title: Pilot trial of risk-adapted cyclophosphamide intensity based conditioning and HLA matched sibling and unrelated cord blood stem cell transplantation in newly diagnosed pediatric and adolescent recipients with acquired severe aplastic anemia.
abstract: BACKGROUND
  Cyclophosphamide-based conditioning regimens and allogeneic hematopoietic stem cell transplantation (AlloHSCT) from matched related donors (MRD) has resulted in the highest survival rates in children and adolescents with acquired severe aplastic anemia (SAA). Time to transplant has consistently been associated with decreased overall survival. Reduced toxicity conditioning and AlloHSCT has been used successfully in other pediatric non-malignant diseases.
  
  
  METHODS
  We piloted a risk-adapted AlloHSCT approach, using fludarabine and anti-thymocyte globulin based conditioning with high (200 mg/kg) and low (60 mg/kg) dose cyclophosphamide as upfront treatment in newly diagnosed pediatric patients with acquired SAA incorporating alternative donor sources, including cord blood. Average risk for non-engraftment patients with <10 transfusions received low dose cyclophosphamide (60 mg/kg); High Risk, those with ≥10 transfusions received conditioning regimen with higher intensity cyclophosphamide (200 mg/kg).
  
  
  RESULTS
  Seventeen patients were enrolled and underwent AlloHSCT including 12 males and 5 females with mean age of 8 years (range 3-16), and median follow-up time of 39 months (range 1-135). Donor sources included MRD BM (6/6 [n = 9], 5/6 [n = 2]) and unrelated CB (5/6 [n = 4], 4/6 [n = 2]). Five year OS was 67.6% (37.9-85.4). Three secondary graft failures (17.6%) occurred in the low dose cyclophosphamide arm.
  
  
  CONCLUSIONS
  Upfront treatment with risk-adapted cyclophosphamide conditioning AlloSCT is well tolerated for the management of newly diagnosed pediatric and adolescent patients with acquired SAA. However, the increased risk of graft rejection in the lower dose arm warrants additional research regarding the optimal intensity of cyclophosphamide-based conditioning regimen to reduce toxicity without increasing graft failure.
authors.affiliation: Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Catherine
authors.initials: C
authors.lastname: McGuinn
authors.forename: Mark B
authors.initials: MB
authors.lastname: Geyer
authors.forename: Zhezhen
authors.initials: Z
authors.lastname: Jin
authors.forename: James H
authors.initials: JH
authors.lastname: Garvin
authors.forename: Prakash
authors.initials: P
authors.lastname: Satwani
authors.forename: M Brigid
authors.initials: MB
authors.lastname: Bradley
authors.forename: Monica
authors.initials: M
authors.lastname: Bhatia
authors.forename: Diane
authors.initials: D
authors.lastname: George
authors.forename: Deirdre
authors.initials: D
authors.lastname: Duffy
authors.forename: Erin
authors.initials: E
authors.lastname: Morris
authors.forename: Carmella
authors.initials: C
authors.lastname: van de Ven
authors.forename: Joseph
authors.initials: J
authors.lastname: Schwartz
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000293:Adolescent; D064591:Allografts; D000741:Anemia, Aplastic / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D010865:Pilot Projects; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D019172:Transplantation Conditioning; D061349:Unrelated Donors
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: acquired severe aplastic anemia; adolescent; matched donors; pediatric; risk-adapted conditioning; unrelated donors