Clinicopathologic Features and Survival Determinants of Hepatosplenic T-Cell Lymphoma: A Pooled Patient-Level Dataset Analysis.
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Hepatosplenic T-cell lymphoma (HSTCL) is an ultra-rare, aggressive T-cell neoplasm for which evidence regarding prognosis and optimal therapy remains limited. We conducted a retrospective pooled patient-level analysis of 529 patients from 198 sources. The median age was 32 years, with 71.7% male. Hepatosplenomegaly and bone marrow involvement were present in 99.7% and 91.8% of evaluable patients, respectively. Among 436 patients with evaluable overall survival (OS), the median OS was 12.0 months, and the median progression-free survival was 5.0 months. Multivariable analysis demonstrated that hemoglobin less than 8 g/dL (HR 3.36, 95% CI 1.61-7.00; p = 0.0012) and underlying immunosuppression (HR 3.00, 95% CI 1.77-5.06; p < 0.0001) independently predicted inferior OS, while time-dependent stem cell transplantation (SCT) was associated with improved survival (HR 0.31, 95% CI 0.15-0.65; p = 0.0021). A provisional two-point score incorporating severe anemia and immunosuppression stratified patients into low-, intermediate-, and high-risk groups, with median OS of 26, 5, and 3 months, respectively (log-rank p < 0.0001; C-index 0.706). Platinum-containing first-line regimens were associated with lower mortality compared to CHOP-like therapy (HR 0.43, 95% CI 0.25-0.75; p = 0.003). The SCT survival association was consistent across complementary analyses. Nonresponsive, stable, or progressive disease at transplantation predicted inferior post-transplant survival compared to complete response (HR 2.84, 95% CI 1.32-6.10; p = 0.007). These findings identify severe anemia and immunosuppression as adverse prognostic features, support non-CHOP platinum-based induction and early SCT evaluation after disease control. However, because this is a retrospective pooled design, the treatment associations and the provisional prognostic score still require external validation.