TRAINING and EDUCATION
You Make the Call
Each month in “You Make the Call,” we pick a challenging clinical question submitted through the Consult a Colleague program
and post the expert’s response, but we also want to know what you would do. Send in your response to next month’s clinical
dilemma and see how your answer matches up to the expert’s in the next print issue.
This month, Kanti R. Rai, MD, discusses familial chronic lymphocytic leukemia.
Clinical Dilemma:
I have a patient with a strong family history of chronic lymphocytic leukemia (CLL) who was recently diagnosed with
CLL. Her mother and brother have CLL as well. What is the status of familial CLL? Has a gene been identified yet?
Expert Opinion
Kanti R. Rai, MD
Joel Finkelstein Cancer Foundation Professor of Medicine and Professor of Molecular Medicine
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Hempstead, New York
Virtually all clinicians who treat chronic lymphocytic
leukemia (CLL) have observed that family members of
patients with this disease are also found to have CLL in
greater frequency than can be expected in the general
population. Your patient, who was recently diagnosed
with CLL, reports that her mother and brother have
CLL. Such family occurrences of CLL or any other
lymphoproliferative disorders (LPDs) have been re-
ported in 18 percent of patients with CLL. This high
incidence is clearly suggestive of a strong inherited
genetic component in the causation or development
of CLL. 1 However, an oncogene associated with fami-
ly occurrence of CLL has not been discovered.
Several investigators have found a few CLL suscep-
tibility loci, but a clearly heritable risk factor remains
unidentified. A meta-analysis of six genomewide associ-
ation studies provided single-nucleotide polymorphism
genotypes and nine risk loci (which map to areas of B-cell
development). These are very exciting observations but
account for only a fraction of cases of familial CLL. 2
Using a combination of data from a Norwegian cancer
registry and a questionnaire, Geir E. Tjønnfjord, MD,
PhD, and co-authors found a sixfold increased risk of
CLL among family members of persons known to have
CLL. 3 Another comprehensive study using data from the
Swedish Cancer Registry reported an 8.5-fold increased
risk of CLL (and 1.9-fold increased risk of LPDs) in
first-degree relatives of patients with CLL. 4
We also should include an additional public health-
related condition called monoclonal B-cell lymphocytosis,
a pre-CLL state somewhat analogous to monoclonal gam-
mopathy of unknown significance and multiple myeloma,
which also occurs more frequently in family members
of persons known to have CLL. With the current rapid
Consult a Colleague
Through ASH
Consult a Colleague is a service for ASH
members that helps facilitate the exchange
of information between hematologists
and their peers. ASH members can
seek consultation on clinical cases from
qualified experts in 11 categories:
• Anemias
• Hematopoietic cell
transplantation
• Hemoglobinopathies
• Hemostasis/thrombosis
• Lymphomas
• Lymphoproliferative disorders
• Leukemias
• Multiple myeloma & Waldenström
macroglobulinemia
• Myeloproliferative neoplasms
• Myelodysplastic syndromes
• Thrombocytopenias
pace of investigations, I am optimistic that we will soon
have a definitive answer to your question.
REFERENCES
1. Slager SL, Caporaso NE, de Sanjose S, Goldin LR. Genetic susceptibility to chronic lymphocytic
leukemia. Semin Hematol. 2013;50:296-302.
2. Law PJ, Berndt JI, Speedy HE, et al. Genome-wide association analysis implicates
dysregulation of immunity genes in chronic lymphocytic leukaemia. Nat Comm. 2017;8:14175.
3. Tjønnfjord GE. Familial occurrence of chronic lymphocytic leukaemia in Norway. J Norw Med
Assoc. 2012;132:2060-3.
Assigned volunteers (“colleagues”) will
respond to inquiries within two business
days (either by email or phone).
Have a puzzling clinical dilemma?
Submit a question, and read more
about Consult a Colleague volunteers at
hematology.org/Clinicians/Consult.aspx
or scan the QR code.
4. Goldin LR, Björkholm M, Kristinsson SY, et al. Elevated risk of chronic lymphocytic leukemia
and other indolent non-Hodgkin’s lymphomas among relatives of patients with chronic
lymphocytic leukemia. Haematologica. 2009;94:647-53.
Next Month’s Clinical Dilemma:
I have a 36-year-old male Samoan patient with glucose-
6-phosphate-dehydrogenase (G6PD) deficiency (World
Health Organization class III), chronic tophaceous
gouty arthropathy, and chronic renal insufficiency sec-
ondary to prolonged nonsteroidal anti-inflammatory
drug use. His baseline creatinine is 2.67 mg/dL and
his glomerular filtration rate is 27. He has a white
blood count of 13.8, hemoglobin level of 11.6 g/dL,
hematocrit level of 35.1 percent, and a platelet count
of 438×10 9 /L. He is experiencing extreme pain and
difficulty walking due to gouty arthropathy and has
been disabled for eight years.
ASHClinicalNews.org
His rheumatologist would like to institute peglot-
icase, a pegylated uric acid–specific enzyme, which
is a known cause of hemolysis in patients with G6PD
deficiency. The patient wants to try this agent to
reduce his extensive, painful tophi. I am looking for
other opinions about the possibility of administering
pegloticase in a hospital setting with transfusion
support if brisk hemolysis should occur.
How would you respond? Email us at
[email protected]. ●
* If you have a request related to a
hematologic disorder not listed here,
please email your recommendation to
[email protected] so it can be
considered for addition in the future.
DISCLAIMER: ASH does not recommend
or endorse any specific tests, physicians,
products, procedures, or opinions, and
disclaims any representation, warranty, or
guaranty as to the same. Reliance on any
information provided in this article is solely
at your own risk.
ASH Clinical News
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