Simultaneous treatment of concurrent rejection and tissue invasive cytomegalovirus disease without detrimental effects upon patient or allograft survival

Posttransplant cytomegalovirus (CMV) infection has been directly and temporally correlated with decreased patient and allograft survival. Because of this association, prior dogma has dictated that immunosuppression be decreased or maintained, but not increased, and thus rejection episodes have not been treated during active CMV infection. Since 1987, we have treated a group of patients who developed concurrent (within 1-3 days) mild to moderate acute rejection and mild to moderate tissue invasive CMV disease (TI-CMV) with antirejection and antiviral therapy simultaneously. 619 patients underwent renal transplantation between 5/7/87 and 12/13/90 [535 kidney (253 living related, 282 cadaver) and 84 kidney-pancreas]. 18 patients presented with concurrent evidence of TI-CMV plus acute kidney or pancreas allograft rejection. Treatment consisted of iv ganciclovir (DHPG, 5mg/kg iv q 12 h, mean = 14.4 days) for TI-CMV and initial oral or iv steroids (followed by ALG or OKT3 in 13 patients) for rejection. At 30 days, all 18 patients with concurrent TI-CMV and rejection were successfully treated for CMV without DHPG toxicity, although 2 allografts were lost due to unrelenting rejection requiring nephrectomy. 4 patients developed recurrent TI-CMV and 1 patient developed recurrent rejection > 30 days after simultaneous therapy, all of which were successfully treated. A total of 4 deaths occurred due to the following causes: pulmonary embolus, cerebrovascular accident, Candida sepsis, and Aspergillus sepsis, the latter subsequent to treatment of recurrent rejection. We analyzed outcome in patients who developed TI-CMV postrejection (> 14 days) or TI-CMV without rejection and who received DHPG, and noted that patient and allograft survival was not statistically different compared to patients who received simultaneous therapy for both disease processes (p > 0.05). Recipients with or without rejection who never developed TI-CMV, however, did exhibit increased patient and allograft survival when compared to those who were treated for TI-CMV alone or simultaneous TI-CMV plus rejection (p < 0.01). Based upon this analysis, we concluded that: 1) simultaneous treatment of concurrent TI-CMV and acute rejection is feasible, and 2) this does not magnify the adverse effects related to TI-CMV alone, and recommended that: 1) antirejection therapy be instituted with simultaneous administration of DHPG in patient with proven rejection and suspected TI-CMV, 2) the diagnostic work-up for CMV and other pathogens should be vigorously pursued in this setting, and 3) if evidence of progression of CMV disease occurs (despite absence of this event in this series) that antirejection therapy be withdrawn.