ALTE22C1: Chronic Health Conditions in Down Syndrome-Associated Acute Leukemia: The Down Syndrome Phenotyping Acute Leukemia Study in Survivors (DS-PALS Survivors)
ALTE22C1: DS-PALS Survivors
What is the goal of the study?
Down syndrome (DS) is a genetic disorder characterized by a constitutional trisomy of chromosome 21, neurocognitive delay, phenotypic features, co-occurring structural birth defects, and an increased risk for chronic health conditions (CHC) such as thyroid disease, osteopenia, seizure disorder, and visual/hearing problems. Children with DS have a 10-20 fold excess risk for acute leukemia (AL) compared with the general population, and are also at significantly greater risk for acute therapy-related toxicities. However, few studies have reported late effects of cancer therapy in survivors of DS-AL, and none have investigated whether these CHC differ from those experienced by children with DS and no history of cancer. Therefore, although a higher than expected incidence of late effects is reported in DS-AL survivors, the prevalence and severity of these CHC relative to the CHC associated with DS and no history of cancer is unknown. Further, AL treatment confers well-described risks for deficits in attention, processing speed, and executive function, but only one small case series to date has investigated neuro-psychological (NP) outcomes in DSAL survivors. Due to a systematic exclusion from research based on their differing baseline health status, DS-AL survivors are an at-risk population that is largely unstudied. To address this critical knowledge gap, results from this study will be utilized to characterize late effects experienced by DS-AL childhood cancer survivors, by determining the prevalence and severity of CHC and clinical and NP outcomes in DS-AL survivors. Our primary objective is to compare the prevalence, severity, and timing of CHC in a cohort of DS-AL with age-comparable DS individuals that have no cancer history. Our secondary objectives will compare NP and health-related quality of life outcomes in survivors of DS-AL compared with age-comparable DS individuals with no cancer history, and will identify risk determinants of CHC and NP late effects among survivors of DS-AL. We hypothesize that the prevalence and severity of specific CHC and adverse clinical and NP outcomes will exceed those observed in non-DS patients with AL and in matched DS controls without cancer history. Further, we hypothesize that DS-ALL susceptibility loci will also demonstrate associations with risk for specific CHC, as well as with the incidence of some co-occurring birth defects, in survivors of DS-ALL, specifically. Last, we anticipate that shorter leukocyte telomere length will be associated with adverse NP outcomes in survivors of DS-AL. This multi-site study will characterize cancer treatment outcomes in survivors of DS-AL, establishing an annotated and comprehensively-characterized contemporary survivor cohort and biospecimen bank. We anticipate results of this work to inform clinical practice guidelines for DS-AL survivors, mitigating risk for outcome disparities in this vulnerable population.
Who can participate in the study?
Please contact the study team listed below to learn more.