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- DOI: 10.1182/blood-2013-06-509794
- PMID: 24366361
- UKPMCID: 24366361
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IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL.
van der Veer, Arian; Zaliova, Marketa; Mottadelli, Federica; De Lorenzo, Paola; Te Kronnie, Gertruuy; Harrison, Christine J; Cavé, Hélène; Trka, Jan; Saha, Vaskar; Schrappe, Martin; Pieters, Rob; Biondi, Andrea; Valsecchi, Maria Grazia; Stanulla, Martin; den Boer, Monique L; Cazzaniga, Giovanni
Blood. 2014;123(11):1691-1698.
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Full-text held externally
- DOI: 10.1182/blood-2013-06-509794
- PMID: 24366361
- UKPMCID: 24366361
Abstract
Childhood BCR-ABL1-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has an unfavorable outcome and is characterized by a high frequency of IKZF1 deletions. The prognostic value of IKZF1 deletions was evaluated in two cohorts of children with BCR-ABL1-positive BCP-ALL, before (pre-TKI) and after introduction of Imatinib (EsPhALL). IKZF1 deletions were found in 126/191 (66%) of the patients. In the pre-TKI cohort, IKZF1-deleted patients had an unfavorable outcome compared to wild-type patients (4-yr DFS 30.0±6.8% versus 57.5±9.4%, p=0.01). In the EsPhALL-cohort, the IKZF1 deletions were associated with an unfavorable prognosis in patients who were stratified by early clinical response in the good-risk arm (4-yr DFS 51.9±8.8% for IKZF1-deleted versus 78.6±13.9% for IKZF1 wild-type; p=0.03), even when treated with Imatinib (4-yr DFS 55.5±9.5% for IKZF1-deleted versus 75.0±21.7% for IKZF1 wild-type; p=0.05). In conclusion, IKZF1 deletions are predictive for a highly unfavorable outcome in children with BCR-ABL1-positive BCP-ALL irrespective the introduction of Imatinib. These results underscore the urgent need for alternative therapy for IKZF1-deleted BCR-ABL1-positive patients. In contrast, good-risk patients with IKZF1 wild-type responded remarkably well to Imatinib-containing regimens, thus providing a rationale to potentially avoid the use of hematopoietic stem cell transplantation in this subset of BCR-ABL1-positive children.