MedicalResearch.com Interview with:
Kirsten Williams, M.D.
Blood and marrow transplant specialist
Children’s National Health System
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study addressed a life-threatening complication of bone marrow transplantation called bone marrow failure. Bone marrow transplantation has provided a cure for patients with aggressive leukemias or acquired or genetic marrow dysfunction. The process of bone marrow transplantation involves giving chemotherapy and/or radiation, which removes the diseased blood cells from the bone marrow. After this, new bone marrow stem cells are infused from a healthy individual. They travel to the bone marrow and start the slow process of remaking the blood system. Because these new cells start from infancy, it takes upwards of four to five weeks for new mature healthy cells to emerge into the blood, where they can be identified. Historically, there has been no timely way to determine if the new cells have successfully repopulated unless they can be seen in the blood compartment. This condition of bone marrow failure is life-threatening, because patients don’t have white blood cells to protect them from infection. Once bone marrow failure is diagnosed, a second new set of stem cells are infused, often after more chemotherapy is given. However, for many individuals this re-transplantation is too late, because severe infections can be fatal while waiting cells to recover.
We were the first group to use a new imaging test to understand how the newly infused bone marrow cells develop inside the patient. We have recently published a way to detect the new bone marrow cell growth as early as five days after the cells are given. We used an investigational nuclear medicine test to reveal this early cell growth, which could be detected weeks before the cells appear in the blood. This radiology test is safe, does not cause any problems and is not invasive. It is called FLT (18F-fluorothymidine) and the contrast is taken up by dividing hematopoietic stem cells. The patients could even see the growth of their new cells inside the bone marrow (which they very much enjoyed while waiting to see recovery of the cells in their blood). We could use the brightness of the image (called SUV) to determine approximately how many weeks remained before the cells were visible in the blood.
Finally, we actually could see where the new cells went after they were infused, tracking their settling in various organs and bones. Through this, we could see that cells did not travel directly to all of the bones right away as was previously thought, but rather first went to the liver and spleen, then to the mid-spine (thorax), then to the remainder of the spine and breastplate, and finally to the arms and legs. This pattern of bone marrow development is seen in healthy developing fetuses. In this case, it occurs in a similar pattern in adults undergoing bone marrow transplant.
MedicalResearch.com: What should readers take away from your report?
Response: There are several important findings from this work.
First, this investigational imaging test (FLT) may be valuable to help us diagnose graft failure earlier and decrease the likelihood of patients succumbing to a severe infection while awaiting cell recovery.
Second, this test may help us to understand how newly infused bone marrow cells develop.
Finally, we now may have the opportunity to see into the bone marrow space to understand what is happening without needing to perform a painful invasive procedure (bone marrow biopsy) or to more directly identify where to biopsy, if necessary.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Now that we have shown that the imaging test is safe and reveals the events inside the bone marrow, we have designed a follow-up study to use the test in patients who are at high risk for bone marrow failure (those who receive mismatched transplants or lower doses of cells from cord blood). We hypothesize the test could successfully identify patients who need an emergent life-saving new transplant of healthy bone marrow. We had previously used the test in patients at low risk for this problem and, thankfully, all of the patients had recovery of cells within the expected timeframe.
We are now analyzing the FLT images to determine whether we can use the test to identify other marrow events, such as the recurrence of leukemia. This would offer additional opportunities to identify relapse of cancer earlier and permit interventions, such as immunotherapy, to try to help cure these patients.
Disclosures: We have submitted a patent application for this work.
Kirsten M Williams, Jennifer Holter-Chakrabarty, Liza Lindenberg, Quyen Duong, Sara K Vesely, Chuong T Nguyen, and others
The Lancet Haematology, Vol. 5, No. 1, e44–e52
Published: December 13, 2017
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