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.
Patients age >= 6 and < 40 years at the time of enrollment
A diagnosis of Down syndrome is required, and may include any of the three recognized types: trisomy 21 resulting from chromosomal nondisjunction (most common), translocation (the patient has 46 chromosomes, but all or part of an additional copy of chromosome 21 is attached to another chromosome), or mosaicism (trisomy 21 that is present in only a fraction of cells)
All patients must be DS-AL survivors (acute lymphoblastic leukemia [ALL] or acute myeloid leukemia [AML])
Note 1: Myeloid leukemia of Down syndrome (ML-DS) is included in the AML category above. Per the World Health Organization (WHO) definition of ML-DS, this diagnosis encompasses both myelodysplastic syndrome (MDS) and overt AML. Also, note that survivors of relapsed disease are eligible, so long as the patient otherwise meets eligibility criteria, i.e., treatment for relapse was completed at least 36 calendar months prior to enrollment and did not include stem cell transplant
Patients with history of hematopoietic stem cell transplant (HSCT) are excluded
Note: Patients with previous chimeric antigen receptor T-cell (CAR T-cell) therapy, and other cellular cancer therapies can participate, as long as all other eligibility criteria are satisfied
Patients with a history of cancers prior to their ALL or AML diagnosis are excluded. Patients that developed a subsequent malignant neoplasm following their ALL or AML diagnosis are also excluded
Note: Prior history of transient abnormal myelopoiesis is allowed, but is not sufficient for eligibility
DS-AL survivors from the Children's Oncology Group (COG) Registry and Epidemiology protocols or locally from participating institutions.
Other
Other
Biospecimen Collection
Procedure/SurgeryPatients undergo saliva/buccal and blood sample collection
Clinical Evaluation
Other interventionUndergo a clinical assessment
Neurocognitive Assessment
Other interventionUndergo neurocognitive assessment
Questionnaire Administration
Other interventionAncillary studies
Survey Administration
Other interventionAncillary studies
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.
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.
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).
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.
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.
Structural birth defects and genetic associations with etiology extending to CHC for Down syndrome acute lymphoblastic leukemia (DS-ALL)
Will determine the association between structural birth defects and the number, organ system category, and severity of CHC in DS-PALS survivors. Will use Cox regression to estimate hazard ratio and 95% CI for number, severity, and type of CHC by number of birth defects. Will explore the role of DS-ALL susceptibility variants identified in our genome-wide assessment on DS-associated CHC in survivors. Will use Cox regression to estimate the association between four DS-ALL susceptibility loci (rs58923657 near IKZF1, rs3731249 in CDKN2A, rs7090445 in ARID5B, and rs3781093 in GATA3) and CHC.
Telomere length (TL) determined by polygenic risk score and telomere flow-fluorescence in situ hybridization (FISH) in association with outcomes from in-person NP assessment for DS-ALL
Will determine genetically-estimated TL. Will use a multivariable Cox proportional hazard model to estimate hazard ratio, 95% CI for the association between each of nine variants and risk for NP deficit =\<1 standard deviation below the mean, and consider the weighted and unweighted risk score from the number of risk alleles present and previously-published beta estimates. For flow-FISH analyses, TL =\< 1st percentile is considered 'very short,' as previously defined. Will determine objective responses for NP deficits =\< 1.5 standard deviation below the mean for an age-normative sample in subjects with TL \> or =\< 1st percentile, adjusted for relevant covariates and treatment factors. Will report 95% CI, p values using a Chi square test (two-tailed p-value of 0.05 statistically significant).
Click on the lead sponsor to view all of their trials.
