New research published by Larkin et al in the journal Blood Advances has found that Black adolescent and young adult (AYA) patients with acute myeloid leukemia (AML) were five times more likely than comparable White patients to die within 30 days of beginning treatment—and were twice as likely to die within 5 years, despite receiving similar treatment.

We found that among young Black and White patients who received similar intensive therapy on clinical trials, outcomes were dramatically inferior for Black patients compared with White patients—and this disparity occurred predominantly among patients aged 18 to 29 years.

— Karilyn Larkin, MD

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“To our knowledge, this is the first study to examine how molecular genetic alterations contribute to outcomes in young Black people with AML compared with their White counterparts,” said first and lead study author Karilyn Larkin, MD, a hematologist at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. “We found that among young Black and White patients who received similar intensive therapy on clinical trials, outcomes were dramatically inferior for Black patients compared with White patients—and this disparity occurred predominantly among patients aged 18 to 29 years.”

More on AML, Genetics, and Therapies for the Disease

Most people with AML receive their diagnosis within a few weeks after developing symptoms. Because the disease progresses rapidly, doctors traditionally advise most of their patients to start chemotherapy immediately—often within days of diagnosis.

Decades of research have generated a body of knowledge about the influence of many acquired genetic variants­, including changes in structural chromosomes as well as mutations in specific genes, on the risk for relapse and death in patients with AML, Dr. Larkin said. However, most of the data come from patients of European ancestry. Because Black patients continue to be underrepresented in cancer clinical trials, there remain critical gaps in knowledge. Understanding how these disease-specific genetic variants, which are acquired during a lifetime, differ between patients can help doctors identify effective treatment options on an individual or population basis.

The study also identifies clear differences in pretreatment molecular genetic profiles between young Black and White Americans with AML that may contribute to these widely varying outcomes and urgently need further study. The study did not address how structural racism and health-care disparities may contribute to different outcomes among Black patients with AML.

“From a genetic perspective, we are underserving these patients, on top of all of the other health-care inequities this historically underserved population faces,” Dr. Larkin said.

Study Details

For this study, Dr. Larkin and her colleagues analyzed data for 566 White and 89 Black patients between the ages of 18 and 39 with newly diagnosed AML who were treated in clinical trials run by the National Cancer Institute–supported research group (now known as the Alliance) between 1983 and 2016. The proportions of Black patients enrolled closely matched that of the general U.S. population, Dr. Larkin explained. The researchers also performed cytogenetic and molecular analyses of bone marrow and blood cell specimens that were collected from the patients before they were treated and after achieving remission. Samples were then stored for future research use.

They found that, among all the Black participants, 11% died within 30 days of beginning treatment, compared with 2% of White participants. Five-year survival was 32% for Black patients compared with 46% for White patients. Among Black patients between the ages of 18 and 29 years, the rate of early death was 16%, compared with only 3% for White patients in the same age group. Black patients in this age group survived for a median of just 1.3 years compared with a median of 10.2 years for White patients aged 18 to 29. In contrast, among patients in the 30- to 39-year age group, there were no significant differences in survival between Black and White participants.

Among people with a type of AML known as core-binding factor AML, Black patients had a higher rate of early death (12% vs 3%) and shorter 5-year survival (54% vs 70%) compared with White patients. The researchers could not identify any obvious clinical differences in pretreatment characteristics between the two groups to explain the Black patients’ higher rate of early death.

Why the Disparity?

Explanations for the high rates of early death among Black people with AML may include treatment delays or suboptimal care (which may reflect historical cultural biases and structural racism), other existing health conditions, or more aggressive disease, Dr. Larkin said. “Our findings support the need for additional prospective studies of Black young adult patients with AML to identify the reasons driving poor outcomes, as well as for heightened monitoring of individual Black patients being treated for AML today,” she said. “They also raise the question of why these young patients, who we would assume are healthy enough to tolerate intensive therapy, don't survive.”

Although the answers are beyond the scope of this study, Dr. Larkin said it could be related to more advanced disease at presentation; an imbalance of other medical conditions that could potentially affect tolerability of intense chemotherapy among our patients; increased susceptibility to negative effects of chemotherapy; or implicit bias affecting the care of these patients. She added that further study is needed.

A limitation of the study is a small number of records that omitted information about patient demographics and causes of early death precluded additional analysis that might have helped to explain the health outcomes inequities identified. Further study is needed to investigate the other social, environmental, and economic factors, aside from genetic differences, that may contribute to poorer outcomes among Black patients with AML.

Disclosure: For full disclosures of the study authors, visit ashpublications.org/bloodadvances.