Treatment of hepatitis-associated aplastic anemia with high-dose cyclophosphamide

Pediatr Blood Cancer. 2007 Dec;49(7):947-51. doi: 10.1002/pbc.21143.

Abstract

Objective: Demonstrate that high-dose cyclophosphamide (CY) is effective therapy for hepatitis-associated aplastic anemia (HAA).

Background: HAA is a sequence of seronegative hepatitis followed by aplastic anemia. Optimal treatment is matched-sibling allogeneic bone marrow transplantation (BMT). The combination of antithymocyte globulin (ATG) and cyclosporine (CSA) has also been studied, but there are scarce data regarding treatment of HAA.

Procedure: Five patients (median age 14 years; range 6-17 years) with HAA and without an HLA-matched sibling were treated with high-dose CY (50 mg/kg/day IV x 4 days) followed by granulocyte-colony stimulation factor (G-CSF).

Results: After at least 1 year of follow-up, four of five patients are in remission without further immune suppression beyond high-dose CY. Of the 4 responders, median time to absolute neutrophil count (ANC) >500 microl(-1) was 51 days (range 44-369). Median time to transfusion independence for erythrocytes and platelets was 109 (range 57-679) and 160 (range 48-679) days, respectively. The fifth patient did not respond and proceeded to an unrelated donor transplant. One patient met criteria for autoimmune hepatitis (AIH) in addition to HAA. In this case, high-dose CY successfully induced remission of both diseases.

Conclusions: High-dose CY induces durable remissions in HAA and may be an effective treatment for AIH.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Anemia, Aplastic / drug therapy*
  • Anemia, Aplastic / etiology
  • Anemia, Aplastic / pathology
  • Child
  • Cyclophosphamide / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hepatitis, Viral, Human / complications
  • Hepatitis, Viral, Human / drug therapy*
  • Hepatitis, Viral, Human / pathology
  • Humans
  • Infusions, Intravenous
  • Male
  • Prospective Studies
  • Remission Induction
  • Treatment Outcome

Substances

  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide