New Test Speeds Time to Determine Success of Bone Marrow Transplants

Scientists have developed a new test that shortens the time it takes to assess the success of bone marrow transplants — to a few days instead of the two to four weeks required when using conventional blood tests.

This is pivotal news for bone marrow transplant recipients, whose risk of developing life-threatening infections increases the longer it takes the new immune cells to multiply and begin to function normally.

The study with these findings, “Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study,” was published in the journal The Lancet Haematology.

For patients with high-risk blood cancers, stem cell transplants might be their only chance for a cure. The approach requires that patients receive a massive chemotherapy dose that kills their hematopoietic stem cells (HSCs) – which give rise to all blood cells – before receiving healthy stem cells from a donor.

While the new stem cells are left to enter the bone marrow and start producing new blood cells, patients are left without an immune system. This leaves them highly vulnerable to potentially fatal infections.

Until now, daily blood tests have been used to assess whether the newly transplanted healthy cells have survived and started to multiply in the bone marrow, a process called engraftment. But it takes two to four weeks, sometimes more, before doctors have an idea about whether the transplant was successful.

The new test allows the engraftment process to be tracked with imaging techniques, including positron emission tomography (PET) and computed tomography (CT) scans, helping doctors assess the success of a transplant early.

This means that unsuccessful stem cell transplants can be detected earlier, in time to allow rapid mobilization of a new transplant, reducing infections and potentially saving lives.

The approach uses a radio-labelled molecule, called 18F-fluorothymidine (18F-FLT), that enters highly proliferating cells, like stem cells, lymphocytes – a type of white blood cell – and cancer cells, and becomes temporarily trapped inside them. This functions as a marker of active cell proliferation.

The study was part of a clinical trial (NCT01338987) that investigated if 18F-FLT could be used to visualize transplanted stem cells safely and efficiently, and to identify successful transplants earlier than current methods.

The study included 23 patients with various forms of high-risk leukemia who received bone marrow transplants from healthy donors after their own HSCs were destroyed.

Imaging was done one day before the transplant and then at five or nine days, 28 days, and one year afterward.

The method was safe and effectively detected evidence of successful transplants after only five days. Interestingly, the location of the new stem cells in the body could be seen by the patients themselves.

“Through the images we took, these patients could see the new cells growing in their bodies,” Kirsten M. Williams, MD, blood and bone marrow transplant specialist at Children’s National Health System, said in a press release. “They loved that.”

The fate of transplanted HSCs after infusion is not known. But the team found that after being infused into a patient’s blood, the stem cells first migrated to the their liver and spleen, then to parts of the spine, the sternum and the arms and legs. By one year, they were concentrated in the bones of the trunk of the body.

This is similar to the way HSCs migrate in the fetus, Williams said.

The technique provides not only an early indication about engraftment status, it also could help avoid painful bone marrow biopsies or help target those biopsies, she said.

“We have shown a novel way to visualize and assess subclinical haemopoietic engraftment with 18F-FLT imaging, suggesting that 18F-FLT could be used as a biomarker of haemopoiesis. 18F-FLT imaging enabled safe, comprehensive, and non-invasive assessment of the entire bone-marrow compartment and showed the pattern of cellular recovery in adults after transplantation,” the investigators concluded.

“18F-FLT imaging seems to be a useful method to assess bone-marrow proliferation in normal and pathological states. 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,” Anthony F. Shields, MD, PhD, of the Karmanos Cancer Institute, at Wayne State University, wrote in an accompanying editorial.