IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL

Arian Van Der Veer, Marketa Zaliova, Federica Mottadelli, Paola De Lorenzo, Gertruuy Te Kronnie, Christine J. Harrison, Hélène Cavé, Jan Trka, Vaskar Saha, Martin Schrappe, Rob Pieters, Andrea Biondi, Maria Grazia Valsecchi, Martin Stanulla, Monique L. Den Boer, Giovanni Cazzaniga

    Research output: Contribution to journalArticlepeer-review


    Childhood BCR-ABL1-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has an unfavorable outcome and shows high frequency of IKZF1 deletions. The prognostic value of IKZF1 deletions was evaluated in 2 cohorts of BCR-ABL1-positive BCP-ALL patients, before tyrosine kinase inhibitors (pre-TKI) and after introduction of imatinib (in the European Study for Philadelphia-Acute Lymphoblastic Leukemia [EsPhALL]). In 126/191 (66%) cases an IKZF1 deletion was detected. In the pre-TKI cohort, IKZF1-deleted patients had an unfavorable outcome compared with wild-type patients (4-year disease-free survival [DFS] of 30.0 ± 6.8% vs 57.5 ± 9.4%; P = .01). In the EsPhALL cohort, the IKZF1 deletions were associated with an unfavorable prognosis in patients stratified in the good-risk arm based on early clinical response (4-year DFS of 51.9 ± 8.8% for IKZF1-deleted vs 78.6 ± 13.9% for IKZF1 wild-type; P = .03), even when treated with imatinib (4-year DFS of 55.5 ± 9.5% for IKZF1-deleted vs 75.0 ± 21.7% for IKZF1 wild-type; P = .05). In conclusion, the highly unfavorable outcome for childhood BCR-ABL1-positive BCP-ALL with IKZF1 deletions, irrespective of imatinib exposure, underscores the need for alternative therapies. In contrast, good-risk patients with IKZF1 wild-type responded remarkably well to imatinib-containing regimens, providing a rationale to potentially avoid hematopoietic stem-cell transplantation in this subset of patients. © 2014 by The American Society of Hematology.
    Original languageEnglish
    Pages (from-to)1691-1698
    Number of pages7
    Issue number11
    Early online date23 Dec 2013
    Publication statusPublished - 13 Mar 2014


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