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D Khaira

Publications and source records attributed to D Khaira.

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Declining lymphocyte counts following cytomegalovirus (CMV) infection are associated with fatal CMV disease in bone marrow transplant patients.

A previous pilot study conducted on 12 bone marrow transplant recipients suggested that detection of cytomegalovirus (CMV) in lymphocytes was associated with a drop in lymphocyte counts and death due to CMV disease. To test the association between decreasing lymphocytes and CMV-related death, we undertook a retrospective study of 332 CMV-infected patients transplanted between 1987 and 1990. The patients were divided into three groups: I = 170 patients who survived their infection and were alive at the time of the study; II = 103 patients who died of causes other than CMV infection; and III = 59 patients who died of CMV disease. Lymphocyte counts were analyzed during a 24-day period, starting 10 days before the day of first positive CMV culture (day 0). Lymphocyte counts were significantly lower in Group III from day 0 through day +14 (p < .001 vs. group I; and p = .002 vs. group II). Multivariate statistical analysis was used to adjust for other differences between the groups that might influence lymphocyte numbers. Average lymphocyte counts in patients who died of CMV disease decreased by an average of 35% after day 0. The differences in lymphocyte counts remained independent of the effects of acute graft-vs.-host disease (GVHD), time since transplant, transplant type, and high-dose steroid treatment. In summary, these data suggest that in some patients a drop in lymphocyte counts is a consequence of CMV infection associated with fatal CMV disease. Whether this can be attributed to direct infection of lymphocytes, a defective immune response, or some other mechanism remains to be determined.

Adult↗

Cytomegalovirus and marrow function.

Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. A proportion of patients with CMV infection also experience neutropenia. To investigate the possible role of CMV in the suppression of hematopoiesis, we have examined the effect of CMV on the growth of isolated myeloid progenitors and on the production of myeloid cells in the long-term bone marrow culture (LTMC) system. In these studies, various isolates of CMV were added either directly to cultures of progenitors or to LTMC established from normal CMV-seronegative donors. In the first system, myelosuppression is manifested by a reduction in the number of colonies that grow. In the second system, myelosuppression is manifested by a reduction in the number of myeloid cells produced and released into the culture supernatant. Analysis of the data observed indicated that myelosuppression could in some cases be attributed to direct infection of myeloid progenitors. In other cases stromal cells were infected. In the latter cases, myelosuppression was then caused by an alteration in cytokines produced by the stromal cells. These observations made in vitro raise the possibility that comparable mechanisms may be responsible for the myelosuppression observed with CMV infection in vivo. To pursue this possibility we proposed to detect the CMV genome in defined subpopulations of marrow cells isolated from infected patients. Given the technical restrictions imposed by the small sample size available from patient marrow aspirations, our initial attempts to develop on appropriate technique involved isolation of cells from CMV-seropositive normal bone marrow donors. Using the polymerase chain reaction we were able to amplify CMV DNA contained within marrow cells of some healthy CMV-seropositive marrow donors.

Bone Marrow↗