Outcomes of children with BCR-ABL1–like acute lymphoblastic leukemia treated with risk-directed therapy based on the levels of minimal residual disease

BCR-ABL1–like acute lymphoblastic leukemia (ALL) is a recently identified B-cell ALL (B-ALL)subtype with poor outcome that exhibits a gene expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion protein. We examined the outcome of children with BCR-ABL1–like ALL treated wit...

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Vydáno v:	Journal of clinical oncology Ročník 32; číslo 27; s. 3012
Hlavní autoři:	Roberts, Kathryn G, Pei, Deqing, Campana, Dario, Payne-Turner, Debbie, Li, Yongjin, Cheng, Cheng, Sandlund, John T, Jeha, Sima, Easton, John, Becksfort, Jared, Zhang, Jinghui, Coustan-Smith, Elaine, Raimondi, Susana C, Leung, Wing H, Relling, Mary V, Evans, William E, Downing, James R, Mullighan, Charles G, Pui, Ching-Hon
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 20.09.2014
Témata:	Adolescent Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Child Child, Preschool Disease-Free Survival Female Fusion Proteins, bcr-abl - drug effects Fusion Proteins, bcr-abl - genetics Gene Expression Profiling Humans Infant Kaplan-Meier Estimate Male Molecular Targeted Therapy - methods Neoplasm, Residual - drug therapy Neoplasm, Residual - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Risk Assessment Risk Factors Salvage Therapy - methods
ISSN:	1527-7755, 1527-7755
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Shrnutí:	BCR-ABL1–like acute lymphoblastic leukemia (ALL) is a recently identified B-cell ALL (B-ALL)subtype with poor outcome that exhibits a gene expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion protein. We examined the outcome of children with BCR-ABL1–like ALL treated with risk-directed therapy based on minimal residual disease (MRD) levels during remission induction. Among 422 patients with B-ALL enrolled onto the Total Therapy XV study between 2000 and 2007, 344 had adequate samples for gene expression profiling. Next-generation sequencing and/or analysis of genes known to be altered in B-ALL were performed in patients with BCR-ABL1–likeALL who had available material. Outcome was compared between patients with and those without BCR-ABL1–like ALL. Forty (11.6%) of the 344 patients had BCR-ABL1–like ALL. They were significantly more likely to be male, have Down syndrome, and have higher MRD levels on day 19 and at the end of induction than did other patients with B-ALL. Among 25 patients comprehensively studied for genetic abnormalities, 11 harbored a genomic rearrangement of CRLF2, six had fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and seven had mutations involving the Ras signaling pathway. There were no significant differences in event-free survival (90.0% +/- 4.7% [SE] v. 88.4% +/- .9% at 5 years; P = .41or in overall survival (92.5% +/- 4.2% v. 95.1% +/- 1.3% at 5 years; P = .41) between patients with and without BCR-ABL1–like ALL. Patients who have BCR-ABL1–like ALL with poor initial treatment response can be salvaged with MRD-based risk-directed therapy and may benefit from identification of kinase-activating lesions for targeted therapies.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1527-7755 1527-7755
DOI:	10.1200/JCO.2014.55.4105