Long-Term Clinical Outcome in Children with Very Severe Aplastic Anemia

Introduction: The clinical course of pediatric patients with severe aplastic anemia (SAA) treated with immunosuppressive therapy (IST) or hematopoietic cell transplantation (HCT) is well known. However, reports on the course and prognosis of patients with very severe aplastic anemia (vSAA) are few. Here, we report on the characteristics and outcome of children with vSAA.

Methods: We reviewed the medical records of patients diagnosed with vSAA at the Department of Pediatrics, St. Mary’s Hospital, The Catholic University of Korea between January, 1995 to December, 2007. We analyzed the clinical characteristics of the patients at diagnosis, and the effects of IST, HSCT and other supportive treatment measures on patient outcome.

Results: Forty three patients were diagnosed with vSAA during the study period, of whom 9 received supportive treatment measures only, 21 received IST consisting of cyclosporine A and either ATG or ALG, and 15 underwent HCT (including 2 patients who showed no response to initial IST). Of the 9 children who received supportive measures only, one patient recovered spontaneously and is surviving event-free for 22 months, 6 patients died from either severe infection or bleeding from 1 to 10 months after diagnosis (median 5 months), and the other two children are continuing to receive supportive transfusions. Of the patients with IST, two children showed a complete response (10.5%), 6 patients showed a partial response (31.6%), and eleven failed to respond (57.9%). Of the 11 patients who did not respond, 8 children died from infection or bleeding within 9 months after IST respectively, 2 patients were lost to follow-up, and 1 patient is receiving supportive transfusions. Of the 8 patients who showed a response, 2 have shown relapse and are being maintained with transfusions. Of the 15 HCT’s, 12 were from HLA-matched sibling donors and 3 were from matched unrelated donors. Except for the 2 patients who died from serious infections at 5 and 9 months post-HSCT respectively, all are currently surviving disease-free. The 10-year survival of the patients who received supportive measures only, IST, or HCT is 33.3±15.7%, 47.4±14.0 and 86.7±8.8% respectively (P=0.009).

Conclusion: As with SAA, HCT is the best treatment option for vSAA. If IST is undertaken, measures should be undertaken to prevent death from early infection. With only supportive care, median survival approximates only 6 months, calling for more intensive treatment strategies such as IST or HCT in the care of vSAA patients.