Shorter Remission Telomere Length Associated With Prolonged Neutropenia After Pediatric AML Treatment

Key Points

  • Shorter telomere length after induction therapy was associated with prolonged time to neutrophil recovery during intensification in pediatric patients receiving chemotherapy for AML.
  • The association remained after adjustment for age.

In a study reported in the Journal of Clinical Oncology, Gerbing et al found that prolonged posttreatment neutropenia was associated with shorter chromosomal telomere length in pediatric patients receiving chemotherapy for acute myeloid leukemia (AML).

Study Details

The study included 53 patients with and 62 patients without significantly delayed neutrophil recovery after chemotherapy for de novo AML in a Children’s Oncology Group study (AAML0531). Quantitative polymerase chain reaction was used to measure telomere content, a proxy for telomere length, from remission bone marrow samples after the second induction chemotherapy course.

Findings

Less telomere content was significantly associated with prolonged neutropenia after the fourth (P < .001) and fifth (P = .002) chemotherapy courses (second and third intensifications). For example, the mean time to neutrophil recovery after the second intensification was 53.8 days (range = 27–90 days) among patients with telomere content in the lowest quartile (Q1) compared with 42.7 days (range = 20–91 days) among those with telomere content in Q2 to Q4 (P = .021).  Telomere content remained independently predictive of prolonged time to neutrophil recovery for the fourth (P = .002) and fifth courses (P = .009) after analysis adjusting for age at diagnosis.

Analysis of DNA for germline mutations in four telomere maintenance genes associated with telomere biology disorders showed no enrichment for rare or novel variants in patients with delayed neutrophil recovery.

The investigators concluded: “Our results suggest that [telomere content] at [the] end of AML induction is associated with hematopoietic reconstitution capacity independently of age and may identify those at highest risk for markedly delayed bone marrow recovery after AML therapy.”

The study was supported by the Alex’s Lemonade Stand Young Investigator Award, St Baldrick’s Foundation, and the National Institutes of Health.

Maria M. Gramatges, MD, PhD, of Baylor College of Medicine, is the corresponding author of the Journal of Clinical Oncology article.

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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