title: Durable treatment-free remission after high-dose cyclophosphamide therapy for previously untreated severe aplastic anemia.
abstract: BACKGROUND
  Severe aplastic anemia is a life-threatening bone marrow failure disorder. High-dose cyclophosphamide therapy followed by allogeneic bone marrow transplantation cures the disease. However, it requires a suitable donor and carries the risk for graft-versus-host disease. A small pilot study demonstrated that high-dose cyclophosphamide therapy without bone marrow transplantation leads to durable, treatment-free complete remission.
  
  
  OBJECTIVE
  To confirm the safety and efficacy of high-dose cyclophosphamide therapy alone in patients with severe aplastic anemia.
  
  
  METHODS
  Uncontrolled clinical trial.
  
  
  METHODS
  Three tertiary care hospitals.
  
  
  METHODS
  19 patients with untreated severe aplastic anemia.
  
  
  METHODS
  Cyclophosphamide, 50 mg/kg of body weight per day for 4 consecutive days.
  
  
  METHODS
  Probability of response and overall survival were measured. Complete remission was defined as normal blood count for age and sex. Partial remission was defined as independence from transfusion and an absolute neutrophil count greater than 0.5 x 10(9) cells/L without growth factor support. Nonresponders were patients who remained transfusion dependent or died. Relapse was defined as no longer meeting criteria for partial or complete remission.
  
  
  RESULTS
  The median time to an absolute neutrophil count of 0.5 x 10(9) cells/L was 49 days. The probability of survival was 84% (95% CI, 59% to 95%) at 24 months. The probability of achieving treatment-free remission was 73% (CI, 51% to 91%) at 24 months, and the probability of achieving complete remission was 65% (CI, 39% to 89%) at 50 months. No responding patients have had relapse or have developed secondary clonal disorders.
  
  
  CONCLUSIONS
  High-dose cyclophosphamide therapy without bone marrow transplantation produces durable treatment-free remission in severe aplastic anemia. This approach deserves further study in patients with severe aplastic anemia who are not suitable candidates for allogeneic bone marrow transplantation.
authors.affiliation: Johns Hopkins Oncology Center, Bunting-Blaustein Cancer Research Building, Room 242, 1650 Orleans Street, Baltimore MD 21231, USA. rbrodsky@jhmi.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Brodsky
authors.forename: L L
authors.initials: LL
authors.lastname: Sensenbrenner
authors.forename: B D
authors.initials: BD
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Dorr
authors.forename: P J
authors.initials: PJ
authors.lastname: Seaman
authors.forename: S M
authors.initials: SM
authors.lastname: Lee
authors.forename: J E
authors.initials: JE
authors.lastname: Karp
authors.forename: I
authors.initials: I
authors.lastname: Brodsky
authors.forename: R J
authors.initials: RJ
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000932:Antiemetics / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D017294:Ondansetron / Q000627:therapeutic use; D010865:Pilot Projects; D017713:Platelet Transfusion; D011446:Prospective Studies; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D000932:Antiemetics; D007166:Immunosuppressive Agents; D017294:Ondansetron; D003520:Cyclophosphamide