Characteristics, Outcomes and Treatment of Patients with T-Cell Prolymphocytic Leukemia (T-PLL) - Single-Center Experience

Abstract Background: T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive mature T-cell lymphoid leukemia. T-PLL is diagnosed based on characteristic immunophenotype, cytogenetic, and molecular aberrations (including members of the JAK-STAT signaling pathway) which may explain its aggressive clinical course. Cytogenetic features include chromosome (chr) 14 aberrations, accompanied by gene rearrangement involving proto-oncogenes TCL1 or MTCP1. In this analysis, we report our single-institution experience with T-PLL over the last 25 years. Methods: We reviewed the clinico-pathologic records of 101 consecutive patients (pts) with T-PLL, who presented to our institution between 1990 and 2015. The survival (OS) of pts was calculated from the date of initial presentation to the date of last follow up. Kaplan-Meier product limit method was used to estimate the median OS. Results: Median age of pts was 64 years (range 35-87 years). Eighteen pts (18%) presented with a performance status of 2 or higher. Lymphadenopathy, splenomegaly, skin lesions, hepatomegaly and pleural effusion were seen in 58%, 37%, 30%, 8%, and 7% of pts, respectively. Complex karyotype and aberrations in chr 14 were seen in 54 (63%) and 42 (49%) pts, respectively. TCL1 expression by immunohistochemistry was performed in 29 pts. The overexpression of TCL1 was detected in 23/29 pts (79%). Among untreated pts, 18/47 (38%) had a chr abnormality involving TCL-1. At initial presentation to our center, 59 pts (58%) were untreated and 42 pts (42%) had relapsed/refractory disease with a median of 2 prior treatments (range 1-6). Seventy-one pts (70%) were treated at our institution. Median overall OS from diagnosis in all pts was 21.7 mos (Range 1.5-107.7 mos). Median OS was longer in untreated pts than in pts with relapsed/refractory disease (27 mos vs. 17 mos; P=0.08). In a multivariate analysis for assessing the prognostic factors for OS in 43 untreated pts in whom all variables were available, we found that the presence of a pleural effusion HR (95% CI) 5.21 (1-27; P Conclusions: In this retrospective analysis, we have observed that outcomes in T-PLL remain poor. We have shown that alemtuzumab has some therapeutic activity in pts with T-PLL but durable remissions are uncommon. Rarity of this disease limits the conduct of large scale clinical trials; hence multicenter collaborative effort is required to conduct prospective studies. In pts who achieve a CR, consolidation treatment with SCT did not improve survival in our series. Studies to further define the genomic imbalances in pts with T-PLL and identify potential therapeutic targets and pathways providing drug resistance in T-PLL are underway. Download : Download high-res image (100KB) Download : Download full-size image Download : Download high-res image (69KB) Download : Download full-size image Disclosures O'Brien: Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Wierda: Acerta: Research Funding; Novartis: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Genentech: Research Funding. Jain: Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Novimmune: Consultancy, Honoraria; Abbvie: Research Funding; Servier: Consultancy, Honoraria; Seattle Genetics: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Infinity: Research Funding; Incyte: Research Funding; BMS: Research Funding. Thompson: Pharmacyclics: Consultancy, Honoraria. Kantarjian: BMS, Pfizer, Amgen, Novartis: Research Funding.