.

Clinical Implications

Assessment of lung, liver, and CNS involvement should be integrated into routine evaluation of aggressive ATL to refine prognostic stratification. The proposed risk organ index may guide treatment decisions, including candidacy for intensive therapies such as allo-HCT. Recognizing patients with multiple organ involvement can identify those at highest risk who may benefit from novel therapeutic approaches.

Conclusion

Organ involvement, particularly of the lung, liver, and CNS, is a critical determinant of prognosis in aggressive ATL. Incorporating risk organ criteria into prognostic models enhances risk stratification beyond clinical stage alone.

References

1. Katsuya et al. 2024 -- Prognostic Significance of Organ Involvement in Aggressive Adult T-Cell Leukemia/Lymphoma