title: Non-total body irradiation myeloablative conditioning with intravenous busulfan and cyclophosphamide in hematopoietic stem cell transplantation for malignant infantile osteopetrosis.
abstract: HSCT is the only curative treatment for MIOP. We prospectively investigated the outcome of HSCT using intravenous busulfan-based conditioning regimen from 2008 to 2013. Nineteen patients (median age = 17 months) underwent transplantation from HLA-matched related donors (n = 14), HLA-haploidentical related donors (n = 2), partially matched cord blood donors (n = 2), and HLA-matched unrelated donor (n = 1). Bone marrow (n = 9), peripheral blood (n = 8), and cord blood (n = 2) were used as stem cell sources. All but one patient demonstrated primary engraftment. Two patients experienced secondary graft failure. During the follow-up period, three patients showed mixed chimerism (45%, 45%, and 70% of donor cells were engrafted in each one of these patients) but are disease free. Two-yr OS and DFS were 84.2% and 73.7%, respectively. Improvement of visual acuity and partial reversal of mild conductive hearing loss occurred in two and four patients, respectively. The causes of death among three patients were infection, GvHD, and disease progression. In conclusion, due to major side effects of MIOP such as visual and hearing loss, early treatment using myeloablative conditioning without irradiation HSCT is suggested. The use of an HLA-matched related donor seems to be highly successful in this regard. Also, according to results of our study, mixed chimerism may be sufficient to resolve symptoms of disease.
authors: Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Maryam
authors: M
authors: Behfar
authors: S Sharareh
authors: SS
authors: Dehghani
authors: Ashraf Sadat
authors: AS
authors: Hosseini
authors: Arash
authors: A
authors: Jalali
authors: Amir Ali
authors: AA
authors: Hamidieh
authors: Ardeshir
authors: A
authors: Ghavamzadeh
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D002066:Busulfan / Q000008:administration & dosage*; D002675:Child, Preschool; D046528:Chimerism; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease; D006680:HLA Antigens / Q000276:immunology; D006314:Hearing Loss, Conductive / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007223:Infant; D008297:Male; D010022:Osteopetrosis / Q000628:therapy*; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D014916:Whole-Body Irradiation
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan
keywords: hematopoietic stem cell transplantation; malignant infantile osteopetrosis; myeloablative conditioning regimen