Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study.
Kirsten M Williams, Jennifer Holter-Chakrabarty, Liza Lindenberg, Quyen Duong, Sara K Vesely, Chuong T Nguyen, Joseph P Havlicek, Karen Kurdziel, Juan Gea-Banacloche, Frank I Lin, Daniele N Avila, George Selby, Christopher G Kanakry, Shibo Li, Teresa Scordino, Stephen Adler, Catherine M Bollard, Peter Choyke, Ronald E Gress
Author Information
Kirsten M Williams: Children's Research Institute, Children's National Health System, Washington, DC, USA. Electronic address: kmwillia@cnmc.org.
Jennifer Holter-Chakrabarty: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Liza Lindenberg: Molecular Imaging Branch, National Cancer Institute, and National Institutes of Health, Bethesda, MD, USA.
Quyen Duong: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Sara K Vesely: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Chuong T Nguyen: School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK, USA.
Joseph P Havlicek: School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK, USA.
Karen Kurdziel: Molecular Imaging Branch, National Cancer Institute, and National Institutes of Health, Bethesda, MD, USA.
Juan Gea-Banacloche: Division of Infectious Diseases, Mayo Clinic Arizona, AZ, USA.
Frank I Lin: Cancer Imaging Program, National Cancer Institute, and National Institutes of Health, Bethesda, MD, USA.
Daniele N Avila: Experimental Transplantation and Immunology Branch, National Cancer Institute, and National Institutes of Health, Bethesda, MD, USA.
George Selby: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Christopher G Kanakry: Experimental Transplantation and Immunology Branch, National Cancer Institute, and National Institutes of Health, Bethesda, MD, USA.
Shibo Li: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Teresa Scordino: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Stephen Adler: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, National Cancer Institute Campus at Frederick, Frederick, MD, USA.
Catherine M Bollard: Children's Research Institute, Children's National Health System, Washington, DC, USA.
Peter Choyke: Molecular Imaging Branch, National Cancer Institute, and National Institutes of Health, Bethesda, MD, USA.
Ronald E Gress: Experimental Transplantation and Immunology Branch, National Cancer Institute, and National Institutes of Health, Bethesda, MD, USA.
BACKGROUND: Haemopoietic stem-cell transplantation (HSCT) eradicates host haemopoiesis before venous infusion of haemopoietic stem cells (HSCs). The pathway to cellular recovery has been difficult to study in human beings because of risks associated with interventions during aplasia. We investigated whether F-fluorothymidine (F-FLT) imaging was safe during allogenic HSCT and allowed visualisation of early cellular proliferation and detection of patterns of cellular engraftment after HSCT. METHODS: Eligible patients were aged 18-55 years, had high-risk haematological malignancies. All patients underwent myeloablation followed by HSCT. The imaging primary endpoint was detection of early subclinical engraftment after HSCT with F-FLT PET or CT. Imaging was done 1 day before and 5 or 9, and 28 days, and 1 year after HSCT. This study is registered with ClinicalTrials.gov, number NCT01338987. FINDINGS: Between April 1, 2014, and Dec 31, 2015, 23 patients were enrolled and assessable for toxic effects after completing accrual. F-FLT was not associated with any adverse events or delayed engraftment. F-FLT imaging objectively identified subclinical bone-marrow recovery within 5 days of HSC infusion, which was up to 20 days before engraftment became clinically evident. Quantitatively, F-FLT intensity differed significantly between myeloablative infusion before HSCT and subclinical HSC recovery (p=0·00031). F-FLT biodistribution over time revealed a previously unknown path of cellular recovery of haemopoiesis in vivo that mirrored fetal ontogeny. INTERPRETATION: F-FLT allowed quantification and tracking of subclinical bone-marrow repopulation in human beings and revealed new insights into the biology of HSC recovery after HSCT. FUNDING: National Institutes of Health, Ben's Run/Ben's Gift, Albert and Elizabeth Tucker Foundation, Mex Frates Leukemia Fund, Jones Family fund, and Oklahoma Center for Adult Stem Cell Research.
