TY - JOUR
T1 - Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies
T2 - a prospective pilot study
AU - Williams, Kirsten M.
AU - Holter-Chakrabarty, Jennifer
AU - Lindenberg, Liza
AU - Duong, Quyen
AU - Vesely, Sara K.
AU - Nguyen, Chuong T.
AU - Havlicek, Joseph P.
AU - Kurdziel, Karen
AU - Gea-Banacloche, Juan
AU - Lin, Frank I.
AU - Avila, Daniele N.
AU - Selby, George
AU - Kanakry, Christopher G.
AU - Li, Shibo
AU - Scordino, Teresa
AU - Adler, Stephen
AU - Bollard, Catherine M.
AU - Choyke, Peter
AU - Gress, Ronald E.
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/1
Y1 - 2018/1
N2 - 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 18F-fluorothymidine (18F-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 18F-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. 18F-FLT was not associated with any adverse events or delayed engraftment. 18F-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, 18F-FLT intensity differed significantly between myeloablative infusion before HSCT and subclinical HSC recovery (p=0·00031). 18F-FLT biodistribution over time revealed a previously unknown path of cellular recovery of haemopoiesis in vivo that mirrored fetal ontogeny. Interpretation 18F-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.
AB - 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 18F-fluorothymidine (18F-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 18F-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. 18F-FLT was not associated with any adverse events or delayed engraftment. 18F-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, 18F-FLT intensity differed significantly between myeloablative infusion before HSCT and subclinical HSC recovery (p=0·00031). 18F-FLT biodistribution over time revealed a previously unknown path of cellular recovery of haemopoiesis in vivo that mirrored fetal ontogeny. Interpretation 18F-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.
UR - http://www.scopus.com/inward/record.url?scp=85039049282&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039049282&partnerID=8YFLogxK
U2 - 10.1016/S2352-3026(17)30215-6
DO - 10.1016/S2352-3026(17)30215-6
M3 - Article
C2 - 29248669
AN - SCOPUS:85039049282
SN - 2352-3026
VL - 5
SP - e44-e52
JO - The Lancet Haematology
JF - The Lancet Haematology
IS - 1
ER -