Cardiovascular Reserve Evaluation in Survivors of Transplant, CREST Study

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.

• Bioelectric Impedance Analysis (Procedure), also known as BIA, Bioelectric Impedance, Bioelectric Impedance Test, Bioelectrical Impedance Analysis, Bioimpedance Analysis: Undergo bioelectric impedance analysis
• Biospecimen Collection (Procedure): Undergo collection of blood samples
• Cardiopulmonary Exercise Testing (Procedure), also known as CPET, CPX: Undergo cardiopulmonary exercise test
• Echocardiography (Procedure): Undergo echocardiogram
• Physical Performance Testing (Procedure), also known as Physical Fitness Testing, Physical Function Testing: Undergo physical function tests
• Pulmonary Function Test (Procedure), also known as lung function test, PFT, Pulmonary Function Testing, Pulmonary Function Tests: Undergo pulmonary function test
• Questionnaire Administration (Other): Ancillary studies
• Ultrasound (Procedure): Undergo musculoskeletal ultrasound

Primary outcomes

• Cardiovascular reserve capacity, as measured by VO2peak, in HCT survivors [Up to 24 months post-hematopoietic cell transplantation (HCT)]: 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.
• Determinants of VO2peak impairment in HCT survivors [Up to 24 months post-hematopoietic cell transplantation (HCT)]: We will use Generalized Estimating Equation(GEE) and generalized linear models to examine the correlation between VO2peak and measures of: 1. cardiac (left ventricular function/ contractility \[systolic, diastolic, cardiac output, strain\], ventricular-arterial (VA) coupling, arterial elastance); 2. pulmonary (obstructive, restrictive lung disease, diffusion capacity); 3. 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 4. hematologic function, adjusting for potential confounding variables (e.g. age, sex) and time since HCT.

Sex: All, ages: 18 Years to any

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)

• Study Protocol and Statistical Analysis Plan (PDF, 2024-12-11)
• Informed Consent Form (PDF, 2023-08-08)

• Saro H Armenian, Principal investigator, City of Hope Medical Center

NIH grants: P30CA033572, R01HL150069