title: Mixed chimerism and graft loss in pediatric recipients of an alemtuzumab-based reduced-intensity conditioning regimen for non-malignant disease.
abstract: BACKGROUND
  Reduced-intensity conditioning (RIC) regimens can mitigate the toxicity of hematopoietic cell transplantation (HCT) in children with non-malignant diseases, but are associated with increased risk for post-transplant mixed donor/recipient chimerism (MC) and/or graft loss (GL). Intervention with donor lymphocytes or stem cell boosts (DLI/boost) may be necessary, but there is limited information about timing and results of intervention.
  
  
  METHODS
  We retrospectively evaluated 31 consecutive pediatric recipients of an alemtuzumab-based RIC HCT at the Children's Hospital of Philadelphia from May 2007 to December 2012 to determine the incidence of MC, GL, and use of DLI/boost. All patients received alemtuzumab with either fludarabine (150 mg/m(2) )/melphalan (140 mg/m(2) ) (n = 30) or fludarabine/busulfan (n = 1), and unmanipulated marrow grafts from related (48%) or matched unrelated (52%) donors.
  
  
  RESULTS
  Of surviving patients, 67% and 44% displayed MC and MC with ≤80% donor contribution (MC ≤ 80%), respectively. Rates of MC, MC ≤ 80%, DLI/boost, and GL were significantly higher in recipients of proximal/intermediate (100%, 73%, 46%, and 46%, respectively) compared to distal alemtuzumab (44%, 25%, 6%, and 6%, respectively). Event-free and overall survival was significantly lower in HLH compared with non-HLH patients. Twenty percent of patients required DLI/boost, and DLI/boost did not affect the incidence of GL.
  
  
  CONCLUSIONS
  RIC with proximal/intermediate alemtuzumab is associated with high rates of MC, need for DLI/boost, and GL.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Oshrine
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Olson
authors.forename: Nancy
authors.initials: N
authors.lastname: Bunin
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D012189:Retrospective Studies; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab
keywords: CAMPATH; alemtuzumab; bone marrow transplant; non-malignant disease; reduced-intensity conditioning