title: Repetitive cycles of high-dose cytarabine are effective for childhood acute myeloid leukemia: long-term outcome of the children with AML treated on two consecutive trials of Tokyo Children's Cancer Study Group.
abstract: BACKGROUND
  Various methods of intensive chemotherapy have contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long-term results of the two consecutive trials of Tokyo Children's Cancer Study Group (TCCSG), incorporating repetitive use of high-dose cytarabine (HD-Ara-C) based combination chemotherapy in post-remission phase.
  
  
  METHODS
  A total of 216 eligible children with newly diagnosed AML were treated in the two consecutive multi-center trials of TCCSG, M91-13 and M96-14, from August 1991 to September 1998. In M91-13 trial, patients received eight courses of intensive post-remission chemotherapy, including six HD-Ara-C containing courses, after remission-induction therapy. Autologous hematopoietic stem cell transplantation (HSCT) could be selected by physician's choice, and allogeneic HSCT was allocated if donor was available. In M96-14 trial, the last two HD-Ara-C courses were omitted from the chemotherapy arm.
  
  
  RESULTS
  The remission-induction rate was 88.8% and probability of 5-year Overall survival (OS) and event-free survival (EFS) were 62% (56-69% with 95% Confidence intervals (CIs)) and 56% (49-62%), respectively. Treatment-related mortality (TRM) was 7.8%. Among patients without Down syndrome (DS) or acute promyelocytic leukemia (APL), the presence of t(8;21) or inv(16) was a significant good prognostic factor both in the univariate and multivariate analyses. Children with DS (N = 10) and APL (N = 14) also showed a good survival exceeding 70% in 5 years.
  
  
  CONCLUSIONS
  These results suggest that repetitive use of HD-Ara-C was effective and safe for childhood AML. However, further optimization of AML therapy is required.
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan. dtomizawa.ped@tmd.ac.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomizawa
authors.forename: Ken
authors.initials: K
authors.lastname: Tabuchi
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hanada
authors.forename: Hisato
authors.initials: H
authors.lastname: Kigasawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsukimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchida
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D004314:Down Syndrome / Q000150:complications; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007223:Infant; D007239:Infections / Q000209:etiology / Q000401:mortality; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008942:Mitoxantrone / Q000008:administration & dosage; D012074:Remission Induction; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D014212:Tretinoin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D008942:Mitoxantrone; C027260:pirarubicin; D006854:Hydrocortisone; D008727:Methotrexate