title: Low incidence of malignancy among sirolimus/cyclosporine-treated renal transplant recipients.
abstract: 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.
authors.affiliation: The University of Texas Medical School at Houston, Division of Immunology and Organ Transplantation, Houston, TX 77030, USA. Barry.D.Kahan@uth.tmc.edu
authors.forename: Barry D
authors.initials: BD
authors.lastname: Kahan
authors.forename: Yarkin K
authors.initials: YK
authors.lastname: Yakupoglu
authors.forename: Linda
authors.initials: L
authors.lastname: Schoenberg
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Knight
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Katz
authors.forename: Deijan
authors.initials: D
authors.lastname: Lai
authors.forename: Charles T
authors.initials: CT
authors.lastname: Van Buren
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus