FY20-Circulating Tumor DNA as a Prognostic Indicator of Minimal Residual Disease and Central Nervous System Relapse in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, and relapse or disease spread into the central nervous system have poor outcomes. ALL progression and response to therapy is monitored clinically by examining the patient’s blood, bone marrow, and spinal fluid for the presence of leukemia cells. Yet animal models of ALL, as well as sequencing data from patients, have shown that leukemia cells can remain at such low levels in the bone marrow or CNS that they would not be detected with clinical protocols, yet these cells will eventually cause bone marrow or CNS relapse. If clinicians knew that the cells were there, they could more aggressively treat the patient to prevent relapse, with either intensified chemotherapy or CAR-T immunotherapy. Leukemia cells, like all cancer cells, release pieces of their DNA into the patient’s bloodstream, called cell-free, circulating tumor DNA or ctDNA. Analysis of ctDNA from the patient’s blood has shown great promise in detecting relapse and metastasis in solid tumors, and has been used to analyze the clonal response to therapy in chronic lymphocytic leukemia, but has not yet been applied to ALL or CNS relapse in leukemia. The goal of our project is to determine the extent to which detection of ctDNA from ALL in patient blood and CNS samples can predict bone marrow or CNS relapse, and whether it can do so at an earlier time point than the current clinical assays that rely on the presence of cells within the sample. We want to develop a rapid, accurate test that doctors can use to determine the best treatment plan for their patients