Abstract 5765: Epidemiology and clinicopathology prognostic factors of T-cell prolymphocytic leukemia: Analysis and met-analysis of updated pooled databases
Authors: Haddad Philip A. , Gallagher Kevin , Hammoud Dalia 
Published: September 2020

Abstract
TPLL is a rare and aggressive T-cell lymphoid malignancy. It typically presents with leukocytosis, hepatosplenomegaly, lymphadenopathy, and skin involvement. The post-thymic malignant lymphocytes often express CD2, CD3, CD4, CD5, and occasionally CD8. CD52 is also frequently and densely expressed and serves as a therapeutic target for the monoclonal antibody, Alemtuzumab. Inv(14) and chromosome 14 translocations (tchr14) are the most frequent cytogenetic abnormalities contributing to the overexpression of the TCL-1 gene product. This analysis was conducted to update and expand our existing knowledge of this rare disease. To study the demographic characteristics, cytogenetic and molecular signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 91 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathology factors on survival. A search of online databases identified all available comparative studies of Alemtuzumab in TPLL to conduct a meta-analysis using an inverse variance method with a fixed-effects model. The median age was 65 (27-89) years, with a peak incidence between ages 71 and 81. Males were 1.8 times more afflicted than females. The median overall survival of the whole group was 21 months. Sex did not impact the overall survival of the group. When compared to supportive care, chemotherapy significantly improved survival (HR:0.29, p=0.0016). Allogeneic stem cell transplant did not confer any survival advantage. Moreover, the presence of SAMHD1 and JAK-STAT mutations did not affect survival. The median survival of inv(14), tchr14, and TCL-1 expression were 29, 12, and 11 months respectively. When compared to tchr14 and TCL-1 expression combined, inv(14) seems to have a borderline significant survival advantage (HR:0.52, p=0.06). Patients who were treated with Alemtuzumab had higher median survival, though not significant, compared to those who did not (29 vs 12 months, p=0.6). To study further the effect of Alemtuzumab on TPLL survivorship, we conducted a meta-analysis of four retrospective comparative series with a total of 144 patients including ours. Alemtuzumab was found to be significantly associated with a survival benefit in patients with TPLL (HR 0.54, p=0.001). This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with TPLL. It identifies the potential prognostic impact of inv(14), tchr14, and TCL-1 on survival. Furthermore, it confirms the survival advantage conferred by Alemtuzumab in TPLL.
Citation Format: Philip A. Haddad, Kevin Gallagher, Dalia Hammoud. Epidemiology and clinicopathology prognostic factors of T-cell prolymphocytic leukemia: Analysis and met-analysis of updated pooled databases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5765.