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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e44-e52
JournalThe Lancet Haematology
Volume5
Issue number1
DOIs
StatePublished - Jan 2018

ASJC Scopus subject areas

  • Hematology

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