462 Novel Imaging Analysis of the Marrow Compartment after Myeloablative HSCT Reveals the Kinetics and Degree of Myeloablation and Cell Recovery

Track: Poster Abstracts
Saturday, February 14, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Jennifer Holter Chakrabarty, M.D. , Hematology/Oncology, University of Oklahoma -Peggy and Charles Stephenson Cancer Center, Oklahoma City, OK
Chuong T Nguyen, PhD , * Co-First School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK
Joseph P Havlicek, PhD , School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK
Sara K Vesely, PhD , Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, OK
Liza Lindenberg, MD , Molecular Imaging Branch, NIH, Bethesda, MD
Steve Adler, PhD , Molecular Imaging Branch, NIH, Bethesda, MD
Bazetta AJ Blacklock-Schuver, RN , ETIB/NCI/NIH, Bethesda, MD
Karen Kurdziel, MD , Molecular Imaging Branch, NIH, Bethesda, MD
Frank Lin, PhD , Cancer Imaging Program, National Cancer Institute, NIH, Bethesda, MD
Daniele Avila, CRNP , ETIB/NCI/NIH, Bethesda, MD
George B. Selby, MD , Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Jennifer Mann, NP , ETIB/NCI/NIH, Bethesda, MD
Jennifer Hsu, RN , ETIB/NCI/NIH, Bethesda, MD
Amy Chai, RN , ETIB/NCI/NIH, Bethesda, MD
Robert B. Epstein, MD , Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Ngoc Quyen T Duong, PhD , Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Shibo Li, MD , Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Teresa Kraus, MD , Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Sarah Hopps, PharmD, BSPS, BCOP , University of Oklahoma, Oklahoma City, OK
Tom Pham, MSI , Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Catherine M. Bollard, MD , Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC
Peter Choyke, MD , Molecular Imaging Branch, NIH, Bethesda, MD
Ronald Gress, MD , * Co-Senior Experimental Transplantation and Immunology Branch/NCI/NIH, Bethesda, MD
Kirsten M. Williams, MD , CNMC/National Cancer Institute, NIH, Bethesda, MD
Presentation recording not available for download or distribution as requested by the presenting author.

There are no tests that diagnose graft failure early after hematopoietic stem cell transplantation (HSCT); currently, biopsies of single sites are used, thereby limited by small volume of HSCs. To enhance evaluation of the entire marrow space, we have developed a new methodology using an imaging probe, 3'-deoxy-3 18F-fluorothymidine (18FLT) PET/CT.  Previously, by drawing regions of interest on 18FLT PET-CTs, uptake correlated with rate of engraftment after HSCT. This approach is limited by subjective choice of regions within bones. To enhance objectivity and sensitivity, we developed a computer-based algorithm to isolate the entire medullary space and determine standard uptake value (SUV). This method was applied to images from 17 patients prospectively enrolled on NCT01338987, who underwent myeloablative HSCT for leukemia. Images analyzed included: 1) after ablation (day-1) evaluating for residual hematopoiesis, 2) early engraftment after HSCT (day +5-12), and 3) 28 days after HSCT, full marrow reconstitution. The algorithm sensitively excluded uptake from non-marrow sources by means of a CT mask that identified bone structures and measured the total functional volume within the axial skeleton (Figure 1). Spinal and pelvic medullary volumes from CT mask were median of 586.6 mL (range 400.9- 808.2 mL) and a median of 860.2 mL (range 592.8-1054.1ml) respectively. As expected, CT generated volume correlated significantly with height (cm) in spine (p=.0002, R2=0.62) and pelvis (p=.0125, R2=0.37), and ideal body weight (kg) in spine (p<.0001, R2=0.74) and pelvis (p=.0012, R2=0.54).  SUV ranged from 0.6 to 4; marrow activity was defined > than 1.2, per published literature.   All patients were neutropenic following HSCT, engrafted in the expected time frame, and showed full donor chimerism.  After myeloablation in the 14 non-relapse patients, less than 2% of the axial skeleton demonstrated activity (range <1%-13%).  By day 5-6 after HSCT, this increased 8-fold to 17%(range 1%-28%), and it increased  by 36-fold by day 9-12 to 72%(range 56%-89%).  After 28 days, repopulated marrow showed proliferative activity of 96% (81-99%) (p<0.02 between all 4 time points). In summary, using a semi-automated analysis of 18FLT uptake, we show that hematopoiesis of entire axial skeleton with a single image, which also correlates with height and ideal body weight, suggesting that this is an accurate and sensitive assessment of the medullary space.  Further, we show that imaging may assess the degree of myeloablation after HSCT, and that SUV can describe the degree of marrow engraftment.  Our data show that 18FLT could reveal failure of myeloablation and engraftment failure within 5-6 days of HSCT, which could be used to direct novel therapies and improve outcomes.

Figure 1. FLT image reconstruction axial spine

Figure 2. FLT medullary uptake during myeloablation and marrow repopulation

Disclosures:
Nothing To Disclose
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