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Minimal Residual Disease–Based Risk-Directed Therapy Is Effective in Children With BCR-ABL1–Like B-Cell ALL

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Key Points

  • Genomic CRLF2 rearrangement, fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and Ras signaling pathway mutations were found in children with BCR-ABL1–like ALL.
  • There was no difference in event-free or overall survival in children with vs without BCR-ABL1–like ALL.

BCR-ABL1–like acute lymphoblastic leukemia (ALL), a recently identified B-cell ALL subtype associated with poor outcome, has a gene-expression profile similar to BCR-ABL1–positive disease without the presence of the BCR-ABL1 fusion protein. In a retrospective analysis reported in the Journal of Clinical Oncology, Roberts et al found that risk-directed therapy based on minimal residual disease during remission induction produced similar outcomes in children with B-cell ALL with vs without the BCR-ABL1–like subtype.

Study Details

The study involved 344 patients with B-cell ALL from the Total Therapy XV study (2000–2007) with adequate samples for gene expression profiling. In the trial, patients with ≥ 1% residual leukemia on day 19 of remission induction received additional asparaginase induction doses. Minimal residual disease was assessed at the end of induction and patients received consolidation therapy with high-dose methotrexate and daily mercaptopurine for four courses; low-risk and standard-risk patients then received risk-directed continuation therapy, and high-risk patients were offered the option of allogeneic hematopoietic stem-cell transplantation.

Characteristics and Outcomes

Of the 344 patients, 40 (12%) had BCR-ABL1–like ALL. These patients were significantly more likely to be male (P = .04), have Down syndrome (P = .003), and have higher minimal residual disease levels on day 19 (P = .009) and at the end of induction (P = .001).

There was no significant difference in distribution of risk groups between patients with BCR-ABL1–like ALL and those with other B-cell ALL on the basis of initial risk classification; after including response to remission induction based on minimal residual disease level, patients with BCR-ABL1–like ALL were more likely to have standard- or high-risk ALL (P = .02).

Among 25 BCR-ABL1–like ALL patients studied for genetic abnormalities, 11 (44%) had genomic rearrangement of CRLF2, 6 (24%) had fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and 7 (28%) had mutations involving the Ras signaling pathway.

For patients with vs without BCR-ABL1–like ALL, 5-year event-free survival was 90.0% vs 88.4% (P = .41) and 5-year overall survival was 92.5% vs 95.1% (P = .41).

The investigators concluded, “Patients who have BCR-ABL1-like ALL with poor initial treatment response can be salvaged with [minimal residual disease–]based risk-directed therapy and may benefit from identification of kinase-activating lesions for targeted therapies.”

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by grants from the National Institutes of Health, American Lebanese and Syrian Associated Charities, National Health and Medical Research Council (Australia), Leukemia and Lymphoma Society, Alex’s Lemonade Stand Foundation, and Stand Up to Cancer.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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