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


METHODS
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.
Savage
William J
WJ
Department of Pediatric Oncology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
DeRusso
Patricia A
PA
Resar
Linda M
LM
Chen
Allen R
AR
Higman
Meghan A
MA
Loeb
David M
DM
Jones
Richard J
RJ
Brodsky
Robert A
RA
D000293:Adolescent; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011446:Prospective Studies; D012074:Remission Induction; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide