Novel imaging offers insights on engraftment process after HSCT

Following a hematopoietic stem cell transplant, a novel imaging test using ¹⁸F-fluorothymidine identified success of engraftments weeks before a traditional blood test, according to study results.

This imaging technique — which can offer patients a less painful option than bone marrow biopsies — also allowed researchers to better understand the process of engraftment following HSCT.

“Although the homing of hemopoietic stem cells to bone marrow has been studied in detail in mice, the pathway to engraftment in human beings is poorly understood,” Kirsten M. Williams, MD, blood and bone marrow transplant specialist at Children’s National Health System, and colleagues wrote. “Various imaging methods can revel cellular events in bone marrow, but available techniques have had poor sensitivity and specificity.”

Williams and colleagues studied the investigational imaging agent ¹⁸F-fluorothymidine (18FLT) following HSCT to understand the pattern of stem cell migration and identify successful engraftment.

18FLT is a thymidine analogue that is radioactive and is present in hemopoietic stem cells, as well as lymphocytes and cancer cells.

The researchers studied 23 patients with high-risk leukemia who underwent myeloablation followed by HSCT. Researchers then scanned patients with the novel 18FLT PET and CT scans at day 5, day 9, day 28 and at 1-year post transplant.

Inclusion criteria included Landsky or Karnofsky score of more than 60%; life expectancy longer than 3 months; organ function sufficient to tolerate myeloablative HSCT; absence of infections, uncontrolled psychiatric disorders or pregnancy; and no previous exposure to 18FLT.

Initial scans identified subclinical bone-marrow recovery within 5 days of infusion for the 21 patients who did not relapse.

Median follow up was 4.3 years. Median time to engraftment was 15 days (range, 13-19) for peripheral blood stem cell grafts and 20 days (range, 17-22) for bone-marrow grafts.

Researchers observed the pattern of activation of bone marrow with initial uptake in the thoracic spine, followed by the axial skeleton and sternum and then the extremities. This pathway is the same as that observed in a fetus when hemopoietic stem cells are formed, according to Williams.

All patients who did not relapse had successful engraftments.

18FLT did not appear associated with adverse events or delayed engraftment.

“Our findings suggest that 18FLT could be useful to assess subclinical engraftment in populations at the highest risk of nonengraftment, including recipients of cord-blood transplants in which cell doses might be inadequate to recover hemopoiesis,” Williams and colleagues wrote.

Limitations of the study included the small population, scans at only one site and the inability to confirm imaging findings through invasive methods due to ethical concerns.

“18FLT imaging seems to be a useful method to assess bone-marrow proliferation in normal and pathological states,” Anthony F. Shields, MD, PhD, professor of medicine and oncology and associate center director for clinical sciences at Karmanos Cancer Institute at Wayne State University, wrote in an accompanying editorial. “This technique will be helpful in elucidating the distribution of activity in bone marrow and in monitoring response to treatment and might prove clinically useful in directing treatment changes.

“A multicenter study is underway in the U.S. to assess the negative predictive value of 18FLT uptake in bone marrow on PET done 10 to 17 days after the start of chemotherapy for clinical complete response,” he added. – by Cassie Homer

Disclosures: The authors and Shields report no relevant financial disclosures.