Cryptococcosis in liver and kidney transplant recipients receiving anti‐thymocyte globulin or alemtuzumab

Abstract

Rabbit anti-thymocyte globulin (ATG) and alemtuzumab have been used for induction or preconditioning and for the treatment of acute rejection in organ transplant recipients in many centers. Such regimens may lead to a substantial decline in the CD4 lymphocyte count to levels seen in other population groups at high risk of cryptococcosis. In view of this, we examined the impact of such therapy on the cumulative incidence of cryptococcosis among liver and kidney recipients. A total of 834 liver and 727 kidney transplants were performed during the study period. Seven hundred and eighty-one patients did not receive ATG or alemtuzumab; 646 received 1 dose of either drug, and 134 patients received 2 doses of either drug. The cumulative incidence of cryptococcosis was 0.26% (2/781) among those who did not receive ATG or alemtuzumab; 0.3% (2/646) among those who received only 1 dose, and 2.24% (3/134) among those who received 2 doses (P=0.03). There were 5 cases of cryptococcosis in liver recipients and 2 in kidney recipients. There were 3 cases of cryptococcal meningitis, 3 of pneumonia, and 1 of disseminated disease. The 2 kidney recipients had meningitis. Diagnosis occurred at a median of 255 days (range 7-517) after transplantation. The mortality rate was 14.2%. We conclude that the use of 1 dose of ATG or alemtuzumab is not associated with an increased cumulative incidence of cryptococcosis, but that those patients receiving 2 doses are at increased risk.

Fungal infections after lung transplantation

“…Cryptococcosis occurs in a mean of 2.8% of SOT recipients and it has been associated with several novel immunosuppressors [34]. The limited epidemiologic information suggests that the majority of cases in SOT are caused by C. neoformans var.…”

“…Additionally, some studies [15,16] have shown a direct relation between the use of some immunosuppressive drugs and invasive mycoses. Recently, risk factors from fungal infection during the first year after primary paediatric lung transplantation have been analysed.…”

Approach to the immunocompromised patient with pulmonary nodules

“…We identifi ed an increase in opportunistic infection with Aspergillus, Zygomyctes, Nocardia, Cryptococcus, and CMV that was likely related to a combination of the use of antithymocyte globulin (Thymoglobulin; Genzyme Corp., Cambridge, MA) for induction immunosuppression and higher doses of corticosteroids in heart transplant recipients [24]. Others have noted an increased risk of cryptococcosis in liver and kidney transplant recipients who received two doses of antithymocyte globulin (2.24%) versus one dose (0.3%; P = 0.03) [25]. Higher doses of corticosteroids have also been linked to the development of more symptomatic disease in SOT recipients who develop pulmonary cryptococcosis [26].…”

Fungal infections in lung transplant recipients

“…1). Recently, an increase in the cumulative incidence of cryptococcosis among kidney and liver transplant recipients was associated with the use of two doses of antilymphocyte globulin or alemtuzumab [18]. This has not been documented for LTx recipients.…”