Dr. Susan Slager and colleagues presented this research at the American Society of Hematology Annual Meeting, which was held in December 2021 (ASH 2021)
Normal B-cells are polyclonal or different from each other. Cancer is made up of clonal or identical cells. Monoclonal B-cell lymphocytosis (MBL) is the common CLL precursor condition. It is characterized by a circulating population of clonal B-cells with an absolute B-cell count < 5×109/L, the normal count with clonal cells, and no evidence of enlarged lymph nodes, spleen, or low blood counts. These clonal B-cells are usually identical to the clonal B-cells in those with chronic lymphocytic leukemia (CLL). There are just fewer of them.
The condition can be further categorized into low or high-count MBL. Low count, MBL is defined as clonal B-cell <0.5×109/L or percent clonal B-cell count <85% out of total B-cell count. This study was focused strictly on patients with low count MBL (LC-MBL), in other words, normal lymphocytes count in blood but a small abnormal clonal population of b-cells found by a special screening test.
- Individuals were screened without a prior diagnosis of blood abnormality and came to Mayo clinic with some other unrelated (non-blood related) general medical condition(s).
- The subjects were followed for about nine years.
- Stored blood of these patients, specifically white blood cells, was screened with a special test known as an 8-color flow cytometry assay which is capable of detecting minute cancerous or clonal events in B cells population (B cells are a type of white blood cells, specifically the lymphocytes that when clonal can multiply and cause CLL).
- They screened 8,297 individuals 40 years or older and identified 1,326 (16%) patients with LC-MBL (patients with a cancerous event) and 6,651 (80%) controls (patients without a cancerous event).
- The rate of LC-MBL significantly increased with advancing age ranging from 3% among those 40-49 years, 10% among those 50-59 years, 15% among those 60-69 years, 23% among those 70-79 years, and 29% for those 80+ years.
- The investigators did not observe a significant difference in survival between those individuals with LC-MBL versus those without the condition controls despite a higher risk of infections in LC-MBL affected individuals.
- The prevalence (% of patients) of LC-MBL was higher in males (21%) than females (14%).
- Also, survival was longer among females with this condition than those without the condition. However, this was not observed in males.
- The researchers are now delving into the molecular events to understand which patient will or will not progress to CLL.
- It is important to note that not everyone who has MBL will go on to develop CLL.
- In the most extensive MBL screening study from Mayo clinic, LC-MBL was a common condition among adults 40 years or older, reaching a prevalence as high as 29% among individuals 80 years of age or older, however without adversely affecting survival.
- The survival among those with and without LC- MBL was similar, regardless of age at diagnosis.
- The longer survival in females with MBL versus controls requires further investigation.
- We look forward to learning more about this study as the clinical trial’s observation time progresses and more is known about the genetics of this condition.
In summary, this is telling us, among other things, clonal populations of B-cells similar to those seen in CLL are increasingly common as we age to the point where almost three out of ten individuals over 80 have LC-MBL. Yet, despite the presence of these cells, there is no impact on survival. Moreover, and surprisingly, females with the condition live longer than females without it!
Here is the link to the ASH 2021 abstract for more details.
Syed Ali Abutalib, MD
Co-Director, Hematology and Cellular Therapy Programs
Director, Clinical NMDP and CTCA Apheresis Programs
Cancer Treatment Centers of America, an Affiliate of City of Hope, Zion, Illinois
Associate Professor, Rosalind Franklin University of Medicine and Science
Founder, Advances in Cell and Gene Therapy Journal