Background:

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and highly aggressive peripheral T-cell lymphoma characterized by extranodal infiltration of the liver, spleen, and bone marrow, with minimal lymphadenopathy. Predominantly affecting adolescents and young adults, HSTCL is frequently associated with underlying immunosuppression. The clinical course is often fulminant, with limited responses to conventional chemotherapeutic regimens and a poor survival. Due to its rarity, much of the current understanding of HSTCL derives from case reports and small retrospective series, leaving significant gaps in knowledge regarding prognostic factors and optimal management strategies. Comprehensive analyses utilizing real-world data are needed to elucidate the clinicopathologic determinants that most strongly influence survival outcomes in this challenging disease.

Methods:

To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled a pooled database of real-world cases that satisfy the diagnostic criteria for HSTCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS).

Results:

A total of 449 patients with confirmed HSTCL were identified, with a median age of 31 years and peak incidence between ages 16 and 24. There was a marked male predominance (M:F ratio 3:1 overall and in γδ subtype; 6:1 in immunosuppressed; 1.5:1 in αβ subtype). Median overall OS was 11 months. Median time from symptom onset to diagnosis was 2 months. Among patients with prior immunosuppression, the median duration of therapy and interval from immunosuppression to HSTCL diagnosis were both 5 years. Sex, age, white blood cell or platelet counts, LDH, i7/r7, CD56+, skin, hepatosplenic or lymph node involvement, and prior use of TNFα inhibitors or steroids did not significantly impact OS. Factors associated with worse OS included hemoglobin <8 g/dL, prior immunosuppression, use of chemotherapeutic agents (including purine analogues), and underlying inflammatory bowel disease, organ transplant, and malignancy. Constitutional symptoms and bone marrow involvement had numerically worse OS but did not reach statistical significance. TCR-rearrangement also influenced OS (null > αβ = γδ > biclonal, p=0.02). Compared to no treatment, splenectomy (S), chemotherapy (CT), CT+S, stem cell transplant (SCT), and SCT+S were all associated with improved median OS (1, 4, 7, 18, 44, and 30 months, respectively; p<0.0001). No significant OS difference was observed between autologous and allogeneic SCT, although survival curves plateaued with allogeneic SCT. Quality of response to therapy (p<0.0001) and type of response at the time of SCT (p=0.0002) correlated with improved OS, with CR>PR>NR. Platinum-based first-line regimens outperformed etoposide-containing, asparaginase-containing, and intensive regimens, which in turn were superior to CHOP in OS.

Conclusion:

This large real-world analysis identifies key clinical and treatment-related factors impacting survival in HSTCL. Underlying immunosuppression, severe anemia, and poor response to therapy are associated with worse outcomes, while splenectomy, first-line platinum-containing regimens, and stem cell transplantation confer significant survival benefits. These findings underscore the need for early aggressive, multimodal management to improve prognosis in this challenging disease.

This content is only available as a PDF.
2025
Sign in via your Institution