Title of the Research Project:
“Understanding and Targeting Hematopoiesis in CLL with the Use of Probiotics”
Research Project Summary:
Clonal Hematopoiesis (CH) occurs when a group of blood cells in the body all come from a single abnormally mutated cell that has a different genetic pattern compared to the rest of the blood cells in the body. This is a common occurrence that can happen with aging in up to 30% of older adults. CH causes blood cells to release molecules that promote inflammation, and it is thought that chronic inflammation supports an environment where these abnormally mutated cells can reproduce quickly and survive longer than normal. CH is associated with an increased risk of blood cancers, including chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It is also associated with an increased risk of heart failure, stroke, chronic kidney disease, gout, chronic obstructive pulmonary disease, and poor outcomes with COVID-19 infection. Studies have shown that those who have CH have a shorter survival time because of all the comorbid conditions that are associated with it. Additionally, it is believed that a certain bacteria in the gastrointestinal tract of those with CH produces a molecule called ADP-heptose, which leads to inflammation in the gut. Some researchers believe that the make-up of the gut microbiome (which is the collection of fungi, bacteria, and viruses that live in the gut) may influence many aspects of overall health. Probiotics have certain strains of bacteria in them, and when taken they can change the microbiome. Dr. Byrd hopes that giving probiotics to CLL / SLL patients will cause a change in their gut microbiome which could impact the amount of inflammation and improve overall health.
About the Award Recipient, Dr. John Byrd:
John Byrd, MD, is an internationally known researcher and clinical specialist in leukemia and other hematologic malignancies who serves as the Chair of the Department of Internal Medicine at the University of Cincinnati. Dr. Byrd received his medical degree from the University of Arkansas for Medical Sciences. His education continued in internal medicine and hematology and oncology at Walter Reed Army Medical Center and Johns Hopkins University before moving to Columbus to join the faculty at Ohio State. Dr. Byrd has over 600 publications on leukemia and experimental therapeutics research. He runs a highly translational laboratory focused on CLL and drug development in hematologic malignancies, and he has been part of the successful development of multiple therapeutics for CLL and SLL.
Why Is Research About Hematopoiesis in CLL / SLL Needed?
The microbiome in the gut and how it can drive illness is a popular area of research. Many scientists hypothesize that changing the microbiome in the gut can possibly improve many health conditions. Research on probiotics is important because it is believed that they have the potential to improve overall health by boosting the immune system, reducing inflammation, and potentially aiding in the prevention of chronic diseases. It is important for CLL / SLL because it is a cancer of the immune system, and some research suggests probiotics can positively influence the immune system by regulating immune responses and potentially reducing inflammation throughout the body. Some probiotics may even produce compounds that inhibit the growth of harmful bacteria, potentially aiding in infection prevention. CH is just starting to be associated with many different health conditions, and scientists are just now understanding that it drives inflammation. However, it is not well known if anything can be done to lower the amount of inflammation or get rid of the CH. If CH and inflammation can be lowered, it is important to understand what the implications are and if it will improve overall health.
When Researching the Use of Probiotics in CLL / SLL, What Are the Challenges?
One of the biggest challenges is that there is minimal research being done on integrative approaches in CLL / SLL due to a lack of funding. Also, not all probiotics are created equal, and they are not regulated by the FDA. When choosing the brand of probiotic to use for this study, knowing the concentration and the strain of the probiotic that is being administered will be critical. Since probiotics are considered to be over-the-counter supplements and not drugs, there is unfortunately only a modest amount of quality assurance. It may be a challenge to ensure that the bacterial strains are consistent from one bottle to another.
Who Is Eligible for This Study?
Participants from the University of Cincinnati will be eligible for this study if they have CLL or SLL and it has been determined that they have CH.
What Interventions Will Be Used?
This research proposal’s interventions will include the administration of high-quality probiotics to CLL / SLL patients for 90 days who have CH with increased ADP-Heptose levels present.
What is the Design of the Study?
Dr. Byrd plans on sequencing the DNA in the stool samples to measure what different types of bacteria are present in the gut after probiotic administration. He will first obtain stool samples from all the study participants prior to probiotic administration. Then he will administer the high-quality probiotics to study participants for 90 days. During that time stool samples will be collected and analyzed again at 30 days, 60 days, and 90 days after initial administration. Stool samples will then be analyzed one last time at the 180-day mark.
How Will the Findings Be Used?
If administering probiotics results in no long-term change of the microbiome in the gut, Dr. Byrd will be able to conclude that the administration of probiotics does not impact inflammation. However, if he does see changes in the bacterial make-up of the stool samples, and especially if he finds there was a simultaneous decrease in the amount of CH cells and inflammatory markers, then the data gained from his study will hopefully lead to a much larger study on the subject. Ultimately Dr. Byrd’s pilot study will be used to determine if there is evidence to prompt a larger, more extensive research study on this subject in the future.
Please watch the interview between CLL Society’s Director of Scientific Affairs and Research, Robyn Brumble, RN, MSN and John Byrd, MD.
What Is the Goal of CLL Society’s Integrative Medicine Award?
This research award supports an exceptionally innovative research project that aims to provide an understanding of the mechanistic basis, or clinical outcomes related to the use of integrative medicine therapies, specifically for those living with CLL / SLL. The award is aimed towards exploring ideas that incorporate an integrative approach to addressing the many health challenges of those living with the disease, to help address gaps that exist in current research, and build a strong evidence base to improve quality of life for those living with the disease.
This 2024 Integrative Medicine Award was made possible through the generosity of Vigyan Singhal.
CLL Society invites you to read more about CLL Society’s Research Program. CLL Society is one of the only blood cancer organizations whose research program is dedicated solely to funding CLL / SLL research. CLL Society relies heavily on generous donations from our community to fund this important work.
