Physicians' Corner el pt

Familial CLL

Date: July 13, 2024

by Timothy G. Call, MD
Division of Hematology
Mayo Clinic, Rochester, MN

Insights, Advances and Research

Related Article:
Not the Worst Day of Your Life

Editor's Note: Dr. Tim Call is a hematologist/oncologist at Mayo Clinic, Rochester, MN and an Assistant Professor of Medicine at the Mayo Clinic College of Medicine. He has done much important work in the area of familial CLL and lymphoma, and is responsible for developing a database at Mayo Clinic on the familial incidence of B-cell malignancies including CLL, B-cell lymphomas and a few related diseases. You might recall his name as an author on the Mayo Best Practices article - Current Approach to Diagnosis and Management of CLL. More details are provided in his official Mayo Clinic profile. We are pleased that he has written this article addressed to the patient community. We strongly encourage that our readers register in one of the recommended databases when appropriate.

There is a rapidly increasing interest among patients and at academic medical centers in the topic of familial CLL and other lymphoproliferative disorders (LPD’s) such as Non-Hodgkin’s lymphoma, Hodgkin’s disease, hairy cell leukemia, etc. Five to ten years ago the literature contained a few scattered case reports of isolated families and most clinicians were not aware of a potential familial link in CLL or LPD’s. The following information provides some answers and identifies some advances regarding this issue. Hopefully, more answers will emerge from the cooperative efforts of patients, clinicians, geneticists and epidemiologists.

Over the last several years there have been a number of advances.

• Recognition that about 8% of CLL cases may have a familial component.
• That first degree relatives in families with at least 2 cases of CLL, or families with CLL plus an alternate LPD have an increased incidence of a small clonal population of mature B-lymphocytes that express characteristics similar to CLL. This is called monoclonal B Lymphocytosis (MBL). The significance of this finding is not yet known, but needs further study and longitudinal follow up. One important question is whether some individuals with MBL will eventually develop CLL.
• New molecular and genetic markers have been recognized in CLL. Although early studies do not show unique patterns of these markers in cases with a family history versus cases without a family history, it is important to keep looking for common genetic or environmental links. There should be a higher chance of finding them in these CLL families.

What should patients do about this?

If you are the only person in your family who has known CLL, there probably is nothing further that needs to be done. Your family members need to continue with routine medical and preventive health care. They should inform their physician of a CLL case in the family, so their family history section of the medical record will include it. They certainly may request that a CBC (complete blood count) be performed at their next check-up or if they have similar symptoms to yours.

If in your family there are at least 2 close relatives (parent, sibling, child, aunt or uncle, or 1st cousin) that have either CLL or another lymphoproliferative disease (such as non-Hodgkin’s lymphoma, Hodgkin’s disease and hairy cell leukemia), then other members of your family may have a higher risk of CLL or a LPD.  However, it is still likely that most members of your family will still not develop CLL, as CLL is an uncommon disease.

If this is the case, you may wish to consider the following:

• Your close family members will want to inform their primary medical provider of this family history so that it can be included in their medical history.
• If there are unexplained symptoms or concern, a CBC could be performed to look for CLL.  Also suspiciously enlarged lymph nodes should be evaluated and biopsied when appropriate.
• Be sure to inform your hematologist/oncologist that you do have another close relative with CLL or other LPD.

Is there any research being done and how could one get involved?

There is active research in the area of familial CLL/LPD. 

• First ask your hematologist/oncologist if they are involved in any familial research initiatives, if they are, consider enrollment in the study.
• If you are cared for at one of  the institutions participating in the CLL Research Consortium,  they have a tissue core bank where samples can be submitted and marked as familial to allow comparison studies.
• If you are cared for in an institution or clinic without a familial CLL research program, there are still options that are available.
• The Genetic Epidemiology Branch of the National Cancer Institute has a program for collecting blood and family histories on familial CLL families. Information can be obtained by calling 1-800-518-8474.
• Mayo Clinic, Rochester, MN, has a research study for families with either CLL or lymphoma. Individuals can either be seen at the clinic, or can fill out questionnaires and submit blood samples from their home facility. Information can be obtained by calling 1-800-610-7093.

What could I expect from enrolling in such a study?

The study of familial CLL or LPD’s is gaining momentum, but continues to be in an early stage. Although there are a number of chromosomal abnormalities associated with it, a specific genetic cause has yet to be identified. Therefore the most important thing now is identifying and collecting blood for special genetic analysis on as many CLL families as possible. At this stage, the studies are focusing on this task and then as the story unfolds hopefully candidate genes can be identified. These genes could provide answers as to causation and potential targets for future therapies. Although these studies may provide periodic updates and will publish their results in the medical literature, it is unlikely that they will provide individualized reports back to families.

Working with the CLL patient community, we hope that in the future we can develop methods of early identification of individuals at high risk of CLL and develop strategies for prevention and more non-toxic treatment.

Editor's Note:  You may be interested in two additional documents related to familial CLL. These documents are in pdf format. Clicking on the links will load them into the Adobe Reader plug-in for your browser.

Familial LPD Patient Information;
Referral Physician Information - Familial LPD.