Feasibility of HLA-haploidentical hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for advanced pediatric malignancies.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 8700164 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-0669 (Electronic) Linking ISSN: 08880018 NLM ISO Abbreviation: Pediatr Hematol Oncol Subsets: MEDLINE

Publication: 2006- : London : Informa Healthcare
Original Publication: Washington, DC : Hemisphere Pub. Corp., c1986-

Hematopoietic Stem Cell Transplantation* ; Peripheral Blood Stem Cell Transplantation*; Cyclophosphamide/*therapeutic use ; Immunosuppressive Agents/*therapeutic use ; Neoplasms/*therapy; Child ; Cyclophosphamide/administration & dosage ; Female ; Graft vs Host Disease/epidemiology ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Haploidy ; Hematologic Neoplasms/blood ; Hematologic Neoplasms/complications ; Hematologic Neoplasms/therapy ; Histocompatibility Testing ; Humans ; Immunosuppressive Agents/administration & dosage ; Japan ; Male ; Neuroblastoma/blood ; Neuroblastoma/complications ; Neuroblastoma/therapy ; Prospective Studies ; Transplantation, Homologous

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.

Keywords: HLA-haploidentical HSCT; PTCY; cyclophosphamide; pediatrics

0 (Immunosuppressive Agents)
8N3DW7272P (Cyclophosphamide)

Date Created: 20141018 Date Completed: 20150731 Latest Revision: 20141106

20250114

10.3109/08880018.2014.961214

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