Utility of Peripheral Blood BCR-ABL Mutation Analyses in Patients with Unexplained Neutrophilic Leukocytoses. Incidence of a Positive Test and Its Clinical Correlates

In patients with chronic unexplained neutrophilic leukocytoses (UNL), underlying Chronic Myeloid Leukemia (CML) is a concern. In these patients, peripheral blood BCR-ABL mutation analyses using fluorescent in situ hybridization (FISH) is often performed to investigate for CML. Diagnostic yield of this test, in patients presenting UNL and especially in those with mild leukocytoses is uncertain.

To establish the overall incidence BCR-ABL mutation in patients with UNL using peripheral blood FISH analyses. To determine the incidence within subgroups based on severity of leukocytoses. To explore the association between a positive test and the presenting clinical and laboratory features.

We performed a retrospective chart review (2000–2010) of adult patients referred to the hematology service at the Dallas Veterans Administration Medical Center for evaluation of UNL. All patients had undergone, peripheral blood BCR-ABL mutation analyses by FISH. Neutrophilic leukocytoses were defined as a white blood count (WBC) above 11 × 10⁹/L along with an absolute neutrophil count (ANC) greater than 7 × 10⁹/L. It was considered unexplained, if it persisted on repeat testing and the referring physician deemed its etiology as uncertain. The primary end point was incidence of BCR-ABL positivity in patients with UNL. Incidence of BCR-ABL positivity within subgroups based on degree of WBC elevation defined as mild (11–20 × 10⁹/L), moderate (>20–50 × 10⁹) or severe (>50 × 10⁹) was also calculated. Univariate and multivariate regression analyses of various laboratory and clinical features was performed to identify any confounding variables.

The median time from discovery of leukocytoses to the performing the test was 1545 days (n=285). 26 (9.1%) patients were found to be positive for BCR-ABL (n= 286). Majority had mild leukocytoses (n=202). The incidence increased with the severity of leukocytoses. Mild = 4/202 (2%), moderate = 9/62 (14.5%), severe = 13/22 (59.1%). On univariate analyses, a positive test was associated with presence of an elevated LDH (OR=107 CI 14.17–809.99), myeloid left shift (OR=107 CI 14.17–809.99) and hepatosplenomegaly (OR 3.87 CI 1.57–9.54). On multivariate regression, the presence of a myeloid left shift was strongly associated with a positive test (OR=67.20 CI 8.36–540.36). Myeloid left shift was seen in 3/4 (75%) of patients with a mild leukocytoses and positive test for BCR-ABL,

In patients with UNL, peripheral blood FISH for BCR-ABL mutation should be restricted to those with moderate to severe leukocytoses. Incidence of BCR-ABL is especially low (2%) in patients with mild leukocytoses (<20 × 10⁹/L). In these patients BCR-ABL testing should be limited to those with an unexplained myeloid left shift.

No relevant conflicts of interest to declare.