Imaging and Blood Tests for Graft Failure Detection

(REVEAL Trial)

Recruiting at 4 trial locations

Overseen By Jennifer Holter, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Oklahoma

Disqualifiers: Psychiatric disorder, Organ dysfunction, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

56 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find new tests that could help determine if the newly infused bone marrow cells are growing well after bone marrow transplantation or if new bone marrow cells are needed. The Investigator will use FLT imaging, an investigational imaging test, and collect blood samples to investigate whether the cells are growing well.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment FLT imaging, Fluorothymidine imaging, 18F-FLT PET imaging, FLT-PET-MRI imaging, and TK1 blood measurements for detecting graft failure?

The research does not directly address the effectiveness of FLT imaging or related techniques for detecting graft failure, but similar imaging methods like 18F-FDG-PET/CT have shown high sensitivity in detecting infections in vascular grafts, suggesting potential usefulness in assessing graft viability. ^{1 2 3 4 5}

Is FLT imaging and related techniques safe for humans?

The research does not provide specific safety data for FLT imaging or related techniques like 18F-FLT PET imaging and TK1 blood measurements, but it does mention the use of similar imaging methods in clinical settings, suggesting they are generally considered safe for human use. ^{6 7 8 9 10}

How does the treatment for graft failure detection differ from other treatments?

This treatment uses advanced imaging techniques like 18F-fluorodeoxyglucose positron emission tomography (PET) combined with computed tomography (CT) to detect infections in vascular grafts, offering high sensitivity compared to traditional methods. It is unique because it combines imaging with blood tests to improve the accuracy of diagnosing graft infections, which are often difficult to detect with conventional imaging alone. ^{2 3 5 11 12}

Research Team

Kirsten M Williams, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for patients aged 4-70 at high risk of graft failure after bone marrow transplant, such as those with cord blood HSCT or haplo HSCT. Participants must not have had investigational therapies in the last 28 days and should be in remission before HSCT. Pregnant individuals, those with certain allergies, active malignancies outside the hematopoietic system, significant systemic illness, or psychiatric disorders affecting compliance are excluded.

Inclusion Criteria

For Arm A: Absence of donor specific antibodies to cord HLA for cord blood recipients, ≥ 5/10 and < 7/8 allele mismatch donor for haplo-identical recipients, diagnosed with a condition for which myeloablative HSCT is standard of care and HSCT is planned, total bilirubin < 2.5 mg/dL (unless documented Gilbert's syndrome) and transaminases (ALT and AST) < 5 x the upper limit of normal, creatinine clearance or GFR > 60 ml/min/1.73 m2, FEV1 > 80% pre or post-bronchiolator whichever is higher, DLCO Adj > 70%, Sa02 > 94% on room air, ejection fraction > 50%

I am between 4 and 80 years old and at high risk for graft failure after a stem cell transplant.

I can undergo FLT imaging without needing to be put to sleep.

Exclusion Criteria

I cannot or will not use birth control during the study.

I have chosen not to participate in the CIBMTR research study.

Pregnant or lactating females

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Imaging

FLT PET/CT imaging occurs one day prior to hematopoietic stem cell transplantation (HSCT)

1 day

1 visit (in-person)

Post-Transplant Monitoring

FLT imaging and blood biomarker analysis to monitor engraftment on days 9 and 28 after HSCT

28 days

3 visits (in-person)

Nonengraftment Evaluation

For patients not engrafted by day 24, a single FLT PET/CT image is taken within one week to assess graft failure versus delayed engraftment

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• FLT imaging
• TK1 blood measurements

Trial Overview The study is testing FLT imaging and TK1 blood measurements to see if they can help determine how well new bone marrow cells are growing post-transplantation. It's looking for better tests to decide if a patient's newly infused bone marrow cells are engrafting successfully or if another transplant might be needed.

Participant Groups

Group I: Nonengrafted cohort Experimental Treatment 1 Intervention

Pediatric and adult patients who have not engrafted by day 24 after cord or haplo-identical HSCT will undergo a single FLT PET/CT image within one week to determine if this scan can identify graft failure versus delayed engraftment.

Group II: Cord and haplo imaging cohort Experimental Treatment 1 Intervention

For all pediatric and adult patients undergoing cord blood HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 9 and 28 after HSCT. For recipients of haplo-HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 5 and 28 after HSCT.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

University Hospitals Cleveland Medical Center

Collaborator

Trials

348

Recruited

394,000+

University Hospital of Cleveland

Collaborator

Trials

1

Recruited

60+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Findings from Research

In a pilot study involving 7 patients with multiligament reconstructed knees, fluorodeoxyglucose positron emission tomography (PET) combined with CT successfully detected increased metabolic activity in replacement grafts during the first two years post-surgery.

The imaging technique showed significantly higher fluorodeoxyglucose uptake in the operated knees compared to the non-operated side, indicating its potential as an effective method for assessing graft viability and metabolism, although further research with larger groups is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tendon Graft Healing in Multiligament Reconstructed Knee Detected by FDG-PET/CT: A Pilot Study. Itälä, A., Alihanka, S., Kosola, J., et al.[2017]

White blood cell imaging using isotopes like 111In or 99mTc-HMPAO is a sensitive and specific method for detecting vascular graft infections, particularly effective for perioperative or low-grade infections compared to conventional imaging techniques.

The study highlights three case reports where isotopic imaging successfully confirmed the diagnosis of vascular graft infection, underscoring its utility in challenging diagnostic situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How I explore ... value of isotopic techniques in the detection of sepsis in valvular prostheses]. Karsera, D., Belhocine, TZ., Foidart-Willems, J., et al.[2016]

In a study of 152 patients suspected of having vascular graft and endograft infection (VGEI), the use of 18F-fluoro-D-deoxyglucose positron emission tomography with low dose CT ([18F]FDG-PET/LDCT) demonstrated high sensitivity (91%) but lower specificity (72%) for diagnosing VGEI.

Less than half of the [18F]FDG-PET/LDCT reports met all pre-selected reporting criteria, and reports that were incomplete showed significantly lower sensitivity and specificity, highlighting the need for standardized reporting guidelines to improve diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability of [18F]FDG-PET/LDCT reporting in vascular graft and endograft infection. Liesker, DJ., Legtenberg, S., Erba, PA., et al.[2023]

Early graft patency is crucial for reducing complications after coronary artery bypass surgery, with surgical errors contributing to early graft failure, particularly within the first year.

Transit time flowmetry (TTFM) is the most widely used method for intraoperative graft evaluation, yet only about 20% of North American cardiac surgeons utilize it; combining TTFM with high-resolution epicardial ultrasonography enhances diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Techniques for intraoperative graft assessment in coronary artery bypass surgery. Ohmes, LB., Di Franco, A., Di Giammarco, G., et al.[2020]

In a study involving 13 dogs with Dacron aortic grafts, Indium-111-labeled leukocyte imaging demonstrated a sensitivity of 71%, specificity of 100%, and overall accuracy of 85% in detecting early vascular graft infections.

The study found that false-positive results were not an issue in the early postoperative period, suggesting that leukocyte scanning could be a reliable diagnostic tool for identifying graft infections clinically.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of acute synthetic vascular graft infection with 111In-labeled leukocyte scanning: an animal study. Dries, DJ., Alazraki, N., Lawrence, PF., et al.[2016]

Combining advanced imaging techniques like MSCT with PET or scintigraphy enhances the ability to assess blood flow and tissue viability in patients with atherosclerosis, which can improve diagnosis and treatment decisions.

MSCT alone has already significantly transformed cardiology practices by providing accurate and clear imaging for calcium scoring and coronary angiography, making it a valuable tool for screening high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission and computed tomographies in cardiology. Toussaint, JF.[2016]

A study involving 60 kidney transplant patients demonstrated that low-dose three-dimensional MR renography can effectively differentiate between causes of acute graft dysfunction, such as acute rejection and acute tubular necrosis (ATN).

Significant differences in glomerular filtration rate (GFR) and mean transit time (MTT) were observed between patients with normal kidney function and those with acute dysfunction, indicating that this imaging technique provides valuable insights into kidney health post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative evaluation of acute renal transplant dysfunction with low-dose three-dimensional MR renography. Yamamoto, A., Zhang, JL., Rusinek, H., et al.[2021]

The study evaluated the use of rapamycin-treated 18F-FDG-labeled splenocytes for imaging skin allografts in mice, revealing that rapamycin significantly impaired the migration of these cells to the graft site, which could affect imaging efficacy.

In vivo imaging showed that allografts receiving untreated splenocytes (FC cells) had significantly higher radioactivity compared to those receiving rapamycin-treated splenocytes (FR cells), indicating that rapamycin may hinder the effectiveness of this imaging strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti‑migratory effect of rapamycin impairs allograft imaging by 18F‑fluorodeoxyglucose‑labeled splenocytes. Sun, H., Cheng, D., Ma, Y., et al.[2017]

The study evaluated 95 kidney transplant recipients using 18F-FDG PET/CT imaging to assess kidney allograft rejection, demonstrating high repeatability and reproducibility in measuring renal 18F-FDG uptake.

Intra-class correlation coefficients (ICC) showed excellent consistency for intra-observer measurements (0.96) and good inter-observer reproducibility (ranging from 0.83 to 0.87), indicating that this imaging technique can reliably be used in clinical practice to evaluate kidney transplant health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observer variability in the assessment of renal 18F-FDG uptake in kidney transplant recipients. Jadoul, A., Lovinfosse, P., Bouquegneau, A., et al.[2021]

Advancements in imaging technologies, such as cardiovascular magnetic resonance and computed tomography, have significantly improved the ability to monitor heart health and graft function after cardiac transplantation, enhancing patient survival rates.

This review highlights the strengths and weaknesses of various imaging techniques, emphasizing their roles in assessing tissue composition and myocardial metabolism, which are crucial for effective graft surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging imaging techniques after cardiac transplantation. McDiarmid, AK., Plein, S., Ross, HJ.[2018]

In a study of 15 heart transplant patients, 13N-ammonia PET imaging demonstrated excellent correlation with cardiovascular magnetic resonance (CMR) imaging for measuring myocardial strain, indicating its effectiveness in assessing cardiac function post-transplant.

The study found high reproducibility in strain measurements from PET, with intraclass correlation coefficients of 0.89 for circumferential strain and 0.85 for longitudinal strain, suggesting that PET can be a reliable tool for detecting cardiac allograft vasculopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

13N-ammonia positron emission tomography-derived left-ventricular strain in patients after heart transplantation validated using cardiovascular magnetic resonance feature tracking as reference. Kawakubo, M., Nagao, M., Kikuchi, N., et al.[2022]

18F-fluorodeoxyglucose (FDG) PET or PET/CT demonstrated a high sensitivity of 96% for detecting vascular prosthetic graft infections (VPGI) across 10 studies involving 286 patients, indicating it is very effective at identifying these infections.

The specificity was moderate at 74%, suggesting that while the test is good at detecting infections, there may be some false positives, and further large multicenter studies are needed to confirm its clinical usefulness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of 18F-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography for detection of infected prosthetic vascular grafts. Kim, SJ., Lee, SW., Jeong, SY., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Tendon Graft Healing in Multiligament Reconstructed Knee Detected by FDG-PET/CT: A Pilot Study. [2017]

2. Belgium pubmed.ncbi.nlm.nih.gov

[How I explore ... value of isotopic techniques in the detection of sepsis in valvular prostheses]. [2016]

3. Germany pubmed.ncbi.nlm.nih.gov

Variability of [18F]FDG-PET/LDCT reporting in vascular graft and endograft infection. [2023]

4. China pubmed.ncbi.nlm.nih.gov

Techniques for intraoperative graft assessment in coronary artery bypass surgery. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Detection of acute synthetic vascular graft infection with 111In-labeled leukocyte scanning: an animal study. [2016]

6. France pubmed.ncbi.nlm.nih.gov

Positron emission and computed tomographies in cardiology. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Quantitative evaluation of acute renal transplant dysfunction with low-dose three-dimensional MR renography. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

Anti‑migratory effect of rapamycin impairs allograft imaging by 18F‑fluorodeoxyglucose‑labeled splenocytes. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Observer variability in the assessment of renal 18F-FDG uptake in kidney transplant recipients. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Emerging imaging techniques after cardiac transplantation. [2018]

11. Japan pubmed.ncbi.nlm.nih.gov

13N-ammonia positron emission tomography-derived left-ventricular strain in patients after heart transplantation validated using cardiovascular magnetic resonance feature tracking as reference. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of 18F-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography for detection of infected prosthetic vascular grafts. [2020]