T-cell prolymphocytic leukemia: A review of induction therapies.

Abstract

e18617 Background: T cell prolymphocytic leukemia (T-PLL) is an aggressive neoplasm composed of mature T cells, with a median survival of under 1 year. Hematopoietic cell transplantation (HCT) is curative, but requires pre-transplant remission. While intravenous (IV) alemtuzumab has emerged as the primary induction therapy, combination therapies including pentostatin, fludarabine, cyclophosphamide, and mitoxantrone (FMC), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remain under-evaluated. This study aims to analyze overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and major adverse effects (AEs) across these regimens. Methods: A systematic search of PubMed and Web of Science using the terms: "Leukemia, Prolymphocytic, T-Cell" OR "T-cell prolymphocytic leukemia" AND "Alemtuzumab" OR "Campath." No date restrictions were applied. The search identified 253 documents. Titles and abstracts were screened for relevance. English language studies on chemotherapeutic interventions in T-cell prolymphocytic leukemia were included. Articles focusing on stem cell transplantation, opinion pieces, or consensus statements without transparent methodology were excluded. Eight articles were selected for qualitative analysis. Results: Alemtuzumab-based therapy significantly improved survival over historical regimens. IV administration was superior to subcutaneous (SubQ) for OS and PFS. Sequential FMC followed by alemtuzumab (FMC-A) produced similar survival outcomes but was associated with a high incidence of infectious complications. The addition of pentostatin to alemtuzumab achieved ORRs of 70–80%, although it increased cumulative myelosuppression. Historical regimens like CHOP were associated with lower ORR, OS, PFS, and rapid relapse. Conclusions: IV alemtuzumab monotherapy is a superior induction agent compared to SubQ administration and prior cytotoxic regimens. Although FMC-A achieves high response rates, it is associated with an increased risk of grade 3–4 AEs, particularly cytomegalovirus morbidity and neutropenia. As long-term survival depends on successful HCT, rapid remission is preferred to facilitate transplant bridging. Further efforts to improve outcomes in T-PLL should incorporate data on complete remission rates and efficacy of novel agents like JAK/STAT or BCL-2 inhibitors. Efficacy and safety summary of targeted vs. cytotoxic induction in T-PLL. Regimen (Key Refs) Est. N ORR (%) Median OS (mo) Median PFS (mo) Adverse Effects Alemtuzumab IV (1, 2) 210 76–92 15.0–21.6 10.0–11.2 CMV reactivation, minor infusion reactions Alemtuzumab SubQ (1, 3) 16 33 9.6 4.7 Primary refractory disease Sequential FMC-A (4, 5) 41 92 17.1 11.9 91% CMV reactivation, neutropenia Alemtuzumab+ Pentostatin (6) 50 70–80 10.0–13.0 7.0 Cumulative myelosuppression CHOP / Purine Analogs (7, 8) 150 20–40 7.0–13.0 < 6.0 Hematologic toxicity, rapid relapse