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Shai Shen-Orr, Tsila Zuckerman, Shlomit Yehudai-Reshef - IMM-AGE Metrics in BMT: Advancing Predictive Tools for Graft-versus-Host Disease Mitigation in AML patients

The immune system's role in health and disease is influenced by genetics and lifelong exposure to diverse stimuli, resulting in significant individual variability. However, this diversity is not integrated into bone marrow transplantation (BMT), a last-line treatment for Acute Myeloid Leukemia (AML) patients. We aim to address this critical gap by comprehensively analyzing the immune systems of BMT recipients and donors, with a particular emphasis on mitigating the risk of Graft-versus-Host Disease (GvHD).

Recent work from the She-Orr lab characterized the immune system of healthy adults tracked longitudinally for 9 years and identified a high-dimensional trajectory that approximates the changes an individual's immune system undergoes over time. One’s position on the trajectory, the IMM-AGE score, is assessed by measuring a weighted combination of 18 different immune cells from the peripheral blood. IMM-AGE was shown to have clinical predictive power.

The Zuckerman-Reshef laboratory investigates the bone marrow's environment and the role it plays in AML development. The laboratory's “know-how” is required to design the proposed study, work with samples from BMT recipients and donors, select appropriate patients, and analyze the clinical information.

Together, we tracked BMT donors and recipients - for 1 year post-transplantation by collecting blood and marrow aspirations. By leveraging the computational expertise of the Shen-Orr lab to explore the relevance of IMM-AGE in BMT in conjunction with Zuckerman-Reshef lab’s clinical insights, we believe we can provide physicians with a predictive tool for accurate patient-donor matching to reduce the risk of adverse outcome, particularly in GvHD.

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