Immunosuppressive therapy for severe aplastic anemia in children under the age of 3 years yields a high response rate: a North American collaborative study

Abstract

Distinguishing acquired (idiopathic/immune) severe aplastic anemia (SAA) from inherited bone marrow failure syndromes (IBMFS) is critical since only acquired cases respond to immunosuppressive therapy (IST), the standard treatment in cases without a matched sibling donor. Differentiating SAA from IBMFS is particularly challenging in children younger than 3 years, in whom inherited disorders are more prevalent. No age threshold exists to guide IST use in this population. Thus, we evaluated IST outcomes in children aged <3 years, diagnosed with acquired SAA across three registries: North American Pediatric Aplastic Anemia Consortium, Canadian Aplastic Anemia and Myelodysplasia Study, and Canadian Inherited Marrow Failure Registry. Patients with suspected IBMFS based on clinical assessment, first-degree family history of marrow failure, or insufficient data were excluded.

Among 30 patients aged 15.6-34.8 months at diagnosis, 93% received horse anti-thymocyte globulin and cyclosporine A (CSA); 80% ultimately achieved complete response (CR). Median CSA duration among responders was 20.4 months (range, 5.6-55). By 4, 6, and 12 months, 50%, 92%, and 100% of responders were transfusion-independent. Once achieved, CRs were durable, with no relapses during a median 56-month follow-up after CSA cessation. Six patients (20%) did not respond: five underwent hematopoietic stem cell transplantation; one achieved CR to second IST after an initial partial response and transition to danazol. Complications included infections, bleeding, hypertension, gingival hypertrophy, and chronic kidney disease. No deaths occurred during follow-up (median, 73 months). In conclusion, these findings highlight, for the first time, strong IST efficacy in children aged 1.3-<3 years with acquired SAA.