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    acute lymphoblastic leukemia

    Key Predictors of Remission in Philadelphia Chromosome-Positive ALL

    Publication Title: Predictors of complete molecular response and impact of allogeneic hematopoietic stem cell transplantation on outcome in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL): results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)

    Summary

    Question
    This study examined predictors of complete molecular response (CMR) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and assessed the impact of allogeneic hematopoietic stem cell transplantation (allo-HCT) on outcomes. CMR refers to the absence of detectable BCR::ABL1 fusion transcripts, a genetic marker driving the disease.
    Why it Matters
    Ph+ ALL is a rare and aggressive blood cancer characterized by a genetic mutation called the Philadelphia chromosome, which leads to uncontrolled cell growth. Historically associated with poor survival, advancements in targeted therapies like tyrosine kinase inhibitors (TKIs) have improved outcomes. Understanding predictors of early remission and the role of allo-HCT is crucial for optimizing treatment strategies, minimizing relapse risk, and improving long-term survival for patients.
    Methods
    The researchers conducted a retrospective study across 14 academic institutions, analyzing data from 467 adults treated for Ph+ ALL between 2003 and 2023. They evaluated factors influencing CMR at three months post-treatment initiation and compared survival outcomes between patients who underwent allo-HCT and those who did not.
    Key Findings
    CMR was achieved in 63.7% of patients. Factors negatively affecting CMR included high white blood cell counts at diagnosis (>70,000/L), the p210 BCR::ABL1 fusion subtype, and monosomy 7 (a chromosomal abnormality). Patients treated with second- or third-generation TKIs (dasatinib or ponatinib) and intensive chemotherapy were more likely to achieve CMR. Among patients who achieved CMR, relapse-free survival was significantly longer for those who underwent allo-HCT (123.1 months versus 30.3 months), though overall survival was similar with or without allo-HCT.
    Implications
    The findings suggest that patients achieving early CMR may not require allo-HCT to improve overall survival, potentially sparing them from the procedure's risks. Targeted therapies like dasatinib and ponatinib are effective in promoting remission. Identifying high-risk factors, such as monosomy 7, can guide personalized treatment strategies and highlight patients who may benefit from more aggressive interventions.
    Next Steps
    The authors recommend further prospective studies to validate these findings and explore chemotherapy-free approaches combining TKIs with immunotherapy, such as blinatumomab. They also emphasize the need for research into the role of specific genetic mutations, such as monosomy 7, in predicting treatment resistance and long-term outcomes.
    Funding Information
    The authors reported there is no funding associated with the work featured in this article. Yale University also provided funding and support for this research.

    Full Citation

    Mohty R, Narra R, Mims A, Hunter C, Shallis R, Kota V, Jamy O, Coltoff A, Othman T, Jonas B, Patel A, DuVall A, Foucar C, Abdelsamia M, Palmisiano N, Patel S, Curran E, Omer Z, Advani A, Atallah E, Litzow M, Badar T. Predictors of complete molecular response and impact of allogeneic hematopoietic stem cell transplantation on outcome in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL): results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Leukemia & Lymphoma 2026, ahead-of-print: 1-8. PMID: 41954351, DOI: 10.1080/10428194.2026.2650679.

    Authors

    • Razan Mohty

      First Author
      School Building Streamline Icon: https://streamlinehq.comOther Institution

    • Talha Badar

      Last Author
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    Yale School of Medicine Authors

    Other Authors

    • Ravi Narra;
    • Alice S. Mims;
    • Cameron Hunter;
    • Vamsi Kota;
    • Omer Jamy;
    • Alexander Coltoff;
    • Tamer Adel Othman;
    • Brian A. Jonas;
    • Anand A. Patel;
    • Adam S. DuVall;
    • Charles E. Foucar;
    • Mahmoud Abdelsamia;
    • Neil Palmisiano;
    • Shyam A. Patel;
    • Emily Curran;
    • Zulfa Omer;
    • Anjali Advani;
    • Ehab Atallah;
    • Mark R. Litzow

    Research Themes

    Concepts