title: Impact of IKZF1 deletions on long-term outcomes of allo-SCT following imatinib-based chemotherapy in adult Philadelphia chromosome-positive ALL.
abstract: We investigated the prognostic relevance of IKZF1 deletions in 118 adult Ph-positive ALL patients who had minimal residual disease (MRD) data under a uniform treatment of allo-SCT following first-line imatinib-based chemotherapy. IKZF1 deletions were identified in 93 patients (78.8%). IKZF1-deleted patients had a lower proportion of early-stable molecular responders compared with wild-type patients (28.0 vs 56.0%, P=0.028). After a median follow-up of 72 months, IKZF1-deleted patients had a trend for higher cumulative incidence of relapse (CIR) (38.0 vs 13.3%, P=0.052), particularly in a subgroup of early-stable molecular responders (n=40; 21.4 vs 0%, P=0.088), but comparable disease-free survival to wild-type patients. Patients with biallelic-null deletions showed higher CIR (74.6 vs 13.3%, P=0.003) and lower disease-free survival (20.0 vs 67.5%, P=0.022) than wild-type patients. In multivariate analysis, MRD kinetics were closely related to outcomes, while neither IKZF1 deletions nor their functional subtypes retained an independent statistical power. Within the limitation of sample size, however, considering both the negative impact of IKZF1 deletions on MRD kinetics and a trend for relationship between IKZF1 deletions and relapse in early-stable molecular responders, IKZF1 deletions may have a potentially additive effect on unfavorable prognosis in a specific MRD-based subgroup of adult Ph-positive ALL transplants.
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: D-W
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Jeon
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: S-A
authors.initials: SA
authors.lastname: Yahng
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: S-E
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: B-S
authors.initials: BS
authors.lastname: Cho
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: K-S
authors.initials: KS
authors.lastname: Eom
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: C-Ki
authors.initials: CK
authors.lastname: Min
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: S-G
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: J-W
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: W-S
authors.initials: WS
authors.lastname: Min
authors.affiliation: Department of Hematology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D051740:Ikaros Transcription Factor / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D017384:Sequence Deletion; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C497239:IKZF1 protein, human; D010879:Piperazines; D011743:Pyrimidines; D051740:Ikaros Transcription Factor; D000068877:Imatinib Mesylate