Low incidence of malignancy among sirolimus/cyclosporine-treated renal transplant recipients.
BACKGROUND
Malignancies, a well-known complication of immunosuppressive therapy in renal transplant recipients, represent an important cause of long-term morbidity and mortality. One approach to addressing this problem is identifying agents that display antineoplastic properties concomitant with their immunosuppressive effects.


METHODS
We examined the neoplasms among 1008 renal transplant recipients treated at a single center with sirolimus-cyclosporine +/- prednisone.


RESULTS
Clinical and laboratory data, including 62.3+/-26.1 months follow-up (range 27.1-131), revealed 36 tumors in 35 patients (3.6%) presenting at 32.5+/-29.8 months. The 2.4% incidence of skin tumors, the most common neoplasms, was 1.58-fold greater than the general U.S. population. In addition to a 0.4% incidence of posttransplant lymphoproliferative disorders (PTLD) and a 0.2% incidence of renal cell carcinomas, we observed single cases of breast, bladder, endometrial, lung, and brain neoplasms as well as leukemia. The mean trough drug concentrations at the time of diagnosis in affected recipients were within our putative target ranges. In addition to eleven graft losses due to death with a functioning kidney, two were related to chronic rejection following reduced immunosuppression, and one, therapeutic nephrectomy for PTLD. Five of twelve deaths were caused by malignancies; four others among 1008 patients over the entire follow-up were attributed to cardiovascular events; one, to respiratory failure; and two, at distant locations to unknown causes.


CONCLUSIONS
The sirolimus-cyclosporine +/- prednisone combination appears likely to be associated with a reduced incidence of tumors.
Kahan
Barry D
BD
The University of Texas Medical School at Houston, Division of Immunology and Organ Transplantation, Houston, TX 77030, USA. Barry.D.Kahan@uth.tmc.edu
Yakupoglu
Yarkin K
YK
Schoenberg
Linda
L
Knight
Richard J
RJ
Katz
Stephen M
SM
Lai
Deijan
D
Van Buren
Charles T
CT
D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus