title: Feasibility of HLA-haploidentical hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for advanced pediatric malignancies.
abstract: BACKGROUND
  Patients with advanced malignancies in non-complete remission (CR) have a dismal prognosis after HLA-matched hematopoietic stem cell transplantation (HSCT). T-cell-replete HLA-haploidentical HSCT has remarkable anti-leukemia/tumor effects on these patients, but also a high risk of severe/extensive graft-versus-host disease (GHVD). Post-transplantation cyclophosphamide (PTCY) is regarded as a GVHD-specific immunosuppressant in adults, but its feasibility is unknown in children.
  
  
  METHODS
  We performed a prospective feasibility study of PTCY at 50 mg/kg on day 3 for children with advanced leukemias or malignant solid tumors: refractory to chemotherapy or relapsed after conventional allogeneic HSCT. Conditioning consisted of fludarabine (180 mg/m2) and melphalan (140-210 mg/m2).
  
  
  RESULTS
  Long-term engraftments were achieved in 11 patients (73.3%) after bone marrow transplantation (BMT, n = 13) or peripheral blood (PB) stem cell transplantation (n = 2). The incidence of severe acute GHVD was 25.0% and that of extensive chronic GVHD 0.0% after evaluable BMT. CR was achieved in 6/15 and partial response in 4/15 as the best response. Finally, 11/15 experienced disease progression/relapse, 2/15 suffered treatment-related mortality without evidence of disease, and 2/15 are alive in continuous CR.
  
  
  CONCLUSIONS
  PTCY is feasible in children; however, for a better outcome in such patients with advanced malignancies, some modifications are anticipated.
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health , Izumi City, Osaka , Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sawada
authors.forename: Mariko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Kanako
authors.initials: K
authors.lastname: Isaka
authors.forename: Kouhei
authors.initials: K
authors.lastname: Higuchi
authors.forename: Azusa
authors.initials: A
authors.lastname: Mayumi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yoshimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Kondo
authors.forename: Maho
authors.initials: M
authors.lastname: Koyama-Sato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasui
authors.forename: Keisei
authors.initials: K
authors.lastname: Kawa
authors.forename: Masami
authors.initials: M
authors.lastname: Inoue
mesh_terms: D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D006238:Haploidy; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D009369:Neoplasms / Q000628:therapy*; D009447:Neuroblastoma / Q000097:blood / Q000150:complications / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: HLA-haploidentical HSCT; PTCY; cyclophosphamide; pediatrics