Lack of Clinical Trial Participation and Shorter Duration of Therapy Linked to Disease Relapse in AYAs With Leukemia

Key Points

  • Children with ALL had superior relapse-free survival compared with AYAs with ALL.
  • Among these patients, the strongest predictors of relapse were race—nonwhite patients were twice as likely to relapse—and enrollment in clinical trials. Those who were not enrolled were 2.6 times more likely to relapse.
  • Following therapy completion, 47% of AYAs suffered a relapse, compared with 13% of children. Among these patients, the most significant factor was treatment duration, both in the consolidation and maintenance phases. For each additional month of maintenance therapy, there was a 30% lower risk of relapse.

Despite survival gains for children diagnosed with acute lymphoblastic leukemia (ALL), adolescents and young adults (AYAs)—those between the ages of 15 and 39—diagnosed with the disease have seen only modest improvements in survival. A study by Wolfson et al in Cancer Epidemiology, Biomarkers & Prevention investigating the disparity in survival outcomes of AYAs diagnosed with ALL compared with children with ALL has found that lower clinical trial enrollment and shorter duration of treatment are associated with relapse after completing therapy.

The study’s findings highlight the importance of clinical trial participation and the completion of therapy, both in the consolidation and maintenance phases. The study also found that other factors such as socioeconomic status and insurance status contributed to relapse in AYA patients.

Study Methodology

The study researchers assembled a retrospective cohort of patients with ALL diagnosed between ages 1 and 30 from 1990 to 2010, who had been diagnosed and/or treated at City of Hope in Duarte, California. The patient population consisted of 91 children (aged 1–14) and 93 AYAs (aged 15–39).

The researchers analyzed demographics from the patients’ medical records, including sex, age at diagnosis, race/ethnicity, insurance status, and socioeconomic status; whether the patients had been enrolled in a clinical trial; the duration of treatment; treatment approach; and oncology service, in which the researchers classified primary oncologists based on their treatment of patients on either pediatric or medical oncology services. Kaplan-Meier survival analysis was used to calculate relapse-free survival from diagnosis through relapse, death, or date of last contact.

Study Results

The researchers found that AYAs experienced an increased risk of on-therapy relapse vs children (hazard ratio [HR] = 10.5, P = .004). In multivariable analysis restricted to AYAs, independent predictors of relapse included lack of clinical trial enrollment (HR = 2.6, P = .04) and nonwhite race/ethnicity (HR = 2.2, P = .05).

When compared with children, AYAs experienced an increased risk of relapse after completing therapy (HR = 7.7, P < .001). In multivariable analysis restricted to AYAs, longer therapy (months of maintenance: HR = 0.7, P < .001; months of consolidation: HR = 0.8, P = .03) protected against relapse.

“Among AYAs, aspects of health-care delivery (clinical trial enrollment, nonwhite race/ethnicity) are associated with relapse during therapy, and aspects of treatment (shorter duration of maintenance and consolidation) are associated with relapse after completing therapy,” concluded the study authors.

Julie A. Wolfson, MD, MSHS, Assistant Professor and member of the Institute for Cancer Outcomes and Survivorship at the School of Medicine at the University of Alabama at Birmingham, is the corresponding author of this study.

Funding for this study was provided by the National Institutes of Health, the St. Baldrick’s Scholar Career Development Award, and the Concern Foundation. The study authors declared no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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