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.
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.
Tomizawa
Daisuke
D
Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan. dtomizawa.ped@tmd.ac.jp
Tabuchi
Ken
K
Kinoshita
Akitoshi
A
Hanada
Ryoji
R
Kigasawa
Hisato
H
Tsukimoto
Ichiro
I
Tsuchida
Masahiro
M
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
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D014212:Tretinoin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D008942:Mitoxantrone; C027260:pirarubicin; D006854:Hydrocortisone; D008727:Methotrexate