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Trajectories of Neurotoxicity Among Patients with Adolescent and Young Adult Hodgkin Lymphoma

Award Number: R37CA316700
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Trajectories of Neurotoxicity Among Patients with Adolescent and Young Adult Hodgkin Lymphoma - PROJECT SUMMARY Emerging self-report data suggests that up to 40% of adolescents and young adults (AYAs) with cancer experience long-term neurotoxic effects of therapy such as cancer-related cognitive impairment (CRCI) and neuropathy, despite never receiving therapy known to target the central nervous system. While great attention has been paid to these neurotoxicities in younger children and older adults with cancer, they remain severely understudied among AYAs due to unrecognized risk. Hodgkin lymphoma (HL) represents the ideal model to study trajectories of neurotoxic effects of non-CNS directed therapy among AYAs. It is the most common hematologic malignancy among AYAs, has excellent survival (>90%), and is treated with an intensive regimen, but without CNS directed therapy. We have previously demonstrated that long-term adult survivors of pediatric Hodgkin lymphoma who were assessed 20 years post-therapy experience significant neurocognitive impairment and neuropathy that is associated with lower educational attainment, under employment, and decreased quality of life. Further, we have demonstrated that CRCI and neuropathy (both peripheral and autonomic) are comorbid in long-term adult survivors of pediatric cancer and that neuropathy predicts clinically meaningful neurocognitive decline. Lastly, we have demonstrated that long-term survivors of pediatric HL experience chronic inflammation (e.g. increased IL-6, CRP) and oxidative stress (e.g. GpX, and OxLDL) which is associated with neurocognitive impairment indicating that multiple pathways may contribute to neurotoxicities. However, comprehensive data on CRCI and neuropathy during therapy is unavailable and it remains unclear if they begin prior to therapy, develop during treatment, or emerge late, if they are comorbid, and what the underlying shared mechanisms may be. Therefore, we proposed the first nationwide longitudinal study of neurotoxicities among newly diagnosed AYAs with Hodgkin lymphoma. We aim to characterize cognitive function and neuropathy from pre to post treatment and 1 year later in 314 HL and 314 age- sex-matched community controls. We also aim to understand how these two problems may be comorbid or predict one another as well as examine their impact on schooling, employment, and quality of life. Finally, we aim to employ novel machine learning methods to identify profiles of markers of inflammation, oxidative stress, and neuronal damage that predict neurotoxicity. This proposal will generate novel data to inform screening guidelines for neurotoxicity during and after therapy for AYA Hodgkin lymphoma as well as the design of targeted intervention studies. Data is urgently needed to characterize the trajectories of neurocognitive impairment and neuropathy during treatment to determine if these are late-onset consequences of therapy or emerge during therapy and persist over time. Without this understanding, CRCI may continue to be an unrecognized consequence of HL therapy and we will miss an opportunity to develop targeted interventions to simultaneously ameliorate two AYA described high-priority problems impacting their ability to transition to survivorship and achieve their education, vocational, and social goals.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $814,967 )
2026	2026	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Cancer Treatment Research	000	1	7/29/2026	NEW	$814,967
														Subtotal = $814,967

Grand Total All Awards = $814,967

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Trajectories of Neurotoxicity Among Patients with Adolescent and Young Adult Hodgkin Lymphoma

Award Number: R37CA316700

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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