title: Intensified and prolonged therapy comprising cytarabine, vincristine and prednisolone improves outcome in patients with multisystem Langerhans cell histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study.
abstract: The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was performed to further improve the prognosis from 2002 to 2009. The present study compared the therapeutic results of these two studies in terms of multisystem disease. All patients were treated with 6 weeks of the Induction A regimen, comprising cytarabine, vincristine and prednisolone, followed by maintenance therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has been revised from JLSG-96 in the following respects: prednisolone dosage during Induction A increased; duration of maintenance therapy extended from 24 to 48 weeks; cyclosporine introduced to Induction B for progressive disease. One hundred forty-seven children with multisystem LCH were evaluated. Of these, 84 were positive for risk of organ involvement (RO) and 63 were RO-negative. At the 6-week point, 76.2 % of RO+ and 93.7 % of RO- patients responded to Induction A. Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5-56.9] for RO+ and 69.7 % (58.4-81.1) for RO-, which was significantly superior to that in JLSG-96 [26.8 % (13.3-40.4) and 38.9 % (16.4-61.4), respectively]. The intensified induction and prolonged maintenance regimens in JLSG-02 improved EFS in patients with multisystem LCH.
authors.affiliation: Department of Pediatrics, Jichi Medical University of Medicine, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. akira@jichi.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.affiliation: Pediatric Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shioda
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: Division of Hematology/Oncology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakashita
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasui
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Koga
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.affiliation: National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Fujimoto
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.affiliation: Department of Pediatrics, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Bessho
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tsunematsu
authors.affiliation: Department of Laboratory Medicine, Uji-Tokushukai Medical Center, Uji, Kyoto, Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols / Q000592:standards*; D016572:Cyclosporine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination / Q000379:methods*; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D009102:Multiple Organ Failure; D011239:Prednisolone / Q000008:administration & dosage; D012074:Remission Induction / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014750:Vincristine; D016572:Cyclosporine; D011239:Prednisolone
keywords: Chemotherapy; Clinical trials; Langerhans cell histiocytosis