Chronic health conditions in survivors of down syndrome-associated leukemia

Active Project Grant Awarded Last action

Award ID
R01CA263000
Recipient
Awarding agency
Obligated
$5,297,026

Award facts

Assistance listing
93.393 Cancer Cause and Prevention Research
Completion date 73% complete
Originally
Place of performance
Houston, TX 77030, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
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 is unknown. Further, AL treatment confers well-described risks for deficits in attention, processing speed, and executive function, but only one small case series has investigated neuro-psychological (NP) outcomes in DS-AL 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, we will 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. Recruiting from DS participants in children's oncology group studies and registries, our methods include both medical record data abstraction and prospective in-person and survey-based assessments. Aim 1 will establish an annotated and comprehensively-characterized, contemporary cohort of DS-AL survivors. Aim 2 will leverage access to a well-established cohort of DS persons without cancer history to compare CHC and NP outcomes with those observed in DS-AL survivors. Aim 3 will identify clinical, genetic, and biological risk determinants of late effects in DS-AL survivors. Based on our strong preliminary data, we hypothesize that the prevalence and severity of specific CHC and adverse clinical and NP outcomes will exceed those observed in non-DS AL and in matched DS controls without cancer history. Further, we expect that DS all susceptibility loci will extend to association with risk for CHC, and correspond with incidence of CO-occurring birth defects. Last, we anticipate that shorter telomere length is associated with adverse NP outcomes. Our multi-disciplinary team has a strong history of collaboration and expertise in leukemia and cancer survivorship (gramatges), DS- AL (rabin), epidemiology of cancer and birth defects (lupo), DS-associated CHC (rosser), NP outcomes in DS survivors (jacola), and CHC in survivors of childhood cancer (chow). With the support of the children's oncology group, this multi-site, national study will characterize cancer treatment outcomes in DS-AL survivors. We anticipate our results will improve survivorship care by informing clinical practice guidelines for DS-AL survivors, mitigating outcome disparities in this vulnerable population.

Transactions

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Subawards

Subrecipient Amount Awarded
Cog Research Foundation, LLC Agreement: $132,250 Sites will be provided with $1,000 per case enrolled in ALTE22C1. These funds will be disbursed by COG Research Foundation to… $132,250
Emory University Agreement: $46,767 Dr. Lupo is a Professor of Pediatrics in the Division of Hematology/Oncology at Emory University. He is also Co-Director of the Research… $46,767
Emory University Agreement: $106,304 Amd 1: $118,780.95 Amd 2: $-43,550.95 Amd 3: $103,767 (P700000795) Amd 4: $11,260 (P700000795) Amd 5: $112,203 Dr. Rosser will lead a team… $408,764
ST Jude Children's Research Hospital Inc. Agreement: $144,863 Amd 1: $120,581 Amd 2: $-7,420 Amd 3: $126,916 (P700000794) Amd 4: -$10,672.60 (P700000794) Amd 5: $133,004 Dr. Jacola will lead a team that… $507,271
The Regents Of The University Of California. San Francisco Agreement: $46,901 This proposal seeks to perform comprehensive phenotyping of Down syndrome acute leukemia childhood cancer survivors and prospectively conduct… $46,901
Public Health Institute Agreement: $78,375 Amend 1: $78,375 Amend 2: $104,500 Study activities will be centralized as much as possible to offset the burden on participating COG… $261,250

Quick answers

Who received award R01CA263000?

R01CA263000 was awarded to Baylor College Of Medicine by National Cancer Institute (National Institutes of Health) on June 20, 2022.

How much is award R01CA263000 worth?

$5,297,026 has been obligated on R01CA263000.

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