A study published in the journal Blood, (Journal of the American Society of Hematology) shows that administration of special chemical called “granulocyte colony-stimulating factor (G-CSF)”, which mobilizes bone marrow stem cells and releases them from the bone marrow into the blood, is unlikely to put healthy stem cell donors at risk for later development of cancer-causing chromosomal abnormalities. The chromosome abnormalities in question involve loss or gains of chromosomes that have been linked to blood-based disorders such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
When given to stem cell donors, G-CSF moves the donor’s stem cells from the bone marrow into the blood stream. This process is called “mobilization.” Once in the blood, physicians and scientists can collect large doses of stem cells from the peripheral blood safely and without invasive surgery (this process is called “apheresis”). Apheresis avoids bone marrow harvests in the operating room, which can be painful, stressful, and require some recovery time. Research has shown that the large doses of mobilized stem cells, called peripheral blood stem cells or PBSCs, can repopulate the bone marrow and create new blood cells faster than stem cells collected directly from the bone marrow. Furthermore, several long-term follow-up studies have demonstrated that healthy donors are not at an increased risk of developing leukemia or other cancers following PBSC donation.
Betsy Hirsch, first author of the study and Associate Professor in the Department of Laboratory Medicine and Pathology at the University of Minnesota Medical School said: “In recent years, PBSCs have become the dominant source of stem cells for stem cell transplants and the number of transplants performed with PBSCs that have been mobilized with G-CSF has substantially increased. However, the potential for the therapy to cause DNA damage, mutations, or cancer had been suggested in a smaller and less comprehensive prior study, raising a serious concern within the transplant community and making a definitive study very important. Our study aimed at investigating potential effects of G-CSF on chromosomes in healthy donors,”
A research team from the University of Minnesota Medical School conducted a study to determine if G-CSF therapy is indeed a potential cause of chromosome loss or gain in stem cell donors. They asked if there was any risk with short-term, low-dose usage of G-CSF on healthy PBSC donors. Their study evaluated blood samples taken from 22 PBSC donors who had received G-CSF and 22 controls patients who had no history of cancer or prior exposure to G-CSF therapy over a 12 month period.
By using a technique called fluorescence in situ hybridization or FISH, the researchers evaluated the white blood cells of the study subjects for abnormal number of chromosomes. FISH is a sensitive laboratory technique that can detect specific targeted regions of DNA in an individual’s cells to identify chromosomal abnormalities. Loss and gain of chromosomes represent one form of chromosome instability that is frequently a step in the development of cancer. Specifically, the researchers focused on chromosome 7 and a series of other chromosomal regions that are documented to be associated with MDS and AML. The researchers also evaluated the white blood cells from these patients to determine if both copies of each chromosome replicated synchronously or asynchronously. Asynchronous replication can also signal genomic instability and a higher risk of chromosomal abnormalities, and if G-CSF stimulates asynchronous chromosomal replication, if could predispose stem cell donors to higher cancer rates.
The outcomes of this research, however are clear. According to Betty Hirsch: “Contrary to the previously published data, our study concludes that G-CSF stimulation does not result in replication asynchrony or induce the atypical levels of abnormality for chromosome 7 or other chromosomes that have been associated with MDS and AML, and we expect that these results can be generalized to all chromosomes,” said Dr. Hirsch.
Jeffrey McCullough, MD, senior study author and Professor in the Department of Laboratory Medicine and Pathology at the University of Minnesota Medical School, added, “Furthermore, our data support the conclusion that G-CSF does not induce chromosomal instability through the PBSC mobilization process and remains a safe therapy for healthy stem cell donors.”