Prospective study of a therapeutic regimen with all-trans retinoic acid and anthracyclines in combination of cytarabine in children with acute promyelocytic leukaemia: the Japanese childhood acute myeloid leukaemia cooperative study.
In childhood acute promyelocytic leukaemia (APL), the efficacy of therapy combining cytarabine with all-trans retinoic acid (ATRA) and anthracyclines remains unclear in terms of long-term prognosis. Between August 1997 and March 2004, 58 children with APL (median age: 11 years) were enrolled into an acute myeloid leukaemia (AML) study (AML99-M3) and followed up for a median time of 86 months. The regimen included ATRA and anthracyclines combined with cytarabine in both induction and consolidation. In induction, two patients died of haemorrhage and four patients developed retinoic acid syndrome. Of 58 patients, 56 (96·6%) achieved complete remission, two of whom relapsed in the bone marrow after 15 and 19 months respectively. Sepsis was a major complication, with an incidence of 5·6-10·9% in the consolidation blocks, from which all but one of patients recovered. Consequently, 7-year overall and event-free survival rates were 93·1% and 91·4% respectively, and cumulative incidence of relapse plateaued at 3·6% after 2 years. Follow-up survey of 54 patients revealed no patients with late cardiotoxicity or secondary malignancy, except one with asymptomatic prolongation of QTc interval. This study suggests that the combination of cytarabine with ATRA and anthracycline-based therapy may have useful implications in the perspective of long-term prognosis and late adverse effects for childhood APL.
Imaizumi
Masue
M
Department of Haematology and Oncology, Miyagi Children's Hospital, Sendai, Japan. imaizumi@miyagi-children.or.jp
Tawa
Akio
A
Hanada
Ryoji
R
Tsuchida
Masahiro
M
Tabuchi
Ken
K
Kigasawa
Hisato
H
Kobayashi
Ryoji
R
Morimoto
Akira
A
Nakayama
Hideki
H
Hamamoto
Kazuko
K
Kudo
Kazuko
K
Yabe
Hiromasa
H
Horibe
Keizo
K
Tsuchiya
Shigeru
S
Tsukimoto
Ichiro
I
D000293:Adolescent; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007223:Infant; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D018365:Neoplasm, Residual; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects
D018943:Anthracyclines; D003561:Cytarabine; D014212:Tretinoin