Improved outcome in childhood acute myeloid leukemia in Singapore with the MRC AML 10 protocol.
BACKGROUND
The introduction of the United Kingdom Medical Research Council's 10th AML trial (MRC AML 10) protocol incorporating high-dose anthracycline therapy has improved outcome of children with acute myeloid leukemia (AML). In this study, we review the results of childhood AML therapy in a Singapore university hospital over the last 17 years emphasizing toxicity and outcome.


METHODS
Retrospective analysis revealed 34 children with AML between 1988 and 2003. Prior to September 1996, therapy consisted of: POG-8498 (n = 10), others (n = 9). From September 1996, all but one of 15 children received MRC AML 10 treatment.


RESULTS
At the time of analysis, 17 had died from disease, and 17 patients were alive among whom 2 had relapsed. MRC AML 10-treated patients (n = 14) had significantly better 3-year overall, event-free, and disease-free survival (74% vs. 35%, 77% vs. 20%, 83% vs. 31%; P = 0.019, P = 0.002, and P = 0.010, respectively) and were likelier to achieve complete remission (CR) than non-MRC AML 10 patients (P = 0.102). Among patients who achieved CR, MRC AML 10-treated patients were significantly more likely to achieve CR after only one cycle of chemotherapy (P = 0.016). Hematologic toxicity was similar among the different regimens (P = 0.9).


CONCLUSIONS
These findings suggest that MRC AML 10 treatment results in significantly superior survival, without excess toxicity. Future studies should attempt to elucidate the relative importance of individual MRC AML 10 components and reduce the high cumulative anthracycline dose without compromising outcome.
Tan
Ronald M
RM
Division of Pediatric Hematology-Oncology, The Children's Medical Institute, National University Hospital, National University of Singapore, Singapore.
Quah
Thuan Chong
TC
Aung
Lele
L
Liang
Shen
S
Kirk
Richard C
RC
Yeoh
Allen E J
AE
D000208:Acute Disease; D000677:Amsacrine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D003906:Developing Countries; D018572:Disease-Free Survival; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006331:Heart Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007239:Infections / Q000209:etiology; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D012189:Retrospective Studies; D012846:Singapore / Q000453:epidemiology; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D000677:Amsacrine; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D008942:Mitoxantrone; D015122:Mercaptopurine; D013866:Thioguanine; D001374:Azacitidine; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin