title: High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group.
abstract: We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered.
authors.affiliation: Department of Paediatrics, Toho University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Nutritional Science, Faculty of Psychological and Physical Science, Aichi Gakuin University, Nisshin, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Paediatrics, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Department of Haematology-Oncology, Tokyo Metropolitan Children's Medical Centre, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yuza
authors.affiliation: Division of Paediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moritake
authors.affiliation: Department of Paediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Terui
authors.affiliation: Department of Paediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Iwamoto
authors.affiliation: Department of Paediatrics, National Hospital Organization, Fukuoka-Higashi Medical Centre, Fukuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Paediatrics, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.affiliation: Department of Paediatrics, Fujita Health University, Toyoake, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.affiliation: Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Miharu
authors.initials: M
authors.lastname: Yabe
authors.affiliation: Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: Clinical Research Centre, National Hospital Organization Nagoya Medical Centre, Nagoya, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Paediatric Haematology and Oncology, Ibaraki Children's Hospital, Mito, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Koike
authors.affiliation: Department of Paediatrics, Niigata Cancer Centre Hospital, Niigata, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogawa
authors.affiliation: Department of Haematology/Oncology, Hyogo Prefectural Children's Hospital, Kobe, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Division of Leukaemia and Lymphoma, Children's Cancer Centre, National Centre for Child Health and Development, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomizawa
authors.affiliation: Department of Paediatrics, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Taga
authors.affiliation: Clinical Research Centre, National Hospital Organization Nagoya Medical Centre, Nagoya, Japan.
authors.forename: Akiko M
authors.initials: AM
authors.lastname: Saito
authors.affiliation: Clinical Research Centre, National Hospital Organization Nagoya Medical Centre, Nagoya, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.affiliation: Centre for iPS cell research and application, Kyoto University, Kyoto, Japan.
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.affiliation: Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Miyachi
authors.affiliation: Department of Paediatrics, National Hospital Organization, Osaka Medical Centre, Osaka, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tawa
authors.affiliation: Human Health Science, Kyoto University, Kyoto, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
mesh_terms: D000293:Adolescent; D018943:Anthracyclines / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D060830:Consolidation Chemotherapy / Q000379:methods; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007223:Infant; D007564:Japan; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D003561:Cytarabine; D014212:Tretinoin
keywords: acute promyelocytic leukaemia; anthracyclines; childhood leukemia; clinical trial; recombinant human soluble thrombomodulin