title: Salvage therapy for children with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: BACKGROUND
  In the tyrosine kinase inhibitor (TKI) era, outcomes after salvage therapy for relapsed or refractory Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remain unclear.
  
  
  METHODS
  The clinical courses of 19 patients with relapse (n = 13) or induction failure (n = 6) in the Japanese Pediatric Leukemia/Lymphoma Study Group Ph+ ALL04 study were retrospectively reviewed.
  
  
  RESULTS
  Fifteen male and four female patients had a median age of 8 (range 4-15) years at relapse or induction failure. Patients received imatinib in combination with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and methotrexate and cytarabine (MTX/Ara-C) (n = 9), imatinib in combination with other chemotherapy (n = 5), chemotherapy without imatinib (n = 2), imatinib alone (n = 2), or no additional chemotherapy (n = 1). Two patients underwent hematopoietic stem cell transplantation (HSCT) without achieving complete remission (CR) and died of leukemia. The remaining 17 patients achieved CR with salvage therapies and underwent HSCT whilst in CR: 10 patients remain alive in CR, five died of transplantation-related complications, and two died of relapse. In six of seven patients with available data on minimal residual disease (MRD), imatinib in combination with the first course of hyper-CVAD was more effective in achieving a favorable MRD response compared with the Ph+ ALL04 induction regimen.
  
  
  CONCLUSIONS
  This study suggested that cross-resistance to imatinib failed to develop after conventional chemotherapy. Imatinib in combination with chemotherapy including hyper-CVAD+MTX/Ara-C was effective and safe for relapsed or refractory Ph+ ALL patients who received frontline therapy without imatinib.
authors.affiliation: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.|Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.affiliation: Department of Pediatrics, Kansai Medical University Hirakata Hospital, Osaka, Japan.
authors.forename: Hirohide
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kato
authors.affiliation: Department of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Hematology and Oncology, Miyagi Children's Hospital, Miyagi, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.affiliation: Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Hiramatsu
authors.affiliation: Department of Pediatric Oncology, Fukushima Medical University Hospital, Fukushima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Sano
authors.affiliation: Department of Hematology and Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Department of Pediatric Hematology and Oncology, Okayama University Hospital, Okayama, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Oda
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
authors.forename: Akiko M
authors.initials: AM
authors.lastname: Saito
authors.affiliation: Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.affiliation: Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.affiliation: Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000628:therapy*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*
chemical_list: D000068877:Imatinib Mesylate
keywords: Philadelphia chromosome positive acute lymphoblastic leukemia; hyper-CVAD; refractory; relapse