Simultaneous Monitoring of Disease and Microbe Dynamics Through Plasma DNA Sequencing in Pediatric Patients with Acute Lymphoblastic Leukemia

Treatment of acute lymphoblastic leukemia (ALL) necessitates continuous risk assessment of leukemic disease burden as well as infections that arise in the setting of immunosuppression and myelosuppression. This study was performed to assess the feasibility of a hybrid capture NGS panel to longitudinally measure molecular leukemic disease clearance and microbial species abundance in 20 pediatric patients with ALL throughout induction chemotherapy. This proof-of-concept helps establish a technical and conceptual framework that we anticipate will be expanded and applied to additional patients with leukemias, as well as extended to additional cancers. Molecular monitoring can help to accelerate the attainment of insights into the temporal biology of host-microbe-leukemia interactions, including how those changes correlate with and alter anticancer therapy efficacy. We also anticipate fewer invasive bone marrow aspirations or biopsies will be required as these methods improve with standardization and are validated for clinical use. Key Points A custom-designed hybridization capture next generation sequencing (NGS) panel noninvasively and quantitatively measures leukemic disease burden and microbial species abundance through serial peripheral blood draws throughout induction chemotherapy. Sequencing of circulating tumor DNA (ctDNA) alongside microbial cell free DNA (mcfDNA) in the same sample reveals the effectiveness of chemotherapy alongside the immunosuppressive consequences of cytotoxic therapy. Efforts to incorporate ctDNA and mcfDNA NGS monitoring in higher risk patient populations have the potential to uncover mechanisms of response, resistance, and infectious complications that correlate with patient outcomes.