title: Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.
abstract: In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.
authors.affiliation: Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.|Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development, Tokyo, Japan.|Department of Pediatrics, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Hematology/Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishimaru
authors.affiliation: Department of Pediatrics, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Seki
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shiraishi
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kakiuchi
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, University of Yamanashi, Yamanashi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inukai
authors.affiliation: Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Tomizawa
authors.affiliation: Department of Pediatrics, St Luke's International Hospital, Tokyo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Hasegawa
authors.affiliation: Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.|Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Osumi
authors.affiliation: Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Arakawa
authors.affiliation: Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Department of Pediatrics, Dokkyo Medical University, Shimotsuga, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okuya
authors.affiliation: Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kaizu
authors.affiliation: Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Pediatrics, Chiba Children's Hospital, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Taneyama
authors.affiliation: Division of Hemato-oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Goto
authors.affiliation: Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Taki
authors.affiliation: Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takagi
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sanada
authors.affiliation: Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koh
authors.affiliation: Department of Pediatrics, University of Tokyo, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Takita
authors.affiliation: Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Miyano
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ohara
authors.affiliation: Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsuchida
authors.affiliation: Department of Pediatrics, St Luke's International Hospital, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Manabe
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D060046:Maintenance Chemotherapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D014178:Translocation, Genetic; D016896:Treatment Outcome