Cancer and treatment-related cognitive changes, such as thinking or remembering, hinder resumption of normal routine and roles and worsen quality of life. Older adults undergoing hematopoietic cell transplantation (HCT) are at high-risk for cognitive impairment. Age is a risk factor for Alzheimer's Dementia (AD) and the hematological malignancies leading to HCT. There are shared mechanisms and interactions between AD and cancer-related cognitive decline (CRCD). Physical activity improves cognitive function in older adults and survivors of other cancers. This study hypothesizes that increasing physical activity can also improve cognitive function in this vulnerable population.

The study has two goals. The first is to adapt and test an evidence-based physical activity intervention, The Community Health Activities Model Program for Seniors II (CHAMPS II), in the HCT setting for adults 55 years and older. This will be done using semi-structured interview of up to 10 patients who have experienced the HCT process within the last 3 to 6 months with HCT care-team partners.

The second goal will explore the prevalence and impact of AD-neuropathology and inflammation on cancer-related cognitive decline (CRCD) in older adults undergoing HCT.

Hematologic malignancies are diseases that primarily affect older adults, with a median age at diagnosis of 65 years. Hematopoietic cell transplantation (HCT) is a potentially curative and life-prolonging treatment for patients with hematologic malignancies. Cancer and treatment-related cognitive changes cause distress, hinder resumption of normal routine and roles, and worsen quality of life. HCT differs from the delivery of chemotherapy in other cancer settings due to the intensity of chemotherapy and severity of toxicity. Older adults undergoing HCT are at high risk for cognitive decline and pervasive cognitive deficits. Interventions to improve cognitive outcomes are needed. The prevalence and risk of cognitive decline post-HCT are greater for older adults because of a greater number of existing health conditions (i.e., vascular disease) and impaired physical and psychologic function pre-HCT that can be exacerbated by treatment and the overall HCT experience.

Exercise training improves cancer-related health outcomes, including cardiorespiratory fitness, inflammation, cancer related fatigue, depressive symptoms, and sleep disturbance. There is consistent evidence showing that physical activity improves cognitive function in older adults and survivors of other cancers. Improvement in cardiorespiratory fitness, brain structure, and inflammation underlie the mechanisms of the cognitive benefits of physical activity. While untested in older adults undergoing HCT, the investigator hypothesizes that increasing physical activity can also improve cognitive function in this vulnerable population.

Physical activity improves the cognitive domains most affected by cancer treatment, namely executive function and working memory. Cognitive function is an important outcome to older adults and has not been a focus of physical activity interventions in the HCT population. In addition, older adults are underrepresented in previous physical activity interventions in the HCT population.

Investigators will adapt CHAMPS II, an evidence-based physical activity intervention, to the HCT setting for older adults to improve cognitive function. This is an individually tailored program that provides information, skills, training, and problem-solving support to older adults. The program provides a foundation for application by including an instructor manual and directions for implementation. CHAMPS-II has been adapted and implemented in diverse communities using existing resources and improving contextual factors to increase physical activity for sedentary older adults.

Adaptation of evidence-based interventions, such as CHAMPS-II, can result in an attenuation of effects if the core components are not maintained. However, adaptations can be made to fit the needs and priorities of the service setting, target audience, mode of delivery, and cultural context without compromising CHAMPS-II effectiveness. Through a research-practice partnership approach, investigators will help adapt the program while maintaining the core components of CHAMPS-II, develop new program materials, provide training, monitor implementation, and conduct program evaluation. The overarching goal is to enable HCT team members to implement CHAMPS-II and leverage existing organizational resources to enhance feasibility and sustainability.

The research plan proposes a hybrid effectiveness-implementation design, which is a design that spans the effectiveness and implementation research to accelerate the translation of physical activity interventions into practice for older adults with cancer. This novel trial design will allow testing of the program within a randomized clinical trial methodology while observing and gathering information on implementation. The effectiveness study condition offers an ideal opportunity to examine implementation issues and plan for implementation strategies for a future study that examines both effectiveness and implementation strategies. The study will use the RE-AIM (Reach, Effectiveness - Adoption, Implementation, and Maintenance) framework for planning and formative and process evaluation of the intervention. Formative and process evaluation provides information needed to evaluate an intervention's potential for translation into clinical practice.

Investigators aim to understand the prevalence and impact of AD-neuropathology and inflammation on cognitive function and structural brain changes in older adults undergoing HCT. Quantifiable AD-related neuropathology can accumulate silently for decades with no clinical symptoms. Some will have no AD pathology, some will have "silent" AD pathology, and some will have clinically relevant levels of AD pathology. Brain volumes is also a measure of cognitive reserve with many factors that could impact brain volumes including aging, AD, other degenerative diseases, untreated obstructive sleep apnea (OSA), chronic stress, and ethyl alcohol or ethanol abuse (ETOH). Some patients with low brain volumes may have negative AD biomarkers. However, brain volumes may be a good predictor of CRCD. Investigators expect to gain an understanding of the prevalence of between-subject variability in the quantity of AD neuropathology and differences in brain volume. The results of this research will lay the groundwork for future funding opportunities to elucidate the bidirectional mechanisms, prevention and treatment of AD and CRCD in this population.

Arm 1:

Inclusion Criteria for Participants:

• age 60 years and older
• have a diagnosis of hematological malignancy
• have received autologous or allogeneic HCT within the prior 3-6 months
• able to speak and read English
• have provided written informed consent

Exclusion Criteria for Participants:

• there are no exclusion criteria

Inclusion Criteria for Participants' Care-Partner:

• age 19 years and older
• able to speak and read English

Exclusion Criteria for Participants' Care-Partner:

• there are no exclusion criteria

Inclusion Criteria for Transplant Team Member:

• age 19 years and older
• able to speak and read English

Exclusion Criteria for Transplant Team Member:

• there are no exclusion criteria

Arms 2 and 3:

Inclusion Criteria for Participants:

• age 55 years and older
• have a diagnosis of hematological malignancy
• planned to receive an autologous or allogeneic HCT
• able to walk 4 meters as part of the Short Physical Performance Battery (with or without assistance)
• (In Arm 3 only): willingness to be randomized to either initiate the physical activity intervention pre-HCT or following Day 180 post-HCT, and to follow the protocol for the group to which they have been assigned
• able to speak and read English
• have provided written informed consent

Exclusion Criteria for Participants:

• development of chest pain, severe shortness of breath, or occurrence of other safety concerns during the physical performance measures (i.e. Short Physical Performance Battery)
• is not cleared to participate in exercise by a physician

Individuals with the following current conditions/diagnoses documented in medical history will be required to provide clearance for exercise from their cardiologist:

• Myocardial infarctions in the past 3 months
• Resting or unstable angina
• Uncontrolled and/or serious arrhythmias
• 3rd degree heart block
• Acute congestive heart failure or ejection fraction <30%
• Clinically significant aortic stenosis

Individuals with the following conditions/diagnoses will be required to provide clearance for exercise from their surgeon:

• Hip fracture, hip or knee replacement, or spinal surgery in the past 3 months

  • other medical, psychiatric, or behavioral factors that in the judgement of the principal investigator may interfere with study participation or the ability to follow either the intervention or the active control condition
  • (In Arm 3 for those who agree to the voluntary measures of blood, saliva and MRI, there are additional exclusions to avoid conditions that may confound study outcomes):

• history of residual brain abnormalities from prior severe traumatic brain injury (e.g. encephalomalacia) or other significant abnormalities documented on a recent brain MRI (e.g. brain cancer, large vessel strokes, residual subdural hematoma)

• history of major stroke with obvious residual deficits

• history of relapsing and remitting Multiple Sclerosis

• active moderate to severe psychiatric symptoms due to primary psychiatric disorder

Inclusion Criteria for Participants' Care-Partner:

• age 19 years and older
• able to speak and read English
• able to walk 4 meters as part of the Short Physical Performance Battery (with or without assistance)
• have no medical contraindications for participating in light to moderate-intensity physical activity per PI review of medical history as reported on the care-partner medical history form

Exclusion Criteria for Participants' Care-Partner:

• development of chest pain, severe shortness of breath, or occurrence of other safety concerns during the physical performance measures (i.e. Short Physical Performance Battery)
• is not cleared to participate in exercise by a physician

Individuals with the following current conditions/diagnoses documented in medical history will be required to provide clearance for exercise from their cardiologist:

• Myocardial infarctions in the past 3 months
• Resting or unstable angina
• Uncontrolled and/or serious arrhythmias
• 3rd degree heart block
• Acute congestive heart failure or ejection fraction <30%
• Clinically significant aortic stenosis

Individuals with the following conditions/diagnoses will be required to provide clearance for exercise from their surgeon:

o Hip fracture, hip or knee replacement, or spinal surgery in the past 3 months

• other medical, psychiatric, or behavioral factors that in the judgement of the principal investigator may interfere with study participation or the ability to follow either the intervention or the active control condition

Inclusion Criteria for Transplant Team Member:

• age 19 years and older
• able to speak and read English

Exclusion Criteria for Transplant Team Member:

• there are no exclusion criteria

The outcomes assessor completing primary outcome testing during the RCT in Aim 3 will be blinded.