Comparative Toxicity by Sex Among Children Treated for Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

Pediatr Blood Cancer. 2015 Dec;62(12):2140-9. doi: 10.1002/pbc.25628. Epub 2015 Jul 14.

Abstract

Background: Epidemiologic studies find sex-based differences in incidence, survival, and long-term outcomes for children with cancer. The purpose of this study was to determine whether male and female patients differ with regard to acute treatment-related toxicities.

Procedures: We reviewed data collected on the Children's cancer group (CCG) high-risk acute lymphoblastic leukemia (ALL-HR) study (CCG-1961), and compared male and female patients' toxicity incidence and related variables in the first four phases of treatment. Similar analyses were performed with standard-risk ALL (ALL-SR) patients enrolled in CCG-1991.

Results: Among ALL-HR patients, females had significantly more hospital days, delays in therapy, grade 3 or 4 toxicities (e.g., gastrointestinal, liver), and supportive care interventions (e.g., transfusions, intravenous antibiotics) than males. Females were significantly more likely to have died of treatment-related causes than males (Hazard ratio = 2.8, 95%CI = 1.5-5.3, P = 0.002). Five months after beginning the treatment, the cumulative incidence of treatment-related deaths was 2.6% for females and 1.2% for males. Similar disparities were found among ALL-SR patients, with females experiencing significantly more hospital days and treatment-related toxicities than males.

Conclusions: This study complements cancer survivorship studies that also report an increase in treatment-related late effects among females. Risk profiles appear to be different for male and female patients, with females having greater risk of developing both acute and long-term treatment-related toxicities. The underlying biological mechanisms for these sex differences are poorly understood and warrant further study in order to determine how sex-based outcome disparities can be addressed in future clinical trials and practice.

Keywords: acute lymphoblastic leukemia; acute toxicities; disparities; pediatric oncology; sex.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Retrospective Studies
  • Sex Characteristics*
  • Survival Rate