Currently aplastic anemia is treated with immunosuppressive therapy (IST) or a bone marrow transplant. Approximately 30% of aplastic anemia patients treated with IST are refractory to treatment or develop myelodysplastic syndromes (MDS) and leukemia. Tests to predict which patients will fare poorly to immunosuppressive therapy would inform upfront treatment decisions. We will utilize cutting edge genomic technologies to screen for genetic markers predictive of poor outcomes with IST. This study will develop a novel diagnostic tool for aplastic anemia to guide treatment decisions with the goal of improving patient survival.
Project Title: Genetic predictors of response to immunosuppressive therapy for aplastic anemia
Currently, aplastic anemia is treated with immunosuppressive therapy (IST) or a bone marrow transplant.
Approximately 30% of aplastic anemia patients treated with IST are refractory to treatment or develop myelodysplastic syndrome (MDS) and leukemia. Tests to predict which patients will fare poorly with immunosuppressive therapy would inform upfront treatment decisions. We are utilizing cutting edge genomics technologies to screen for genetic markers predictive of poor outcomes with IST. This study will develop a novel diagnostic tool for aplastic anemia to guide treatment decisions with the goal of improving patient survival. In the first year of this study we have completed our retrospective chart review for analysis of clinical outcomes and performed genetic sequencing for 94 pediatric and young adult patients with aplastic anemia. Analysis of the genetic data is ongoing. Early results have already identified pathogenic mutations and validation studies are in progress. The study has also been extended to include children and young adults with MDS.
Currently, aplastic anemia is treated with immunosuppressive therapy or a bone marrow transplant. Approximately 30% of aplastic anemia patients treated with immunosuppressive therapy are refractory to treatment and 10-15% develop myelodysplastic syndrome (MDS) or leukemia. Pediatric MDS is treated with a bone marrow transplant, but patients with genetic syndromes are at increased risk of transplant-related toxicities and post-transplant complications. Tests to predict which patients will fare poorly with immunosuppressive therapy or standard transplant regimens would inform upfront treatment decisions. We utilized cutting edge genomics technologies to screen for genetic markers predictive of poor outcomes with immunosuppressive therapy or bone marrow transplant. We found that a significant subset (5- 10%) of pediatric and young adult patients with bone marrow failure and MDS would benefit from broad genetic screening to inform treatment and medical management. This genetic panel is now available for clinical testing.