Cytomegalovirus Seronegative Heart Transplant Recipients: DISCUSSION

10 Apr

We treated all CMV seronegative recipients irre­spective of donor serology with anti-CMV immuno­globulins from the day of transplantation. Arguments for this strategy were that the CMV serology of the donor is not always available at the time of transplan­tation and that CMV unscreened (although bufly coat poor) blood is used during open heart surgery. More­over, in the majority (65 percent) of the CMV seroneg­ative heart transplant recipients rejections are treated in the first three months after transplantation, and therefore, these patients will become high risk for CMV disease.

Based on the data from the literature, we expected to find a high incidence (82 percent) of symptomatic CMV infection in CMV seronegative heart recipients from a CMV seropositive donor. In the globulin- treated patients, we found a much lower (13 percent) incidence of CMV disease. Only one patient had to be treated with DHPG, and none of the seronegative patients died because of CMV infection. However, the incidence of CMV excretion was high (50 percent) in these patients. The incidences of CMV isolation (39 percent) and related disease (10 percent) in the nonglobulin-treated CMV seropositive recipients were comparable with those in the globulin-treated CMV seronegative heart recipients from a seropositive do­nor. In the untreated CMV seronegative recipients from a CMV seropositive donor, the incidence of CMV disease was 50 percent. These observations suggest that passive immunization with anti-CMV immuno­globulin can prevent or mitigate symptomatic CMV infection, and thus induces the same protection against CMV disease as natural acquired anti-CMV resistance. However, virus replication was not reduced by passive immunization, and prophylaxis was only temporarily effective as can be learned from the patient with symptomatic disease after the anti-CMV IgG titer had decreased to pretransplantation levels. The efficacy of prophylactic globulin treatment to reduce CMV dis­ease but not infection is in accordance with the studies in CMV seronegative renal transplant recipients from a seropositive donor.
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In CMV seronegative heart recipients from a sero­negative donor, the incidence of isolation was much lower as compared with that in CMV seronegative recipients of a CMV seropositive allograft (6 percent vs 50 percent). In theory, an incidence of 0 percent was expected as transmission with the allograft is unlikely in the situation of a CMV seronegative allograft donor-recipient combination. However, we used CMV unscreened bufly-coat depleted blood during open heart surgery. Apparently, the use of bufly-coat depleted blood did not completely prevent CMV disease in all patients, not even when passive immunization was given.

In conclusion, our study suggests that passive im­munization with anti-CMV immunoglobulin prevents CMV disease but not infection in CMV seronegative heart transplant recipients from a CMV seropositive donor. One can argue that definite conclusions on the efficacy of such a strategy can only be drawn from a prospective, randomized, double-blind controlled study. However, the data from the present uncon­trolled study in heart transplant recipients and the reports from controlled trials in kidney and bone marrow recipients may make such an approach questionable on ethical grounds in view of the reported high incidence of CMV disease.