Peripheral blood leukocyte counts in cytomegalovirus infected heart transplant patients: impact of acute disease versus subclinical infection

BACKGROUND: Cytomegalovirus (CMV)-associated leucopenia in heart transplant patients is poorly characterized. METHODS: We conducted a retrospective analysis of timing, degree, and type of leukopenia in four groups of patients: cases (n=20); controls (n=20); subclinical early infection (n=21), and subclinical late infection (n=22). In the cases, white blood cells (WBC) count at diagnosis was compared to prediagnosis; and cases were compared to controls. Subclinical cases (early and late) were identified by measurement of CMV DNA in peripheral blood mononucleocytes, and WBC was compared to those of the cases and controls. RESULTS: First, in human heart transplant recipients the total leukocyte count decreased prior to the time of diagnosis of CMV disease: cases: 5.4+/-2.1 x 10/microL vs. 3.7+/-2.1x10/muL (P<0.01); subclinical early: 8.1+/-4.1 x 10/microL vs. 6.9+/-1.6 x 10/microL (P<0.01). Second, the leukocyte populations most reduced during CMV disease are the neutrophils: 4.4 x 10/microL (78%) to 2.5 x 10/microL (69%) (P<0.05), and monocytes 0.6 x 10/microL (11%) to 0.3 x 10/microL (7.5%) (P<0.05). Third, the reduction in leukocyte count that occurs during CMV disease appears to be independent of immunosuppressive therapy (using cyclosporine A, mycophenolate mofetil, or azathioprine and prednisone). Finally, subclinical CMV infection in stable long-term heart transplant patients without disease is unassociated with a reduction in the leukocyte count. CONCLUSIONS: Aside from implications for early diagnosis, CMV-associated decrease in monocytes is important because viral infections like Epstein-Barr virus cause monocytosis. The absence of leucopenia in subclinical late infections is a new important finding.