title: Outcomes of matched sibling donor hematopoietic stem cell transplantation for severe sickle cell disease with myeloablative conditioning and intermediate-dose of rabbit anti-thymocyte globulin.
abstract: BACKGROUND
  Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for sickle cell disease (SCD) in children. Despite excellent outcomes of matched sibling donor (MSD) HSCT, there is still 5-10% chance of rejection and transplant related mortality (TRM) with 12-23% incidence of graft versus host disease (GVHD). We postulated that an intermediate dose of rabbit anti-thymocyte globulin (r-ATG, 10 mg/kg cumulative) would be effective in preventing both rejection and GVHD.
  
  
  METHODS
  Fifteen patients, median age 5 (range 1.5-18) years, underwent MSD HSCT using busulfan (≥ 12.8 mg/kg with first dose pharmacokinetics), cyclophosphamide (total 200 mg/kg) and r-ATG. Bone marrow was the stem cell source; tacrolimus and methotrexate were given for GVHD prophylaxis.
  
  
  RESULTS
  All patients achieved donor engraftment and there was no TRM. One patient rejected donor cells at 2 months post-transplant. Majority of the patients had high and sustained level of donor chimerism. None of the patients developed ≥ Grade II GVHD. Incidence of CMV (10%) and EBV (9%) reactivations was low with rapid immune-reconstitution. Overall survival was 100% with event free survival of 93%.
  
  
  CONCLUSIONS
  Eliminating the risks of TRM and GVHD by optimizing the regimen may lead to further acceptance of HSCT for SCD.
authors.affiliation: Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Soni
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gross
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Rangarajan
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
authors.forename: Mollie
authors.initials: M
authors.lastname: Sturm
authors.forename: Melissa
authors.initials: M
authors.lastname: Rhodes
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000628:therapy*; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002066:Busulfan / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011446:Prospective Studies; D011817:Rabbits; D035781:Siblings; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D002066:Busulfan
keywords: blood and marrow transplant; sibling donor; sickle cell disease; stem cell transplant