Correlations of hematological parameters with bone marrow findings in chronic lymphoproliferative disorders associated with hepatitis viruses

Abstract

Background: Hepatitis B and C viruses' infections are often associated with hematological disorders in evolution, suggesting that these viruses have a tropism for peripheral blood and/or bone marrow cells.

Aim: To analyze the hematological parameters and bone marrow findings in a group of patients diagnosed with chronic lymphoproliferative disorders (CLD) and hepatitis viruses B, C, D infections, which were included in the research grant (acronym LIMFO-VIR) between December 2007 and May 2010 in the Hematology Department of the Emergency University Hospital of Bucharest.

Methods and results: Patients were diagnosed by using immunopathology according to the WHO criteria. The analyzed group included 42 patients (both sexes), with the mean age of 60,35 years. The most frequent hematologic disease was non-Hodgkin's lymphoma 30/42 (71,42%), followed by chronic lymphocytic leukemia (16,66%) and Hodgkin's lymphoma (7,14%). Hepatitis viruses were distributed: 17/42 (40,47%) patients with HBV, 22/42 (52,38%) with HCV and 3/42 (7,14%) had a double/triple association of viruses. Most of the patients had an indolent type of disease - 27/42 (64,28%), whereas 15/42 (35,71%) had an aggressive one, pattern found both in the HBV and HCV infected groups. An abnormal bone marrow result was revealed in 32/42 (76,19%) patients, 19 (59,37%) of them being HCV infected. Myelodysplasia was found in 6/42(14,28%) patients, the majority being HCV infected, all having an indolent form of CLD. The antiviral therapy did not influence the hematological parameters (no significant differences were found between the groups with/without an antiviral therapy).

Discussions: Patients with hepatitis virus infections may associate neutropenia and thrombocytopenia; the mechanisms are thought to involve hypersplenism, autoimmune processes and antiviral therapy. We excluded the influence of chemotherapy, as the study was performed before the treatment. In our group, patients whether HBV or HCV infected, presented an isolated cytopenia. The abnormal bone marrow cellularity (increased or decreased) and dysplasia were found especially in the HCV group. There are studies showing no association between myelodysplasia and hepatitis viruses; others found a strong relation of these. One of the mechanisms of myelodysplasia could be a dysregulation of the immune system. Conclusions. Bone marrow/peripheral blood features correlate with the type of viral infection and HCV is more prone to develop additional hematological changes than HBV. The degree of bone marrow involvement by CLDs influences these features. We considered mandatory to perform a bone marrow analysis at the diagnosis of CLDs to stage and to establish if other bone marrow changes were present, a crucial aspect for therapy and outcome of the disease. The association between the hepatitis viruses - myelodysplasia- autoimmunity seems to have a role in the lymphoproliferative disorders etiology.

Abbreviations: CLD - chronic lymphoproliferative disorders; NHL- non-Hodgkin's lymphoma, CLL- chronic lymphocytic leukemia, HL- Hodgkin's lymphoma, MDS - myelodysplastic syndrome, AML - acute myeloid leukemia.

Keywords: chronic lymphoproliferative disorders; cytopenia; hepatitis viruses; myelodysplasia.

Fig. 1

Hepatitis viruses’ distribution: HCV infection had a higher frequency compared to HBV infection; the mean age of patients diagnosed with HCV infection was significantly increased compared to the HBV group

Fig. 2

Distribution of CLDs according to the viral infection: non-Hodgkin’s lymphoma was predominant in the studied group, mainly associated with the HCV infection

Fig. 3

The association between the histological type of CLD and hepatitis viruses: in all cases of infection with hepatitis viruses B, C or mixed infection, the indolent form of the hematological disease was more frequent

Fig. 4

The association of cytopenias and hepatitis viruses: isolated cytopenia was the most frequent CBC abnormality, associated mainly to HCV infection; pancytopenia was found in only one patient which had HBV infection

Table 1

Clinical and laboratory characteristics (mean values)

Fig. 5

The presence of the bone marrow dysplasia in patients with lymphoproliferative condition and hepatitis viruses: although signs of dysplasia were found in only few patients, almost all (5 of 6 patients) had HCV infection; all the cases presented an indolent form of CLD

Fig. 6

Bone marrow abnormalities and hepatitis viruses: HCV is more frequently found in patients with bone marrow changes compared to HVB

Table 2

Cytopenia’s association with bone marrow findings

Table 3

Hematological parameters correlated to viral infection

Table 4

Correlations of hematological parameters and antiviral therapy