title: Outcome of Reinduction Chemotherapy with a Modified Dose of Idarubicin for Children with Marrow-Relapsed Acute Lymphoblastic Leukemia: Results of the Childhood Acute Lymphoblastic Leukemia (CALL)-0603 Study.
abstract: This multicenter, prospective trial was conducted to develop an effective and safe reinduction regimen for marrow-relapsed pediatric acute lymphoblastic leukemia (ALL) by modifying the dose of idarubicin. Between 2006 and 2009, the trial accrued 44 patients, 1 to 21 years old with first marrow-relapsed ALL. The reinduction regimen comprised prednisolone, vincristine, L-asparaginase, and idarubicin (10 mg/m²/week). The idarubicin dose was adjusted according to the degree of myelosuppression. The second complete remission (CR2) rate was 72.7%, obtained by 54.2% of patients with early relapse < 24 months after initial diagnosis and 95.0% of those with late relapse (P = 0.002). Five patients entered remission with extended treatment, resulting in a final CR2 rate of 84.1%. The CR2 rate was not significantly different according to the idarubicin dose. The induction death rate was 2.3% (1/44). The 5-year event-free and overall survival rates were 22.2% ± 6.4% and 27.3% ± 6.7% for all patients, 4.2% ± 4.1% and 8.3% ± 5.6% for early relapsers, and 43.8% ± 11.4% and 50.0% ± 11.2% for late relapsers, respectively. Early relapse and slow response to reinduction chemotherapy were predictors of poor outcomes. In conclusion, a modified dose of idarubicin was effectively incorporated into the reinduction regimen for late marrow-relapsed ALL with a low toxic death rate. However, the CR2 rate for early relapsers was suboptimal, and the second remission was not durable in most patients.
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
authors.forename: Kyung Nam
authors.identifier: http://orcid.org/0000-0002-6376-672X
authors.initials: KN
authors.lastname: Koh
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
authors.forename: Ho Joon
authors.identifier: http://orcid.org/0000-0001-8799-4068
authors.initials: HJ
authors.lastname: Im
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea.
authors.forename: Hyery
authors.identifier: http://orcid.org/0000-0003-2852-6832
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Hyoung Jin
authors.identifier: http://orcid.org/0000-0003-1009-6002
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Kyung Duk
authors.identifier: http://orcid.org/0000-0002-6943-4398
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Hee Young
authors.identifier: http://orcid.org/0000-0003-2091-1947
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Hyo Seop
authors.identifier: http://orcid.org/0000-0002-5618-7033
authors.initials: HS
authors.lastname: Ahn
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Won
authors.identifier: http://orcid.org/0000-0003-0084-1304
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Keon Hee
authors.identifier: http://orcid.org/0000-0002-5980-7912
authors.initials: KH
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ki Woong
authors.identifier: http://orcid.org/0000-0001-5989-4772
authors.initials: KW
authors.lastname: Sung
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hong Hoe
authors.identifier: http://orcid.org/0000-0001-8082-1412
authors.initials: HH
authors.lastname: Koo
authors.affiliation: Department of Pediatrics, Pusan National University College of Medicine, Busan, Korea.
authors.forename: Young Tak
authors.identifier: http://orcid.org/0000-0002-3300-7239
authors.initials: YT
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, Ajou University College of Medicine, Suwon, Korea.
authors.forename: Jun Eun
authors.identifier: http://orcid.org/0000-0003-4292-3500
authors.initials: JE
authors.lastname: Park
authors.affiliation: Center for Pediatric Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Byung Kiu
authors.identifier: http://orcid.org/0000-0001-9743-0610
authors.initials: BK
authors.lastname: Park
authors.affiliation: Center for Pediatric Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Hyeon Jin
authors.identifier: http://orcid.org/0000-0002-9557-3412
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children's Hospital, Seoul, Korea. jjseo@amc.seoul.kr.
authors.forename: Jong Jin
authors.identifier: http://orcid.org/0000-0002-0191-7836
authors.initials: JJ
authors.lastname: Seo
mesh_terms: D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone; D015255:Idarubicin
keywords: Acute Lymphoblastic Leukemia; Childhood; Idarubicin; Induction; Relapse