This study attempts to learn more about the health of persons with Down syndrome after treatment for acute leukemia. Children with Down syndrome are at increased risk for side effects during treatment for acute leukemia, but it is unclear of their risk for long-term effects of cancer treatment. By learning more about the factors that may contribute to chronic health conditions and long-term effects after treatment for leukemia in persons with Down syndrome, clinical practice guidelines for survivorship care can be developed to help improve their quality-of-life.
PRIMARY OBJECTIVE: I. To determine the prevalence, type, and severity of chronic health conditions (CHC) in survivors of Down syndrome-associated acute leukemia (DS-AL), and to compare CHC with frequency-matched DS individuals that have no cancer history. SECONDARY OBJECTIVES: I. To characterize post-treatment clinical outcomes of DS-AL by prospective, in-person assessment. II. To determine the prevalence and severity of parent-reported adverse neuropsychological (NP) outcomes in survivors of DS-AL, compared with frequency-matched DS individuals with no cancer history. III. To determine health-related quality of life (HRQOL) in survivors of DS-AL, compared with frequency-matched DS individuals with no cancer history. IV. To identify clinical risk determinants of CHC, NP, and clinical outcomes in survivors of DS-AL. V. To establish a well-annotated cohort of survivors of DS-AL and associated biobank as a resource for future investigations. EXPLORATORY OBJECTIVES: I. For DS-acute lymphoblastic leukemia (DS-ALL), test if structural birth defects and genetic associations with etiology extend to CHC. II. For DS-ALL, test if telomere length determined by polygenic risk score and telomere flow-fluorescence in situ hybridization (FISH) are associated with outcomes from in-person NP assessment. OUTLINE: Patients undergo an optional saliva/buccal swab in part 1 and clinical assessment in part 2 of the study. Patients with DS-ALL may then undergo blood sample collection and neurocognitive assessment in part 3 of the study.
Study Type
OBSERVATIONAL
Enrollment
330
Patients undergo saliva/buccal and blood sample collection
Undergo a clinical assessment
Undergo neurocognitive assessment
Ancillary studies
Ancillary studies
Children's Hospital of Alabama
Birmingham, Alabama, United States
RECRUITINGPhoenix Childrens Hospital
Phoenix, Arizona, United States
RECRUITINGValley Children's Hospital
Madera, California, United States
RECRUITINGUCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Prevalence, type, and severity of chronic health conditions (CHC)
Summary statistics will be used to characterize the study populations on CHC outcomes. Quantitative data (number of comorbidities) will be summarized using descriptive statistics and correlational techniques. Will use pooled logistic regression to estimate overall response, 95% confidence interval (CI), and p-values for association of acute leukemia (AL) diagnosis with medical record-verified CHC, agnostic of time to CHC. Will use stratified Cox models to refine associations of AL diagnosis with CHC based on time to CHC incidence. Within each age interval, will estimate the hazard ratio, 95% CI, and p-values to report time-dependent effects of AL diagnosis on CHC.
Time frame: Up to study completion
Post-treatment clinical outcomes
Summary statistics will be used to characterize the study population on clinical outcomes, by AL subtype and, for each test, the proportion of normal, abnormal, and missing tests.
Time frame: Up to study completion
Prevalence and severity of parent-proxy neuropsychological (NP) outcomes
NP outcomes (measured by both parent proxy and direct assessment) will be reported by both raw and normalized scores, and quantitative data summarized using descriptive statistics and correlational techniques. The mean score for each test will be compared between the cohorts using a student t-test (2-sided significance level of 0.05 and equal variance).
Time frame: Up to study completion
Health-related quality of life (HRQOL)
HRQOL will be assessed using the Pediatric Quality of Life Inventory. Parents will be asked to scale 23 items comprising four dimensions (Physical, Emotional, Social, and School functioning) on a 5 point unweighted Likert scale. Will use a t-test (or Wilcoxon rank sum test if appropriate) to compare the mean (or median) HRQOL score.
Time frame: Up to study completion
Clinical risk determinants of CHC, NP, and clinical outcomes
Will use Cox regression to estimate the hazard ratio and 95% CI for (1) number, severity, and type of CHC, and (2) NP deficits dichotomized as clinically significant impairment yes/no (=\< 1.5 standard deviation outside of the mean for the age-normative sample) according to age at diagnosis, years off therapy, sex, race/ethnicity, diagnosis, and treatment exposures.
Time frame: Up to study completion
Well-annotated cohort of Down syndrome phenotyping acute leukemia study (DS-PALS) survivors and associated biobank
The number of patients who agree to be in the Biobanking part of the study and have leftover tumor tissue and some normal blood, bone marrow, or other tissue saved for future research.
Time frame: Up to study completion
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Kaiser Permanente-Oakland
Oakland, California, United States
RECRUITINGUCSF Medical Center-Mission Bay
San Francisco, California, United States
RECRUITINGYale University
New Haven, Connecticut, United States
RECRUITINGAlfred I duPont Hospital for Children
Wilmington, Delaware, United States
RECRUITINGGolisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
RECRUITINGMemorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, United States
RECRUITING...and 58 more locations