title: High-dose Cyclophosphamide is Effective Therapy for Pediatric Severe Aplastic Anemia.
abstract: Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicity as compared with antithymocyte globulin and cyclosporine A. As children often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamide as the sole form of immunosuppression.
  
  
  
  Children and adolescents with SAA who lacked an human leukocyte antigen-matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis.
  
  
  
  Overall survival was 85%, with hematologic response of 79% and complete response of 66%. Cumulative incidences of bacterial infection (86%) and fungal infection (62%) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28).
  
  
  
  Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.
authors.affiliation: Departments of *Oncology, Division of Pediatric Oncology †Pediatrics, The Division of Hematology ‡Medicine, The Division of Hematology §Pathology, The Division of Transfusion Medicine ¶The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD ∥Department of Pathology and Lab Medicine, The Division of Transfusion Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gamper
authors.forename: Clifford M
authors.initials: CM
authors.lastname: Takemoto
authors.forename: Allen R
authors.initials: AR
authors.lastname: Chen
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Symons
authors.forename: David M
authors.initials: DM
authors.lastname: Loeb
authors.forename: James F
authors.initials: JF
authors.lastname: Casella
authors.forename: Amy E
authors.initials: AE
authors.lastname: Dezern
authors.forename: Karen E
authors.initials: KE
authors.lastname: King
authors.forename: Andrea M
authors.initials: AM
authors.lastname: McGonigle
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D060965:Clonal Evolution; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000633:toxicity; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007239:Infections / Q000139:chemically induced; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide