title: Comparison of chemotherapeutic agents as a myeloablative conditioning with total body irradiation for pediatric acute lymphoblastic leukemia: A study from the pediatric ALL working group of the Japan Society for Hematopoietic Cell Transplantation.
abstract: BACKGROUND
  As a partner of total body irradiation (TBI) in hematopoietic stem cell transplantation (HSCT) for pediatric acute lymphoblastic leukemia (ALL), various cytotoxic agents are used, but the optimal combination is still unclear.
  
  
  METHODS
  We retrospectively analyzed 767 children who received TBI-based myeloablative allogeneic HSCT in complete remission (CR), using nationwide registry data of the Japan Society for Hematopoietic Cell Transplantation. Combinations of chemotherapy were categorized as follows: cyclophosphamide (CY) (n = 74), melphalan (L-PAM) (n = 139), CY + etoposide (VP16) (n = 408), CY + cytarabine (AraC) (n = 73), and others (n = 73).
  
  
  RESULTS
  Event-free survival (EFS) at 5 years after HSCT was 62.2% for CY, 71.4% for L-PAM, 67.6% for CY + VP16, 52.6% for CY + AraC, and 59.1% for others (P = 0.009). Further detailed comparison of LPAM and CY + VP16 demonstrated superior EFS for LPAM (83.2 ± 6.7%), with a marked difference compared with CY + VP16 (66.7 ± 4.9%) when limited to HSCT from a matched related donor (MRD), and this result was reproduced regardless of disease status (CR1 or CR2). However, EFS for CY + VP16 (68.3 ± 2.8%) was comparable to that for LPAM (64.5 ± 5.7%, P = 0.37) in HSCT from alternative donors, because higher non-relapse mortality attenuated the advantage of LPAM.
  
  
  CONCLUSIONS
  For pediatric ALL in remission, LPAM could provide superior EFS for HSCT from MRD; however, compared to LPAM, CY + VP16 has similar EFS for HSCT from an alternative donor.
authors.affiliation: Department of Pediatrics, University of Tokyo, Tokyo, Japan.|Department of Cell Therapy and Transplantation Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Pediatrics, Matsushita Memorial Hospital, Moriguchi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Koh
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Inagaki
authors.affiliation: Department of Hematology/Oncology, Ibaraki Children's Hospital, Mito, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kato
authors.affiliation: Division of Hemato-oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Goto
authors.affiliation: Division of Hematology and Oncology, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, Osaka University Hospital, Suita, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hashii
authors.affiliation: Department of Pediatrics, Dokkyo University Hospital, Shimotsuga, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kurosawa
authors.affiliation: Department of Pediatrics, University of Tokyo, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Takita
authors.affiliation: Department of Pediatrics, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hamamoto
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sawada
authors.affiliation: Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents
keywords: acute lymphoblastic leukemia; chemotherapeutic agents; conditioning regimen; stem cell transplantation; total body irradiation