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MRD-directed therapy improved outcomes in pediatric BCR-ABL1–like ALL
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Pediatric patients with BCR-ABL1–like acute lymphoblastic leukemia who received risk-directed therapy based on minimal residual disease levels during remission induction demonstrated similar outcomes as patients with other B-cell ALL subtypes, according to study results.
The identification of kinase-activating lesions for targeted therapies may further improve survival in this subgroup, results showed.
Kathryn G. Roberts, PhD, of St Jude Children’s Research Hospital, and colleagues sought to evaluate outcomes of patients with BCR-ABL1–like ALL — a recently identified disease subtype that has a similar gene expression as BCR-ABL1–positive ALL without the BCR-ABL1 fusion protein — due to the inferior outcomes previously demonstrated by these patients.
The analysis included 344 patients with B-cell ALL who were enrolled on the Total Therapy XV study. Forty (11.6%) of the patients had BCR-ABL1-like ALL.
Patients with BCR-ABL1-like ALL were more likely to be male (P=.04), have Down syndrome (P=.003) and present with higher MRD on day 19 (P=.009) and at the end of induction therapy (P=.001) compared with patients with other B-cell ALL subtypes.
Researchers treated patients according to MRD-based risk stratification. A greater proportion of patients with BCR-ABL1-like ALL compared with other B-cell ALL subtypes were identified as high risk and underwent hematopoietic stem-cell transplantation (15% vs. 4.3%; P=.015).
Twenty-five patients with BCR-ABL1-like ALL underwent extensive genetic analyses. Eleven patients had genomic rearrangements of CRLF2, six had ABL TKI- or JAK inhibitor-responsive fusion transcripts, and seven harbored RAS signaling pathway mutations.
A higher percentage of patients with BCR-ABL1–like ALL achieved 5-year EFS compared with those who had other subtypes (90% vs. 88.4%; P=.41), but the difference was not statistically significant. Rates for 5-year OS also were comparable between patients with and without BCR-ABL1–like ALL (92.5% vs. 95.1%; P=.41).
“The advances in cure rates brought about by contemporary MRD-based treatment of childhood ALL have extended to patients with BCR-ABL1–like ALL despite their initial inferior response to treatment,” Roberts and researchers concluded. “Identification of this ALL subtype and administration of targeted therapy may further improve overall cure rates beyond 90% achieved in some of the contemporary clinical trials and improve their quality of life.”
Disclosure: One researcher reports royalties from the patent of a relevant genetic assay.
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