Value of Additional CD19 Lymphocyte Counts for the Detection of B-CLL in a Primary Health Care Laboratory

Background: B-cell chronic lymphocytic leukaemia (B-CLL) is the most common type of lymphoma in the Western world and is often diagnosed by coincidence in patients with an increased absolute lymphocyte count (ALC). Although immunophenotyping is advised for all patients with an increased ALC of unknown aetiology, referral for immunophenotyping in all patients with increased ALC will result in high costs and inconvenience for patients, since a considerable number of patients with increased ALC has no B-CLL or other malignancy. On the other hand, early haematological consultation at diagnosis is becoming more important, since initiation of treatment of B-CLL is changing from a symptom-based strategy towards a strategy based on biological markers. In this context, an additional CD19 count might be a valuable laboratory test to reduce unnecessarily referrals and to facilitate early haematological consultation of patients with B-CLL.

Aim: To investigate the value of an additional CD19 count in detecting B-CLL in patients with increased ALC in a primary care laboratory.

Methods: In the period from March 2001 until October 2006, a CD 19 lymphocyte count was performed in all patients, living in a previously defined geographic area, aged ≥ 40 years with an abnormal White Blood Cell count (WBC), defined as absolute lymphocyte count (ALC) ≥ 6.0x10⁹ cells/L, relative lymphocyte count (RLC) ≥ 60% or atypical lymphocytes (AL) ≥ 2+. WBC’s were requested by general practitioners for any reason not further specified. Patients with positive EBV or CMV serology were excluded. CD19 lymphocyte counts were classified as negative (<1.0x10⁹/L) or positive (≥1.0x10⁹/L). In case of a positive test, referral to a haematologist was advised. A geographic area in which the contingency areas of SALTRO and the referral hospitals overlapped was based on postal codes in order to link patients in whom a CD19 lymphocyte count was performed to newly diagnosed B-CLL patients in the hospitals. In October 2007, all cases of B-CLL in this area were identified by a stepwise search-strategy with a survey among general practitioners, including two postal questionnaires and a telephone reminder and by consultation of three different databases. All data were collected anonymously and CD19 lymphocyte count cases and B-CLL cases were cross-referenced by postal code and date of birth.

Results: A CD19 lymphocyte count was performed in 543 patients of 199,108 (0.3%) patients in whom a WBC was performed; 229 (42%) were positive and 314 (58%) were negative. In total, 120 patients with a B-CLL were identified; 119 in the positive test group en 1 in the negative group. This resulted in a sensitivity and Positive Predictive Value (PPV) of 99% (95%CI 97.9–99.7) and 52% (95%CI 47.6–56.2) respectively and specificity and Negative Predictive Value (NPV) of 74% (95%CI 70.1–77.7) and 100% (95%CI 98.7–100) respectively. This resulted in a Number Needed to Screen (NNS) of 1.9. The AUC for CD19 count and ALC, 0.92 (95% CI 0.90–0.94), was significantly higher than the AUC for ALC only; 0.85 (95% CI 0.81–0.88). The PPV of ALC only, 34% (118/348) was significantly lower compared to the PPV of the CD19 count and ALC combined; 52% (119/229).

Conclusion: CD19 count is a valuable laboratory test in detecting B-CLL in a primary care setting with a high sensitivity and PPV. The CD19 count is superior to ALC only. Introduction of a CD19 count in a primary health care laboratory has additional value in the selection of patients with increased ALC for referral to haematologists. The value of early detection strategies for B-CLL, such as CD19 counts in a primary health laboratory, will depend on the outcome of ongoing studies of treatment, based on new biological markers indicative of a poor prognosis, in early stages of B-CLL.