Lymphocytopenia as an unfavorable prognostic factor in patients with cytomegalovirus infection after bone marrow transplantation

Abstract

Sixty-three recipients of an allogeneic marrow transplant were screened for the occurrence of cytomegalovirus (CMV) infection and clinical parameters possibly predicting the development of CMV disease in a retrospective study. Blood and urine samples obtained from these patients were screened weekly after bone marrow transplantation (BMT) for the presence of CMV by polymerase chain reaction (PCR) and virus culture technique. Forty-six of the 63 patients studied were found to be CMV-positive by PCR technique in blood and urine samples at a median of 29 days after BMT. In 33 of these 46 patients, CMV could be cultured from urine samples and 16 of the 46 had culture-positive viremia. Twenty-eight of these 46 PCR-positive patients developed CMV disease. Whereas PCR assays showed an optimal negative predictive value and sensitivity for the development of CMV disease, their positive predictive value was 61% and could not be remarkably increased when culture-proven viruria (64%) and viremia (69%) were considered. Acute graft-versus-host disease (GVHD) grade 2 to 4 (P < .05), but not underlying disease, conditioning therapy, or GVHD prophylaxis, was associated with CMV infection. On day +49, a remarkable decrease (P < .001) in the lymphocyte count, as well as in the absolute number of CD4+, CD8+, and CD56+ lymphocytes, occurred only among the patients who later developed CMV disease. The decrease of all of these cell counts, but predominantly the CD4+ T cells, to less than 100/microL on day +49 after BMT showed a very high positive predictive value (100%) for the development of CMV disease in patients with PCR-proven viremia. Persisting CD4 lymphopenia after antiviral therapy was only observed in patients who finally died of CMV disease. Thus, immunophenotyping of the patients after BMT in addition to a highly sensitive virus detection assay might help to identify patients at high risk to develop CMV disease and indicate the need for additional adoptive immunotherapy.

Evaluation of an immunological score to assess the risk of severe infection in heart recipients

“…CD4 T cells are affected by induction protocols, thus predisposing patients to opportunistic infections after solid organ and bone marrow transplantation . CD4 lymphopenia is also a risk factor for bacterial infection in other models of secondary immunodeficiency .…”

Human CMV-specific T-cell responses in kidney transplantation; toward changing current risk-stratification paradigm

“…Despite that humoral immunity through the presence of hCMV‐specific IgG antibodies is considered the gold‐standard biomarker determining the history of viral infection, it is well accepted that cellular immunity, particularly memory/effector CD4 + and CD8 + T cells, is considered to be crucial for protection from hCMV infection. In fact, in the human system, there are relevant examples showing the predominance of T‐cell responses for the control of hCMV; both T‐cell lymphopenia and impaired lymphoproliferative responses to hCMV have been demonstrated as risk factors for hCMV disease , and more illustrative, adoptive transfer of hCMV‐specific T‐cell clones after allogeneic stem cell and solid organ transplantation (SOT) has provided reasonable indirect evidence demonstrating the importance of hCMV‐specific T‐cell responses for protection against viral replication .…”

The significance of cytomegalovirus viremia at day 100 or more following allogeneic hematopoietic stem cell transplantation

“…CD8 + cytotoxic T lymphocytes have been identified as the main effector cells against CMV , including late CMV reactivation . CD4 + T cells have also been associated with controlling CMV reactivation after HSCT , and in a prospective cohort study, a CD4+ T‐cell count < 50 cells/mm 3 at three months post‐transplant was a risk factor for the development of late CMV disease . Others, however, have shown that measuring CMV‐specific CD8+ T‐cell numbers and CD4+/CD8+ function by HLA‐peptide tetramer staining has not been predictive of late CMV risk .…”

“…Ozdemir et al. found that the incidence of late CMV was approximately twofold higher among patients with lymphoid compared to myeloid malignancy and in that study as well as others , lymphopenia predicted the occurrence of late CMV. We found that higher day 100 lymphocyte counts were protective against late CMV in univariable analysis, and there was a trend toward hypogammaglobulinemia also conferring risk of late CMV infection.…”