Appropriate dose reduction in induction therapy is essential for the treatment of infants with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group.
Infants (<1 year old) with acute myeloid leukemia (AML) are particularly vulnerable to intensive cytotoxic therapy. Indeed, the mortality rate was high among infants enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study, which prompted us to temporarily suspend patient enrollment and amend the protocol. Forty-five infants with AML were enrolled. For patients aged <2 years, drug doses were adjusted for body weight. Following the protocol amendments, doses for infants were reduced by a further 33 % in the initial induction course. Six infants died during the induction phase (including five early deaths), mainly due to pulmonary complications. The 3-year probability of overall survival (pOS) in all 45 infants [55.9 %, 95 % confidence interval (CI) 37.9-70.6 %] was significantly lower than that of patients aged 1 to <2 years (77.0 %, 95 % CI 62.7-86.3 %) and those aged ≥2 years (74.7 %, 95 % CI 69.2-79.4 %) (P = 0.037), mainly due to the higher non-relapse mortality rate in infants. No early deaths occurred after the protocol amendments, and the 3-year pOS of the 17 infants enrolled thereafter was 76.4 % (95 % CI 48.8-90.4 %). In conclusion, appropriate dose reduction is essential to avoid early deaths when treating infants with AML.
Department of Pediatrics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan, dtomizawa.ped@tmd.ac.jp.
Daisuke
D
Tomizawa
Akio
A
Tawa
Tomoyuki
T
Watanabe
Akiko Moriya
AM
Saito
Kazuko
K
Kudo
Takashi
T
Taga
Shotaro
S
Iwamoto
Akira
A
Shimada
Kiminori
K
Terui
Hiroshi
H
Moritake
Akitoshi
A
Kinoshita
Hiroyuki
H
Takahashi
Hideki
H
Nakayama
Nobutaka
N
Kiyokawa
Keiichi
K
Isoyama
Shuki
S
Mizutani
Junichi
J
Hara
Keizo
K
Horibe
Tatsutoshi
T
Nakahata
Souichi
S
Adachi
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D012042:Registries; D016896:Treatment Outcome