Relapsed/Refractory ETP-ALL Successfully Treated With Venetoclax and Nelarabine as a Bridge to Allogeneic Stem Cell Transplant

摘要

T-lymphoblastic leukemia/ lymphoma (T-ALL/LBL) is a malignant neoplasm of immature T-cells with characteristic immunophenotypic subtypes that correspond to T-cell maturation stages. Early T-cell precursor lymphoblastic leukemia (ETP-ALL) is one such subtype, which is derived from thymic cells at the early T-cell precursor differentiation stage and make up 5% to 16% of T-ALL cases. ETP-ALL cells are derived from hematopoietic stem cells that have recently migrated to the thymus, and retain multilineage pluripotency. They display reduced expression of T cell antigens; typically CD1a(−), CD5(−/dim) and CD8(−), and display aberrant expression of stem cell or myeloid antigens. Congruently, the genetic mutations seen in ETP-ALL are similar to those found in poorly differentiated myeloid neoplasms and mixed phenotype T/myeloid acute leukemia. Historically, ETP-ALL has a poor prognosis with standard chemotherapy but similar outcomes to T-ALL are reported when treated with contemporary protocols. Recent research has described how ETP-ALL both expresses and is dependent on BCL2, and hence how antagonists such as ABT-199 (venetoclax) may offer a potential therapeutic benefit. We report a patient with relapsed/ refractory ETP-ALL, with defined molecular mutations on next generation sequencing (NGS) at the time of relapse, who had an excellent response to venetoclax in combination with nelarabine allowing progression to allogeneic stem cell transplant. We propose this novel treatment strategy is worth further investigation, especially in light of adverse outcomes seen in this disease.