Improving the outcomes of young Black adults diagnosed with acute myeloid leukemia
Ann-Kathrin Eisfeld
MDThe Ohio State University
Project Term: October 1, 2021 - September 30, 2024
Young Black patients diagnosed with acute myeloid leukemia (AML) have significantly shorter survival compared to White patients. To comprehensively assess genetic, genomic and biologic contributors to the race-associated survival disparity, we propose a complementary approach that addresses major knowledge gaps in our current understanding of AML biology in Black patients, including the overdue characterization of the Black AML genome and subsequent delineation of biologic response to treatment.
Acute myeloid leukemia (AML) is an aggressive blood cancer affecting ~20,000 Americans each year. While being diagnosed with AML is still only associated with long-term survival rates of ~40% of younger and ~15% of older adults, due to recent advances in our understanding of the underlying molecular underpinnings of AML the outcomes of especially young patients with AML are constantly improving. However, we recently conducted the thus far largest study to specifically analyze the survival of Black patients diagnosed with AML. Our data showed that Black patients did not benefit from scientific advances over the past decades to the same degree as White patients, and that especially young Black patients have a 40% higher chance of dying from leukemia than Whites. Notably, this survival disparity was especially pronounced in young patients classified as "favorable risk" based on current guidelines. We also showed that common alterations in leukemia genes occur in different frequencies and have different survival impact in Black compared to White patients. This is not surprising, since all large studies to understand AML on a molecular level have almost exclusively been conducted on White patients. Thus, we hypothesize that the current lack of understanding of the underlying molecular underpinnings and, consequently, disease biology contributes to the poor disease outcomes of young, Black patients diagnosed with AML. Our proposal is designed to comprehensively address this disparity. In Aim 1, we will fully characterize genes involved in AML of young "favorable risk" Black patients, including gene mutations, and associated changes in signaling pathways that help us understand leukemia cell growth. With completion of Aim 1 we will for the first time be able to consider genes that are important in AML of Black patients in the same manner as we do for White patients. In Aim 2, we will use a mouse model to assess whether different types or strength of chemotherapy are needed to eradicate leukemic cells in Black patients. Furthermore, we will test in a large set of longitudinally collected samples of Black AML patients whether small numbers of leukemic cells persist with current therapeutic measures, and eventually cause the frequent disease recurrence observed in those patients. With completion of Aim 2 we will have delineated which treatment kind and strength is best suited to treat AML in young, Black AML patients. In addition, we will have determined whether routine assessment of measurable residual disease either via standard testing versus use of a novel ultra-sensitive method may help identify patients that require additional therapy to successfully treat their leukemia. In sum, we are hopeful that this long-overdue determination of the underlying disease biology of AML in Black patients will enable risk-adapted, personalized treatment strategies for every person diagnosed with AML, and reduce the unacceptable, race-associated survival disparity.