Q&A: Genotype linked to unnecessary bone marrow biopsies
Click Here to Manage Email Alerts
Accounting for the benign rs2814778-CC genotype when considering a bone marrow biopsy could avoid unnecessary procedures, particularly in African American patients, according to findings published in JAMA Internal Medicine.
The rs2814778-CC genotype is common among African American patients and has been shown to lower white blood cell counts, Jonathan D. Mosley, MD, PhD, of the department of medicine at Vanderbilt University Medical Center, and colleagues wrote.
The researchers conducted a retrospective genetic association study to determine whether this genotype contributes to unnecessary bone marrow biopsies (BMB) for isolated low white blood cell counts. The analysis included 399 African American patients (mean age, 41.8 years) who underwent a BMB at three centers between Jan. 1, 1998, and Dec. 31, 2020.
Nearly 70% of patients who underwent a BMB carried the genotype. Almost all patients carrying the genotype (97%) had a history of low white blood cell counts compared with 67% of noncarriers. Also, 97% of genotype carriers received normal results compared with 55% of carriers who underwent biopsies due to other histories.
Healio Primary Care spoke with Mosley to learn more about the findings and their clinical relevance.
Healio Primary Care: What surprised you about the findings?
Mosley: Our hypothesis was that individuals who carry this genotype would be undergoing procedures that would not find any abnormalities because the genotype is not associated with any abnormalities. We looked at one particular outcome, bone marrow biopsies, which is the most rigorous workup for an abnormality of white blood cells. What caught us by surprise was how strongly the genotype was associated with having a biopsy for low white cells, and how strongly it was associated with having a biopsy that did not find any abnormalities.
Healio Primary Care: In what populations can this genotype be found?
Mosley: This is a genotype that just happens to be highly prevalent among one ancestral group. The genotype is very rare in non-Black individuals. Though the genotype leads to a racial disparity, it is not a race problem; it is a genetic problem.
Healio Primary Care: What is the clinical relevance of the findings?
Mosley: This is just one chapter in a long story. For many decades, we have observed that individuals who identify as Black had lower white cell counts. There is this stereotype that all Black people have lower white cell counts, but like all generalizations, this is inaccurate. About 10 or 15 years ago, researchers figured out that some African Americans, about 60%, have this genotype that causes low white cell counts. It’s not that African Americans have low white cell counts; it’s a subset of genotype carriers.
Healio Primary Care: What are the next steps for this research?
Mosley: The next step is to look at other risk groups.
Undergoing a bone marrow biopsy is really extreme. What most often happens to these individuals is their primary care doctor will say, let’s just repeat the lab work in a few weeks and see if your white cells change. They can keep undergoing repeat testing, which is not as invasive as a bone marrow biopsy, but is still an expensive process. The critical next step for this would be to say, if you have this genotype, it is not unusual to see a white cell count or neutrophil count less than the certain value. This is expected; don’t do any additional work-up for this patient.
We really need to find what is normal for those individuals, because what we have defined as the normal white blood cell range is based on reference groups that are largely Caucasian. That just doesn’t serve this group well.
Healio Primary Care: Besides reducing procedures like bone marrow biopsies and blood tests, could this affect other avenues of care?
Mosley: It has been shown that this causes African American individuals to have an increased risk of medications being stopped, because there is concern that the medications are lowering their white blood cell counts. This affects health care delivery in other domains.
Reference:
Mosley JD, et al. JAMA Intern Med. 2021;doi:10.1001/jamainternmed.2021.3108.