title: Non-myeloablative conditioning for second hematopoietic cell transplantation for graft failure in patients with non-malignant disorders: a prospective study and review of the literature.
abstract: Allogeneic hematopoietic cell transplantation (HCT) effectively treats several non-malignant disorders such as selected lysosomal disorders, cerebral adrenoleukodystrophy and hemoglobinopathies. However, rates of graft failure (GF) in non-malignant populations exceed those of patients with malignant indications for HCT. Salvage conditioning regimens and outcomes for second HCT for GF vary immensely in the literature. We report 17 consecutive pediatric patients with non-malignant disorders who underwent a second allogenic HCT for GF using a non-myeloablative, low-dose busulfan-based regimen. Graft sources for the second transplant included umbilical cord blood, unrelated bone marrow and unrelated PBSCs. Median age at time of second HCT was 6.6 years (1.1-14.6 years). Fourteen of seventeen patients (82%) achieved engraftment, with a 3-year overall survival of 82% (95% CI, 54-94%). Day 100 transplant-related mortality was 12% (95% CI, 0-27%). CMV and adenovirus reactivation occurred in 30% and fungal infections in 18%. The incidence of grade II-IV acute GvHD disease was 35% (95% CI, 13-58%) with only 6% grade III-IV (95% CI, 0-17%). In summary, we illustrate excellent overall survival and acceptable toxicity using a non-myeloablative conditioning regimen for second HCT as salvage therapy for first GF in patients with non-malignant conditions.
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mallhi
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: W P
authors.initials: WP
authors.lastname: Miller
authors.affiliation: Biostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Lund
mesh_terms: D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000628:therapy; D002066:Busulfan; D002648:Child; D002675:Child, Preschool; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007223:Infant; D007239:Infections / Q000209:etiology; D008059:Mucopolysaccharidosis I / Q000628:therapy; D016879:Salvage Therapy / Q000379:methods*; D013234:Stem Cells / Q000166:cytology; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D002066:Busulfan