Outcomes in Children with Severe Aplastic Anemia Receiving Bone Marrow Transplantation from an HLA-Matched Family Donor or Intensive Immunosuppressive Therapy As First-Line Treatment,

Abstract 3421

Bone marrow transplantation (BMT) from an HLA-matched family donor (MFD) is the treatment of choice for severe aplastic anemia (SAA) in children. For children without an MFD, immunosuppressive therapy (IST) with a combination of antithymocyte globulin and cyclosporine has been successful. However, this treatment approach is based on the results of comparative studies between these therapies conducted in the 1980s, and the outcomes of both BMT and IST have improved markedly over the past three decades. Therefore, updated evidence for treatment decisions in pediatric SAA is required. In the present study, we compared the outcomes of children with SAA who received IST (subjects enrolled in the prospective multicenter trials of IST conducted by the Japan Childhood Aplastic Anemia Study Group) or BMT from an MFD (subjects registered in the Transplant Registry Unified Management Program conducted by the Japan Society for Hematopoietic Cell Transplantation). The influence of potential risk factors on overall survival (OS) and failure-free survival (FFS) was assessed according to first-line treatment, time period of treatment (1992–1999 and 2000–2009), age and other variables related to each treatment. FFS was defined as survival with treatment response. Death, primary or secondary graft failure, relapse and secondary malignancy were considered treatment failures in patients who received BMT. Death, relapse, disease progression requiring stem cell transplantation from an alternative donor or 2nd IST, clonal evolution and evolution to paroxysmal nocturnal hemoglobinuria were considered treatment failures in patients who received IST. Between 1992 and 2009, 599 children with SAA younger than 17 years received BMT from an MFD (n=213) or IST (n=386) as first-line treatment. While the OS did not differ between patients receiving IST and BMT (88±2% vs. 90±2% at 15 years), FFS was significantly inferior in patients receiving IST as compared to those receiving BMT (54±3% vs. 84±3% at 15 years, P<0.0001). There was no significant improvement in outcomes over the two time periods; OS and FFS at 10 years in 1992–1999 vs. 2000–2009 were 87±2% vs. 93±2% and 66±3% vs. 67±3%, respectively. On multivariate analysis, age <10 years was identified as a favorable factor for OS (P=0.007) and choice of first-line IST was the only unfavorable factor for FFS (P<0.0001). These updated data support the current algorithm for treatment decisions, which recommends BMT when an MFD is available.