High-dose cyclophosphamide treatment for refractory severe aplastic anemia in children.

Objective: To determine if high-dose cyclophosphamide is an effective therapy for children with refractory severe aplastic anemia (SAA).

Background: SAA is an illness characterized by the depletion of hematopoietic precursors associated with life-threatening complications. Hematopoietic stem cell transplant (HSCT) is the treatment of choice if a human leukocyte antigen (HLA)-related donor is available. Immunosuppression with anti-thymocyte globulin (ATG) and cyclosporine A (CSA) is an option for patients who are not HSCT candidates. Unrelated donor HSCT has been used with limited success. High-dose cyclophosphamide has been used successfully in the treatment of adults with SAA, but experience in children is limited.

Procedure: Five pediatric patients who had failed previous immunosuppressive therapy for SAA were treated with high-dose cyclophosphamide (45 mg/kg/day x 4 days).

Results: After 12 months of treatment, two of five patients experienced a complete response with high-dose cyclophosphamide therapy. The two complete responders achieved red cell recovery with a hematocrit of >36% at days 212 and 112 and platelet recovery with a platelet count of >100 x 10(9)/L at days 126 and 324. Of the remaining patients, one patient failed to respond, and two patients expired from infectious complications.

Conclusions: High-dose cyclophosphamide can lead to complete responses in children with SAA who have failed to respond to traditional immunosuppressive therapy.