Introduction: The standard criterion for diagnosing chronic lymphocytic leukemia (CLL) is clonal lymphocytosis of >5×10 9/L. Cases of CLL with normal lymphocyte count have been diagnosed by flow cytometry based on the presence of clonal CD19+/CD5+/CD23+ cells. Therefore, it is not unexpected that a proportion of patients with borderline lymphocytosis (>3.5 and <5.0x10 9/L) will have CLL. The aim of our study is to establish the prevalence of CLL in patients with borderline “4.0 to 5.0x109/L” lymphocytosis in the adult population (age >40 years) seen in community practice.

Methods: Using flow cytometry we analyzed a total of 157 sequential peripheral blood samples collected from patients older than 40 years presented with borderline lymphocytosis (4 to 5 x109/L). Majority of these patients (#106) were detected incidentally during routine CBC and 51 samples were submitted to rule out lymphoproliferative diseases.

Results: Forty of the 157 (26%) patients had clonal B-cell disease meeting the criteria for chronic lymphoproliferative disease. The disease was classified as CLL in 35 patients (87.5%), hairy cell leukemia in 1 patient (2.5%), Waldenstrom’s macroglobulinemia in 1 patient (2.5%) and marginal zone B-cell lymphoma in 3 patients (7.5%). This data suggests that patients older than 40 year with lymphocyosis >4x10 9/L have high probability of having chronic lymphoproliferative disease. This disease could be other than CLL and should be thoroughly investigated.

DISCUSSION: In our study the prevalence of low grade lymphoproliferative disorders in patients with borderline lymphocytosis (4–5 x109/L) above the age of 40 is 26%. This number may be positively skewed considering our selection criteria (including a subset of patients retrospectively included).

Currently, there is no data to support that early intervention is beneficial for CLL, even for patients with unfavorable prognosis (e.g., those with ATM and P53 deletions). Early diagnosis of CLL will create more opportunity to study the disease in its early stages.[Shanafelt TD, Geyer SM, Kay NE: Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL. Blood. 2004 Feb 15;103(4):1202–10. Epub 2003 Oct 23. Review.], [ Hamblin TJ: Achieving optimal outcomes in chronic lymphocytic leukemia.

Drugs. 2001;61(5):593–611
. Review.]. Since lymphocyte doubling time (LDT) is a prognostic factor (the prognostic utility of LDT is most important for patients with early stage disease who typically are treated by watchful waiting [ Shanafelt TD, Call TG. Current approach to diagnosis and management of chronic lymphocytic leukemia. Mayo Clin Proc. 2004 Mar;79(3):388–98. Review. ] ). early diagnosis may help to better segregate low from high-risk patients. Finally, in today’s cost containment pressures, it is beneficial to have an expectation for the cost/benefit ratio of performing a test. Knowing the prevalence of disease at decision limits may help us to better justify establishing testing guidelines.

Topics:
lymphocytosis, lymphoproliferative disorders, chronic b-cell leukemias, chronic lymphocytic leukemia, early diagnosis, flow cytometry, hairy-cell leukemia, lymphoma, mucosa-associated lymphoid tissue, marginal zone b-cell lymphoma, prognostic factors

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2005, The American Society of Hematology
2005
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