Preserved High Probability of Overall Survival with Significant Reduction of Chemotherapy for Myeloid Leukemia in Down Syndrome: A Nationwide Prospective Study in Japan.
BACKGROUND
On the basis of results of previous Japanese trials for myeloid leukemia in Down syndrome (ML-DS), the efficacy of risk-oriented therapy was evaluated in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-D05 study.


METHODS
All patients received induction chemotherapy that consisted of pirarubicin, intermediate-dose cytarabine, and etoposide. Patients who achieved complete remission (CR) after initial induction therapy were stratified to the standard risk (SR) group and received four courses of reduced-dose intensification therapy. Patients who did not achieve CR were stratified to the high risk (HR) group and received intensified therapy that consisted of continuous or high-dose cytarabine.


RESULTS
A total of 72 patients were eligible and evaluated. One patient died of sepsis during initial induction therapy. Sixty-nine patients were stratified to SR and two patients to HR. No therapy-related deaths were observed during intensification therapy. The 3-year event-free and overall survival rates were 83.3% ± 4.4% and 87.5% ± 3.9%, respectively. Age at diagnosis less than 2 years was a significant favorable prognostic factor for risk of relapse (P = 0.009).


CONCLUSIONS
The attempt of risk-oriented prospective study for ML-DS was unsuccessful, but despite the dose reduction of chemotherapeutic agents, the overall outcome was good, and further dose reduction might be possible for specific subgroups.
Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan.
Takashi
T
Taga
Department of Nutritional Science, Faculty of Psychological and Physical Science, Aichi Gakuin University, Nisshin, Japan.
Tomoyuki
T
Watanabe
Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
Daisuke
D
Tomizawa
Department of Pediatrics, Fujita Health University, Toyoake, Japan.
Kazuko
K
Kudo
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Kiminori
K
Terui
Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Hiroshi
H
Moritake
Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.
Akitoshi
A
Kinoshita
Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
Shotaro
S
Iwamoto
Department of Pediatrics, National Hospital Organization, Fukuoka-Higashi Medical Center, Fukuoka, Japan.
Hideki
H
Nakayama
Department of Pediatrics, Toho University, Tokyo, Japan.
Hiroyuki
H
Takahashi
Department of Pediatrics, Okayama University Hospital, Okayama, Japan.
Akira
A
Shimada
Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tomohiko
T
Taki
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Tsutomu
T
Toki
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Etsuro
E
Ito
Division of Hemato-Oncology and Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
Hiroaki
H
Goto
Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
Katsuyoshi
K
Koh
Laboratory of Clinical, Epidemiological and Health Services Research, Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Aichi, Japan.
Akiko M
AM
Saito
Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
Keizo
K
Horibe
Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Tatsutoshi
T
Nakahata
Department of Pediatrics, National Hospital Organization, Osaka Medical Center, Osaka, Japan.
Akio
A
Tawa
Human Health Sciences, Kyoto University, Kyoto, Japan.
Souichi
S
Adachi
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004314:Down Syndrome / Q000150:complications*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007223:Infant; D007564:Japan; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D011446:Prospective Studies
D003561:Cytarabine; D005047:Etoposide; D004317:Doxorubicin; C027260:pirarubicin
Down syndrome; acute myeloid leukemia; clinical trial