Subset of Latino children with acute lymphoblastic leukemia may have higher relapse risk
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Among children diagnosed with acute lymphoblastic leukemia, Latinos without minimal residual disease had a higher likelihood of relapse than their white counterparts, according to study results.
Researchers reported the findings at American Association for Cancer Research Annual Meeting.
“Several studies have indicated that Latinos have worse outcomes compared with non-Latino whites, so trying to understand when during therapy that disparity begins was key to this assessment,” Philip J. Lupo, PhD, MPH, professor of pediatrics at Baylor College of Medicine and director of the epidemiology and population sciences program at Texas Children’s Cancer and Hematology Center, told Healio. “Additionally, there have been few assessments of relapse in contemporary multiethnic populations. It is critical to understand risk factors for relapse in these individuals.”
Background and methodology
The study included 1,662 children (> 60% Latino) diagnosed with ALL between 2004 and 2018 from the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, which comprises seven major pediatric cancer centers in the southwestern United States. About one-quarter of patients had minimal residual disease (MRD)-positive status.
Researchers defined time to relapse as time from ALL diagnosis to the initial relapse event. They censored patients at date of death, last follow-up or bone marrow transplant.
Clinical factors Lupo and colleagues evaluated included race/ethnicity, sex, age at diagnosis (1-5, 6-10, 11-15, > 15 years), ALL immunophenotype (B-cell, T-cell), NCI risk group, central nervous system involvement, enrollment on a Children’s Oncology Group clinical trial, end-induction disease failure, and end-induction bone marrow flow cytometric MRD.
Key findings
Results showed 237 (14.3%) experienced relapse, and 63% of those who relapsed had MRD-negative status.
An analysis of cumulative incidence of relapse by MRD status showed a higher proportion of children with MRD positivity relapsed compared with children with MRD negativity (22.9% vs. 11.5%).
Factors associated with relapse included MRD-positive status (adjusted HR [aHR] = 1.59; 95% CI, 1.11-2.29), race/ethnicity (Latino vs. white, aHR = 1.43; 95% CI, 0.9-2.29; Black vs. white, aHR = 1.4; 95% CI, 0.67-2.93), older age at diagnosis (15 years or older vs. 1-4 years, aHR = 3.13; 95% CI, 1.81-5.43) and unfavorable vs. favorable cytogenetics (aHR = 3.05; 95% CI, 1.74-5.33).
Among children with MRD-positive status, Latino children appeared less likely to relapse than white children in analyses adjusted for patient-level factors (aHR = 0.77; 95% CI, 0.45-1.32) and patient- and neighborhood-level factors (aHR = 0.89, 95% CI, 0.39-4.65). However, among those with MRD-negative status, Latinos had a higher risk for relapse in the patient-level (aHR = 1.61; 95% CI, 1.03-2.52) and patient- and neighborhood-level (aHR = 2.05; 95% CI, 1.11-3.76) adjusted analyses.
“Interestingly, while minimal residual disease is one of the strongest risk factors for relapse in the overall population, it did not predict relapse in Latino patients after accounting for other clinical and sociodemographic factors,” Lupo said. “In fact, we found that Latino patients who were negative for minimal residual disease were more likely to relapse. Clinically, this could influence risk stratification protocols for these children.”
Implications
Researchers noted that study limitations included they did not have complete information on all the factors that could have influenced relapse risk. In continuing the research, they plan to incorporate other critical factors into predictive models for ALL outcomes, with the ultimate goal, Lupo said, of eliminating disparities in outcomes among those diagnosed with ALL.
“It is important to evaluate the epidemiology and biology of relapse in Latino patients, which could improve risk stratification protocols for these individuals. And we must consider the impact of social determinants on these outcomes — clinical trials do not typically account for these factors,” Lupo said.
References:
Sok P, et al. Abstract 3633. Presented at American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans.
Some Latino children diagnosed with acute lymphoblastic leukemia face higher risk of relapse compared to non-Latino white children. at: https://www.aacr.org/about-the-aacr/newsroom/news-releases/some-latino-children-diagnosed-with-acute-lymphoblastic-leukemia-face-higher-risk-of-relapse-compared-to-non-latino-white-children/. Published April 12, 2022. Accessed April 12, 2022.
Perspective
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Kayleen A. Bailey, MD, MPH
For decades in pediatric oncology, we have known that underrepresented minorities have worse outcomes. Because of our overall small number of patients, we rely on retrospective studies such as this one to guide future research. As ALL is generally one of our most curable diseases, we must decode among the smaller subset of patients with refractory/relapsed disease to try to predict who will not fare well.
It is fascinating to me to learn of the strong role that ethnicity plays in differentiating which patients who are MRD-negative at the end of induction potentially would relapse. The conclusion that patients enrolled on a therapeutic clinical trial for ALL were less likely to relapse highlights the importance of making sure that all patients are offered a clinical trial if available at the time of diagnosis, a finding that has been supported in the literature. Unfortunately, based on the retrospective nature of the study, there are no formal recommendations to be made at this time to change practice guidelines for surveillance screening of Latino patients who are MRD-negative at end of induction. Although not a direct result of this study, in childhood ALL, practitioners have an important role in ensuring oral medication compliance throughout years 1 to 3 of ALL treatment to prevent relapse; perhaps we need to develop new strategies for patients who are already at risk due to ethnic differences.
This study puts a call out to researchers to examine the underlying differences — for example genetic underpinnings or drug pharmacokinetic differences — that could explain the disparity in response among Latino patients. Considering this research was conducted among six major cancer consortiums with clinical trial availability, I would be curious to know the number of patients treated in an underserved area that did not have access to a clinical trial. Although compliance with medications likely did not play a role in this study, as children generally are inpatients during induction, ALL treatment requires much buy-in from families to take oral chemotherapy at home for several years, and I wonder if there are differences in medication compliance between ethnic groups.
It would be prudent to power future prospective clinical trials to allow for examination of these disparities, with risk stratification and earlier escalation of therapy in at-risk groups, such as Latino.
Collapse
Sok P, et al. Abstract 3633. Presented at American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans.
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