Although the current overall 5-year survival rate for acute lymphoblastic leukemia (ALL) is more than 85%, patients with some subsets of ALL continue to have poorer event-free survival (EFS). T-Cell ALL, Philadelphia chromosome positive (Ph+) and Ph-like ALL subtypes have suboptimal EFS rates and are the focus of new treatment approaches within the Children’s Oncology Group.
For newly diagnosed T-Cell ALL patients who remain in first remission, the EFS rate is similar to high-risk B lineage ALL, but outcomes for patients with relapsed T-Cell ALL are dismal, with a 3-year EFS rate of < 15%, due to chemotherapy resistance and lack of responsiveness to salvage/relapsed treatment. herefore, the current COG study, AALL1231, is investigating the utility of bortezomib, a protease inhibitor, in preventing relapse by overcoming chemotherapy resistance and sensitizing T-ALL cells to steroid therapy. For Ph+ ALL, the overall induction remission rate is 89%, but the 7-year overall survival rate, prior to the addition of continuous tyrosine kinase inhibitor (TKI) therapy, was only 45%.3 The COG study AALL0031, which added continuous TKI therapy for patients with Ph+ ALL, aims to significantly improve EFS, but the data are not yet mature for publication. Ph-like ALL is a recently identified ALL subtype that expresses gene mutations within the tyrosine kinase, CRLF2 and/or JAK/STAT pathways. The overall 5-year EFS for the Ph-like ALL subtype, identified from biology samples on the previous high risk (HR) B ALL trial (AALL0232), was 62.6 %.4 The current HR B-ALL COG trial (AALL1131) includes a plan to transition patients with an identified TKI-sensitive Ph-like mutation to receive added dasatinib therapy and to offer patients with an identified CRLF2 and/or JAK pathway mutation the option of enrolling on AALL1521 to receive ruxolitinib. During this session, current therapy, innovative approaches to care, and future directions for the treatment of patients with T-Cell, Ph+, and Ph-like ALL subtypes will be discussed, providing learners with new knowledge that can be used in daily practice.
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