title: A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders.
abstract: Bone marrow transplantation (BMT) benefits nonmalignant diseases but is limited by regimen-related toxicity, graft-versus-host disease (GVHD), donor availability, and graft rejection (GR). To overcome some of these barriers, we developed a new conditioning strategy for these patients. In total, 16 patients received Campath-1H (33/48 mg; days -21 to -19), fludarabine (150 mg/m(2); days -8 to -4), melphalan (140/70 mg/m(2); day -3), and transplant using related/unrelated stem cells. GVHD prophylaxis included cyclosporine/methylprednisolone for cord cells. Other recipients also received methotrexate. Risk factors for GR included multiple transfusions (6), low stem cell numbers (1), and immunologic/metabolic disorders (3). Donor engraftment was present in 14/16 recipients. Neutrophils (ANC>0.5 x 10(9)/l) and platelets (>50 x 10(9)/l) engrafted at a median of 13 and 24 days. Two patients died of Pseudomonas sepsis prior to engraftment, one of CMV disease, and another of intracranial hemorrhage. With median follow-up of 281 days (78-907), 12/16 are stable/improved, or cured. Acute GVHD was absent (n=10) or mild and transient (grade1-2 skin) (n=4). There was no chronic GVHD. Toxicities were predominantly early infections within 100 days, and correlated with lymphopenia (CD4+ T and B cells). Stable engraftment and low incidence of significant GVHD, irrespective of age or stem cell source, make this reduced-intensity regimen attractive for nonmalignant disorders.
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA. shenoy@kids.wustl.edu
authors.forename: S
authors.initials: S
authors.lastname: Shenoy
authors.forename: W J
authors.initials: WJ
authors.lastname: Grossman
authors.forename: J
authors.initials: J
authors.lastname: DiPersio
authors.forename: L C
authors.initials: LC
authors.lastname: Yu
authors.forename: D
authors.initials: D
authors.lastname: Wilson
authors.forename: Y J
authors.initials: YJ
authors.lastname: Barnes
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
authors.forename: A
authors.initials: A
authors.lastname: Rao
authors.forename: R J
authors.initials: RJ
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006402:Hematologic Diseases / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007223:Infant; D008206:Lymphatic Diseases / Q000628:therapy; D008297:Male; D008661:Metabolism, Inborn Errors / Q000628:therapy; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents