A Registry and Sample Repository for Patients with Bone Marrow Failure Facilitates Research into Genetic Origins, Clonal Evolution to Cancer, and Prognostic Factors Affecting Treatment Outcome

Patients with Acquired and Inherited Bone Marrow Failure suffer from the inadequate production of blood cells, resulting in high infection risk, severe anemia, and bleeding complications.  While research over the last two decades has identified the underlying genetic cause of many bone marrow failure syndromes, the genetic predispositions leading to marrow failure in the majority of patients remains undefined. 

Additionally, 10-50% of patients with bone marrow failure, depending on the underlying subtype, will ultimately develop malignancies including leukemia. This classifies these bone marrow failure conditions as cancer predisposition syndromes.   

Researchers at the Center for Childhood Cancer Research (CCCR), in collaboration with Adult Hematologists at The University of Pennsylvania, have created a large bone marrow failure patient registry and sample repository that is continuing to enroll both adult and pediatric patients.

Blood, bone marrow, and skin samples are collected from patients seen in the Combined Pediatric-Adult Bone Marrow Failure Center. These samples are then used in studies to understand the molecular basis of these disorders and factors that influence progression to cancer. 

Ongoing studies are specifically investigating hematopoietic clonal evolution in patients with acquired bone marrow failure, also known as aplastic anemia (AA). Ten to 20% of patients with aplastic anemia not treated with curative stem cell transplantation will ultimately develop myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Using cutting edge genomic technologies such as Whole Exome Sequencing, Genome-Wide Array analyses, and the creation of screening Next Generation Sequencing Panels, researchers are beginning to identify common patterns of acquired mutations and chromosomal changes in patients with AA that may predict treatment response and risk of developing leukemia. 

One long-term goal of these studies is to create a genetic testing panel that includes all common predictive mutations that occur in patients with AA. This panel would be used to tailor individualized therapy strategies for patients and their families based on their unique genetic profile.