18-FLT PET/MR Imaging to Predict Graft Failure and GVHD in Bone Marrow Transplant Patients
| Status: | Recruiting |
|---|---|
| Conditions: | Orthopedic, Hematology |
| Therapuetic Areas: | Hematology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 3/1/2019 |
| Start Date: | January 1, 2017 |
| End Date: | June 2020 |
| Contact: | Kristine Baluyot, BS |
| Email: | kristine_baluyot@med.unc.edu |
| Phone: | 919-843-5420 |
18-FLT PET/MR Imaging to Predict Graft Failure and Graft Versus Host Disease in Bone Marrow Transplant Patients
Allogeneic HSCT is potentially curative for numerous high risk hematologic malignancies and
offers several advantages over traditional chemotherapy. First, higher doses of cytotoxic
chemotherapy and/or irradiation can be given since patients are subsequently rescued from the
severe myelosuppression induced by the pre-transplant conditioning regimen by the infusion of
healthy hematopoietic stem cells.
Second and perhaps more importantly, mature T cells contained in the graft are able to mount
immune responses against residual cancer cells surviving the conditioning regimen due to
major and/or minor MHC disparities between the donor and recipient. Unfortunately, the
allo-immune responses driving the GVL effect are typically not specific for malignant cells.
As a consequence, donor immune cells attack normal host tissues resulting in a process known
as acute graft-versus-host disease (GVHD). Acute GVHD is primarily T cell driven, usually
occurs within the first few months after transplant, and results in skin rash, diarrhea,
cholestatic liver damage, and, on occasion, acute lung injury.
offers several advantages over traditional chemotherapy. First, higher doses of cytotoxic
chemotherapy and/or irradiation can be given since patients are subsequently rescued from the
severe myelosuppression induced by the pre-transplant conditioning regimen by the infusion of
healthy hematopoietic stem cells.
Second and perhaps more importantly, mature T cells contained in the graft are able to mount
immune responses against residual cancer cells surviving the conditioning regimen due to
major and/or minor MHC disparities between the donor and recipient. Unfortunately, the
allo-immune responses driving the GVL effect are typically not specific for malignant cells.
As a consequence, donor immune cells attack normal host tissues resulting in a process known
as acute graft-versus-host disease (GVHD). Acute GVHD is primarily T cell driven, usually
occurs within the first few months after transplant, and results in skin rash, diarrhea,
cholestatic liver damage, and, on occasion, acute lung injury.
The current proposal explores the use of a novel imaging modality, FLT PET/MRI, to correlate
allogeneic transplant outcomes with FLT and MRI findings during early stem cell engraftment
and at a later time point following stable count recovery. Specifically, this study will
determine if the strength of the early FLT signal within the bone marrow correlates with
engraftment success and if isolated areas of cellular proliferation within the marrow at a
later time point might predict for leukemia relapse. In addition, based on the important role
that host lymphoid tissues are known to play in GVHD pathogenesis in mice, this study will
determine if the FLT signal within host SLT after transplant can predict for the development
of GVHD in human BMT patients. Because FLT imaging by itself cannot distinguish between bone
marrow engraftment/proliferation and the allo-immune driven T cell expansion that ultimately
results in GVHD, this study will image autologous transplant patients as a comparator arm.
Autologous HSCT like allogeneic transplantation involves the administration of very high
doses of chemotherapy to high risk cancer patients in order to achieve better tumor kill.
However, in this situation patients are administered their own cryopreserved stem cells to
reconstitute the ablated hematopoietic system. Under those circumstances there is no
allo-immune reactivity to drive T cell activation and expansion after transplant, and as a
result there is no GVHD in the autologous transplant setting. Thus, these patients will help
us to elucidate how much of the FLT signal seen in the allogeneic setting is the result of
allo-immune driven T cell expansion.
allogeneic transplant outcomes with FLT and MRI findings during early stem cell engraftment
and at a later time point following stable count recovery. Specifically, this study will
determine if the strength of the early FLT signal within the bone marrow correlates with
engraftment success and if isolated areas of cellular proliferation within the marrow at a
later time point might predict for leukemia relapse. In addition, based on the important role
that host lymphoid tissues are known to play in GVHD pathogenesis in mice, this study will
determine if the FLT signal within host SLT after transplant can predict for the development
of GVHD in human BMT patients. Because FLT imaging by itself cannot distinguish between bone
marrow engraftment/proliferation and the allo-immune driven T cell expansion that ultimately
results in GVHD, this study will image autologous transplant patients as a comparator arm.
Autologous HSCT like allogeneic transplantation involves the administration of very high
doses of chemotherapy to high risk cancer patients in order to achieve better tumor kill.
However, in this situation patients are administered their own cryopreserved stem cells to
reconstitute the ablated hematopoietic system. Under those circumstances there is no
allo-immune reactivity to drive T cell activation and expansion after transplant, and as a
result there is no GVHD in the autologous transplant setting. Thus, these patients will help
us to elucidate how much of the FLT signal seen in the allogeneic setting is the result of
allo-immune driven T cell expansion.
Inclusion Criteria:
- Patients undergoing allogeneic bone marrow transplant for acute myeloid leukemia
(AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome
- Allogeneic transplant patients receiving either a fully myeloablative or reduced
intensity chemotherapy +/- total body irradiation (TBI) conditioning regimen are
eligible.
- Allogeneic transplant patients receiving stem cells from a matched related, matched
unrelated, mismatched unrelated, mismatched related (including haplotype matched)
donors are eligible
- Allogeneic transplant patients must be in a complete morphologic remission prior to
transplant
- Patients undergoing autologous bone marrow transplant for multiple myeloma
- Myeloma patients must have achieved at least a very good partial remission prior to
transplant and exhibit fewer than 10% plasma cells in their pre-transplant marrow
biopsy
- At least 18 years of age
- Negative urine pregnancy test in women of child-bearing potential
Exclusion Criteria:
- Any woman who is pregnant or has reason to believe she is pregnant or any woman who is
lactating.
- Condition that makes MRI unsafe (e.g., cardiac pacemaker, epicardial pacemaker leads,
cochlear implants, metal aneurysm clip, metal halo devices)
- Inability to tolerate MRI (e.g., unable to lie flat for > 1 hour, severe
claustrophobia)
- Known allergy to fluorothymidine
- Creatinine clearance < 40 ml/min, as estimated by the Cockcroft-Gault formula
- Body Mass Index (BMI) > 35
- Poorly controlled diabetes mellitus (fasting blood glucose > 500 mg/dl)
- Institutionalized subject (prisoner or nursing home patient)
- Critically ill or medically unstable
- Currently hospitalized (All FLT PET/MR scans will be obtained in the outpatient
setting)
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