# Imaging and Blood Biomarkers to Predict Graft Failure after HSCT

> **NIH NIH R01** · EMORY UNIVERSITY · 2023 · $581,140

## Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) has allowed patients to be cured from previously
incurable cancers or hematopoietic diseases by ablating the host immune system and infusing healthy blood
stem cells from a healthy donor. Graft failure, the absence of cellular recovery after HSCT, is a significant
complication of transplant. When graft failure is diagnosed late, as it frequently is, the outcome is devastating.
We have identified novel imaging and blood biomarkers that can detect subclinical engraftment early after
HSCT and could expedite this diagnosis and rescue through re-transplantation. In our published study, the
imaging biomarker, (18)F-fluorothymidine (FLT) PET/CT, detected subclinical engraftment quantitatively in
adults within 5 days of HSCT, illuminating the pathway of subclinical cellular repopulation in bone marrow. All
patients engrafted and there were no toxicities associated with the procedure. Our study also showed that the
serum enzyme, thymidine kinase 1 (TK1), a novel blood biomarker of HSC proliferation, increased co-incident
with cellular recovery. Collectively, these data suggest that FLT imaging and TK1 blood levels may have the
potential to distinguish between subclinical engraftment and graft failure. We now propose to evaluate whether
these biomarkers can identify delayed engraftment or failure in the patients who are at highest risk for this
complication: recipients of cord blood and haplo-identical HSCT. We hypothesize that FLT uptake will identify
subclinical engraftment early after HSCT in alternative donor transplant settings and that FLT and TK1 will
serve as predictive biomarkers of graft failure. We will test these in three specific aims: 1) To determine
whether FLT marrow signal intensity identifies subclinical engraftment and maps distribution of early marrow
settling after cord blood or haplo-identical transplantation, 2) To determine whether FLT marrow signal intensity
distinguishes between engraftment and graft failure in very high-risk alternative donor HSCT recipients, and 3)
To determine whether serum TK1 enzyme levels can distinguish subclinical engraftment from graft failure.
Upon completion of these aims, we expect to show that these blood and imaging biomarkers can predict graft
failure in patients at highest risk for this complication. If confirmed, FLT and TK1 could be used to identify
primary graft failure early after HSCT, permitting expeditious rescue HSCT and significantly improved
outcomes.

## Key facts

- **NIH application ID:** 10672998
- **Project number:** 5R01HL146668-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jennifer Lin Holter Chakrabarty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $581,140
- **Award type:** 5
- **Project period:** 2019-09-25 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10672998

## Citation

> US National Institutes of Health, RePORTER application 10672998, Imaging and Blood Biomarkers to Predict Graft Failure after HSCT (5R01HL146668-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10672998. Licensed CC0.

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