title: IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands;
authors.forename: Arian
authors.initials: A
authors.lastname: van der Veer
authors.forename: Marketa
authors.initials: M
authors.lastname: Zaliova
authors.forename: Federica
authors.initials: F
authors.lastname: Mottadelli
authors.forename: Paola
authors.initials: P
authors.lastname: De Lorenzo
authors.forename: Gertruuy
authors.initials: G
authors.lastname: Te Kronnie
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.forename: Vaskar
authors.initials: V
authors.lastname: Saha
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Monique L
authors.initials: ML
authors.lastname: den Boer
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D002648:Child; D002869:Chromosome Aberrations; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D000068877:Imatinib Mesylate; D008297:Male; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use; D017384:Sequence Deletion; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C497239:IKZF1 protein, human; D010879:Piperazines; D011743:Pyrimidines; D051740:Ikaros Transcription Factor; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl