Telomere length is predictive for determining which children treated for acute myeloid leukemia (AML) are at highest risk for delayed recovery, a finding that may have significant implications for treatment-related morbidity and mortality. The length of a patient’s telomeres can indicate the rate of white blood cell recovery following chemotherapy treatment.1
“Telomeres are the protective caps on chromosome ends that keep DNA from fraying as you age, much like the plastic end of a shoelace prevents it from unraveling. We were interested in telomere length as a marker of blood count recovery because defects in telomere maintenance are known risks for bone marrow failure and aplastic anemia,” explained Maria Monica Gramatges, MD, PhD, assistant professor of pediatric oncology at Baylor College of Medicine, Houston, Texas.
Blood count recovery after a course of chemotherapy for AML can take 2 months or longer for up to 15% to 20% of children. “Our goal was to understand if these children had an underlying genetic predisposition associated with an impaired capacity for recovery,” said Gramatges.
The chemotherapy necessary to treat AML in children can be grueling on the body, and can cause health-related complications during therapy as well as after remission occurs. Children undergoing treatment for AML receive 4 to 5 intensive courses of chemotherapy, and although some children recover quickly from each course, recovery may take several months or more for others, which increases their risk for life-threatening infections.
The research team sought to test the hypothesis that short remission telomere length could be associated with a delay in blood count recovery in children undergoing treatment for AML. The researchers obtained remission bone marrow samples following the first chemotherapy course from patients with AML who recovered as expected (within 30 days) after each chemotherapy course, and from patients with AML who experienced significant delays after chemotherapy. Telomere length was measured on each participant and categorized by quartile, from shortest to longest.
Patients in the quartile with the shortest telomere lengths took the most time to recover, especially during the last 2 courses of chemotherapy, with some in that group not recovering at all.
These findings support the hypothesis that telomeres are an indicator of capacity for blood count recovery following chemotherapy treatment.
Gramatges hopes these results will further understanding of which children are at a higher risk for prolonged myelosuppression, and to target those children at the highest risk for slow recovery to receive modified treatments, improved supportive care, and closer monitoring to prevent potential complications such as severe infections.
“A significant proportion of children with AML suffer from treatment-related toxicities, with some succumbing to complications of the therapies we give, rather than from the actual cancer itself,” said Gramatges. “We hope this research will help us identify those who are at a higher risk for delayed recovery and use this knowledge to reduce the morbidity and mortality associated with AML treatment.”
1. Gerbing RB, Alonzo TA, Sung L, et al. Shorter remission telomere length predicts delayed neutrophil recovery after acute myeloid leukemia therapy: a report from the Children’s Oncology Group. J Clin Oncol. 2016 Jun 27. doi:10.1200/JCO.2016.66.9622. [Epub ahead of print]