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ASH 2021: Increased Risk for Serious Infections Linked with Monoclonal B-Cell Lymphocytosis

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Patients with monoclonal B-cell lymphocytosis (MBL), a precursor to chronic lymphocytic leukemia (CLL), were at increased risk of severe infections, according to an analysis of records from participants collected in the Mayo Clinic Biobank.

Coauthor Susan L. Slager, Ph.D., leader of the Mayo Clinic B-cell lymphoma family registry analysis, presented the findings at the 2021 ASH Annual Meeting. The data further showed that individuals with another common premalignant hematological condition, monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma, were also more likely to develop severe infections when compared to the healthy control group. Investigators also analyzed patients with clonal hematopoiesis (CH), a risk factor for another blood cancer, myelodysplastic syndromes but did not find an association between CH and serious infections (hazard ratio [HR], 1.15; 95% CI, 0.71-1.87).

MBL is a laboratory abnormality characterized by small clonal B-cell populations in the peripheral blood of otherwise healthy people. About 5% of those older than 40 have this presence of small clonal B-cell populations, usually at very low levels.

MBL is defined as either low count or high count:

  • Low count MBL (<0.5 X 109/L clonal B cells)
  • High count MBL (≥5 X 109/L clonal B cells)

Approximately 1% to 2% of patients with high-count MBL, defined as B-cell populations in the peripheral blood greater than 5 x 109/L, develop a type of CLL that requires treatment annually.

The median age for patients in this analysis was 68 years. Brian T. Hill, MD, PhD, Director of the Lymphoid Malignancies Program and a staff physician at the Cleveland Clinic Taussig Cancer Institute, interviewed Dr. Slager. She reviewed the data and noted that the prevalence of MBL increases with age. She added that the condition is common, with approximately 40% of people older than 90 having MBL, but overall survival is not affected.

Before digging deeper, Dr. Sameer Parikh shares some prior research that can provide a background to understanding MBL in this earlier interview with Dr. Pagel from ASH 2019, quoted below: 

“What we’re trying to do with our overall research program is to see if there’s any clinical significance of having MBL even though you may not progress to CLL. [Are] there any other clinical issues that you may encounter if you have this precursor condition? What we’re finding is that with overall survival, you seem to have the same or similar survival rate as an individual who doesn’t have this condition. But we’ve shown in the past that if you have this condition, you have an increased risk of getting hospitalized due to infections. That was one of our first findings of clinical significance of having MBL.”

Returning to the more recent data, investigators at the Mayo Clinic in Rochester, Minnesota, analyzed records from 407 adults who contributed to the Biobank, a large-scale biorepository of peripheral blood samples collected from July 2009 to June 2015.

  • Eighty-one (19.9%) patients were positive for MBL
  • 59 (14.5%) were positive for MGUS (monoclonal gammopathy of undetermined significance)
  • 104 (25.6%) were positive for CH (clonal hematopoiesis)

Eighty patients developed 97 serious infections, defined as an infection requiring hospitalization, from the time of sample collection through December 31, 2020, or the date of death.

  • When investigators further evaluated the association between each condition, they found no evidence of a link between
    • Prevalence of CH and risk for MBL (odds ratio [OR], 0.79)
    • Prevalence of CH and risk for MGUS (OR, 1.24)
    • Prevalence of MGUS and risk for MBL (OR, 1.32)

TAKEAWAYS

  • There was no apparent connection between the presence of MBL, MGUS, or CH and overall survival.
  • Compared with healthy controls, patients with MBL or MGUS were at increased risk for severe infection.
    • MBL (HR, 1.75; 95% CI)
    • MGUS (HR, 1.75)
    • There was no association between CH and infection risk.
  • The most common infections were urinary tract (20), pneumonia (14), and cellulitis (14), which is a common but, potentially serious bacterial skin infection.
    • Patients with more than one condition were at even greater risk for infections
    • There was a 35% greater chance of infection for those who had one condition (HR, 1.35)
    • The risk of infection was more than 2.5 times greater for those who had two or more conditions (HR, 2.58)
  • MGUS is a precursor condition, and CH is currently a risk factor. However, it is possible to harbor either without ever developing cancer.

“Remarkably, one of the things we found in our study was that almost half of the individuals had one of these conditions,” Slager said. “Our study is a little bit selected because of the MBL screening, but it’s still pretty remarkable how common it was to have at least one.”

You can read the full ASH 2021 abstract here: Relationship and Susceptibility to Serious Infections Among Monoclonal B-Cell Lymphocytosis (MBL), Monoclonal Gammopathy of Undetermined Significance (MGUS), and Clonal Hematopoiesis (CH) Premalignant Conditions.

Please enjoy this interview between Dr. Susan Slager and Dr. Brian Hill.

Braxton Cole has more than 20 years of experience as a journalist, including over a decade covering hematology/oncology for various outlets.