title: Comparative Toxicity by Sex Among Children Treated for Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group.
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.
  
  
  METHODS
  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.
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Meeske
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ji
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: David R
authors.initials: DR
authors.lastname: Freyer
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Gaynon
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ruccione
authors.affiliation: Agensys, Inc., Santa Monica, California.
authors.forename: Anna
authors.initials: A
authors.lastname: Butturini
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Vassilios I
authors.initials: VI
authors.lastname: Avramis
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Stuart
authors.initials: S
authors.lastname: Siegel
authors.affiliation: Division of Hematology-Oncology, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Yousif
authors.initials: Y
authors.lastname: Matloub
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland.
authors.forename: Nita L
authors.initials: NL
authors.lastname: Seibel
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California.|Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000628:therapy*; D012189:Retrospective Studies; D012727:Sex Characteristics; D015996:Survival Rate
keywords: acute lymphoblastic leukemia; acute toxicities; disparities; pediatric oncology; sex