Cardiovascular Reserve Evaluation in Survivors of Transplant, CREST Study

Study Overview
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Brief Summary
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This study evaluates how well the heart, lungs, and muscles are working individually, and how these systems are working together in transplant survivors. Information collected in this study may help doctors to understand why hematopoietic stem cell transplant survivors are at higher risk for developing cardiovascular disease.

Detailed Description
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PRIMARY OBJECTIVES: I. Evaluate cardiovascular reserve capacity, as measured by peak oxygen consumption (VO2peak), in hematopoietic cell transplantation (HCT) survivors. II. Define the determinants of VO2peak impairment in HCT survivors. OUTLINE: Patients undergo echocardiogram to assess cardiac function and mechanics, cardiopulmonary exercise test, pulmonary function test, musculoskeletal ultrasound, bioelectrical impedance analysis to measure total lean body mass and percent body fat), physical function tests, and collection of blood samples within 45 days from the start of conditioning therapy, and at 6 months, 1 year, and 2 years post-transplant.

Official Title
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Cardiovascular Reserve Evaluation in Survivors of Transplantation (CREST)

Conditions
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Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Hematopoietic and Lymphoid Cell Neoplasm, Hodgkin Lymphoma, Myelodysplastic Syndrome, Non-Hodgkin Lymphoma, Plasma Cell Myeloma

Intervention / Treatment
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* Procedure: Bioelectric Impedance Analysis
* Procedure: Biospecimen Collection
* Procedure: Cardiopulmonary Exercise Testing
* Procedure: Echocardiography
* Procedure: Physical Performance Testing
* Procedure: Pulmonary Function Test
* Other: Questionnaire Administration
* Procedure: Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at HCT >= 18 years Diagnosis of acute leukemia (myeloid, lymphoid), lymphoma (non-Hodgkin, Hodgkin), multiple myeloma or myelodysplastic syndromes Planning to undergo first autologous or allogeneic transplant Able to fluently read and write in English Able to understand and sign the study specific informed consent form (ICF) Physically able and willing to complete all study procedures Exclusion Criteria: Unstable bone lesions per electronic medical record review and/or notification from patient's primary physician Unstable angina or history of acute myocardial Infarction (< 5 days of any planned study procedures) Recurrent syncope Acute myocarditis or pericarditis Symptomatic severe aortic stenosis Uncontrolled arrhythmia causing symptoms Pulmonary embolus < 3 month of study procedures Thrombosis of lower extremities Moderate or severe persistent asthma (National Asthma Education & Prevention) Room air desaturation at rest =< 85% Non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e. infection, renal failure, thyrotoxicosis) Anemia (hemoglobin [Hgb] < 8 g/dL)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (physical assessment)<br>Patients undergo echocardiogram to assess cardiac function and mechanics, cardiopulmonary exercise test, pulmonary function test, musculoskeletal ultrasound, bioelectrical impedance analysis to measure total lean body mass and percent body fat), physical function tests, and collection of blood samples within 45 days from the start of conditioning therapy, and at 6 months, 1 year, and 2 years post-transplant. | Procedure: Bioelectric Impedance Analysis<br>* Undergo bioelectric impedance analysis<br>* Other names: Bioimpedance Analysis;Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>Procedure: Cardiopulmonary Exercise Testing<br>* Undergo cardiopulmonary exercise test<br>* Other names: CPX;Procedure: Echocardiography<br>* Undergo echocardiogram<br>Procedure: Physical Performance Testing<br>* Undergo physical function tests<br>* Other names: Physical Function Testing;Procedure: Pulmonary Function Test<br>* Undergo pulmonary function test<br>* Other names: Pulmonary Function Tests;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Ultrasound<br>* Undergo musculoskeletal ultrasound<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular reserve capacity, as measured by VO2peak, in HCT survivors | We will measure initial VO2peak in patients prior to HCT and its post-HCT trajectory over time; compare VO2peak in HCT survivors at baseline (pre-HCT), 6m, 1Y, and 2Y post-HCT to established age- and sex-normative data; and define the association between VO2peak and self-reported health-related quality of life (HRQOL) at baseline/over time. | Up to 24 months post-hematopoietic cell transplantation (HCT) | 
| Determinants of VO2peak impairment in HCT survivors | We will use Generalized Estimating Equation(GEE) and generalized linear models to examine the correlation between VO2peak and measures of: cardiac (left ventricular function/ contractility [systolic, diastolic, cardiac output, strain], ventricular-arterial (VA) coupling, arterial elastance); pulmonary (obstructive, restrictive lung disease, diffusion capacity); musculoskeletal (body composition [% lean muscle mass], muscle quality, two minute step in place test, 30 second sit to stand test, timed up and go); and hematologic function, adjusting for potential confounding variables (e.g. age, sex) and time since HCT. | Up to 24 months post-hematopoietic cell transplantation (HCT) |