BACKGROUND Long-term immunosuppression imposes increased malignancy risk in renal allograft recipients, significantly contributing to overall morbidity and mortality. This study examined malignancy rates in renal allograft recipients at 2 years after conversion to a sirolimus (SRL)-based, calcineurin inhibitor (CNI)-free regimen. METHODS This open-label, randomized, multicenter study (the CONVERT Trial) randomly assigned 830 patients to SRL conversion (n=555) or CNI continuation (n=275). Patients with history of posttransplant lymphoproliferative disease or known/suspected malignancy within 5 years before screening were excluded. As part of standard safety measurements, subjects were monitored for any malignancy occurrence; both skin and nonskin malignancies were reported, even if the patient discontinued from the therapy. Malignancy rates were analyzed based on exposure time to study drugs (i.e., number of events per 100 person-years of follow-up). RESULTS At 2 years postconversion, the total number of malignancies per 100 person-years of exposure was significantly lower among SRL conversion patients compared with CNI continuation (2.1 vs. 6.0, P<0.001). Patients undergoing SRL-based, CNI-free therapy had significantly lower rates of the subset of nonmelanoma skin carcinomas through 2 years postconversion (1.2 vs. 4.3, P<0.001). This difference persisted after excluding patients with a history of malignancy before randomization. The rate of all other malignancies was not significantly different between treatment groups (P=0.058). CONCLUSION In renal allograft recipients, SRL-based immunosuppression was associated with a lower rate of malignancy at 2 years postconversion compared with continuation of CNI-based immunosuppression. This reduction was driven by a significant reduction in nonmelanoma skin carcinoma rates; the rate of all other malignancies was numerically lower but did not achieve statistical significance.

Lower malignancy rates in renal allograft recipients converted to sirolimus-based, calcineurin inhibitor-free immunotherapy: 24-month results from the CONVERT trial.

Post-transplant lymphoproliferative disorders (PTLDs) are serious, life-threatening complications of solid-organ transplantation (SOT) and bone marrow transplantation leading to a high mortality (30-60%). PTLD represents a heterogeneous group of lymphoproliferative diseases. They become clinically relevant because of the expansion of transplantation medicine together with the development of potent immunosuppressive drugs. Although the diagnostic morphological criteria of different forms of PTLD are commonly known, rapid and correct diagnosis is not always easy. Because of the limited number of clinical trials, a consensus is lacking on the optimal treatment of PTLD. This review focuses on incidence, risk factors, clinical picture of the disease and diagnostic tools including histopathology relating to the new classification introduced in 2008 by the World Health Organisation (WHO) and treatment of PTLD.

Post-transplant lymphoproliferative disorder in view of the new WHO classification: a more rational approach to a protean disease?

With improving survival following solid organ transplantation, clinicians must be aware of post-transplant complications. One increasingly frequent complication is the development of malignancy after transplantation. The most common malignancies encountered in the post–solid organ transplant setting are nonmelanoma skin cancers, post-transplant lymphoproliferative disorders,andKaposi’ssarcoma(KS).Thepathogenesisof these tumors is likely related to the immunosuppressive drugs used post-transplantation and subsequent viral infection.Treatmentinvolvesmodificationoftheimmunosuppressive drug regimen, resection of localized disease, and chemotherapy. We present the second reportedcaseofapatientwithlungtransplantationwho developed KS in the lung graft. The Oncologist 2008;13: 769–778

https://theoncologist.onlinelibrary.wiley.com/doi/pdf/10.1634/theoncologist.2007-0251

Malignancy After Solid Organ Transplantation: An Overview

Immunosuppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer (NMSC) and malignancies, including posttransplant lymphoproliferative disorder (PTLD) and solid organ cancer This study sought to investigate the incidence of malignancies and the clinical characteristics and risk factors of the renal transplant patients with solid organ tumors and NMSC We included 1017 patients who received a kidney transplant in our hospital from 1979 to 2007 Results were contrasted with a cohort of patients from the same center without malignancies The mean follow-up of patients in our series was 10 years The mean age at presentation of the malignancy was 61 +/- 5 years The malignancy and NMSC incidences were 6% and 5%, respectively Patients with malignancy had a longer posttransplant time and greater recipient and donor age In the multivariate analysis, independent risk factors for developing NMSC were: male sex (hazard ratio [HR] 31, P = 004); greater patient age (HR 109, P < 001), longer posttransplant time (HR 12, P = 004) and tacrolimus treatment (HR 44, P = 001) Risk factors associated with developing any malignancy were: patient age (HR 106, P < 001), number of grafts (HR 32, P = 019), tacrolimus treatment (HR 25, P = 035), and time posttransplantation (HR 12, P = 011) The mean times to development of an NMSC, solid organ malignancy, on PTLD were 75, 61, or 39 years, respectively The mean survival time from the diagnosis of any malignancy was 96 months (95% confidence interval, 012-30) for solid organ malignancies and 1 month (95% confidence interval, 024-187) for PTLD

Cancer Incidence and Survival in Kidney Transplant Patients

Risk of colorectal carcinoma in post-liver transplant patients: a systematic review and meta-analysis.

De novo malignancies after transplantation are a growing problem of solid organ transplant recipients, due to longer survival follow-up under chronic immunosuppression. The aim of this study was to analyze a population of 582 consecutive kidney (n = 382) and liver (n = 202) transplant recipients, who survived at least 12 months after transplantation, at a single transplant center for the development of de novo cancers. The incidence of de novo malignancies was 7% after both renal and liver transplantation. The median elapsed time from transplant to the diagnosis of de novo malignancy was 45 months (range 3 to 220) months for kidney and 37 months (range 12 to 101 months) for liver transplants. Skin cancers were the most common within renal recipients, while gastroenteric cancers were more frequently encountered in liver transplants. Oropharyngeal and upper digestive tract tumors were always associated with a history of chronic alcohol consumption in liver recipients. Liver transplant recipients treated for acute rejection had a worse cancer prognosis than patients without rejection 1- and 2-year survivals 83% and 63% versus 36% and 17% (P = .026). The estimated 1- and 2-year survival rates for all types of de novo malignancies were 79% and 66%, including 64% and 51% for solid organ tumors versus 89% and 89% for skin cancers and posttransplant lymphoproliferative disorder (PTLD) (P = .17) in renal transplants and 70% and 42%, including 57% and 28% for solid organ tumors versus 85% and 64% for skin cancers and PTLD (P = .43) in liver transplants respectively.

De novo malignancies after kidney and liver transplantations: experience on 582 consecutive cases.

Tracheobronchomegaly, also called Mounier-Kuhn syndrome, consists in dilatation of the trachea and major bronchi because of atrophy or absence of their elastic fibers and smooth muscle cells. Standard chest radiography often does not permit diagnosis because only lateral imaging, obtained with X-rays or chest CT scan, shows the true degree of tracheal dilatation. Surgery has no role in tracheomegaly, except for the complications of tracheal stenosis or pneumothorax. The present work reports cadaveric renal transplantation in a 43-year-old woman affected by end-stage renal disease and suffering from congenital tracheobronchomegaly diagnosed during the first decade of life. No surgical or anesthetic problems were encountered during the immediate perioperative period. The patient did not require pulmonary physiotherapy. Antibiotic prophylaxis was given for 10 days. No pulmonary infection developed, and the patient was discharged from the hospital asymptomatic with normal renal function at 25 days after the transplant. Four months later, the patient experienced bronchitis with cough and fever. Antibiotic therapy was performed with totally resolution of symptoms. At 8 months of follow-up after kidney transplantation, the patient is asymptomatic with normal renal function.

Renal Transplantation in a Patient Affected by Mounier-Kuhn Syndrome

Objective: Urinary infections developing after kidney transplantation may depend on the type of ureterovesical anastomosis performed. Patients and Methods: A randomized prospective study was performed on 56 patients, from October 2004 to March 2006, receiving kidney transplants from cadaveric donors to compare 2 types of ureterovesical anastomosis. We considered the number and types of urinary infections, the duration of their treatment, and their complete/ partial resolution during the first year after transplantation. Twenty-eight patients (group A) underwent ureterovesical anastomosis according to the Lich-Gregoir technique, the other 28 patients (group B) using the Knechtle method. The 2 groups were comparable in terms of donor and recipient characteristics. Results: The mean duration of the period of antibiotic treatment was 17 ± 11 days in group A and 15 ± 7 days in group B (p = 0.63), while the intravenous antibiotic treatment lasted a mean 11 ± 6 days in group A and 10 ± 3 days in group B (p = 0.54). The antibiotic treatment completely resolved the urinary infection in all cases treated. No grafts were lost due to complications of urinary infections. Conclusion: Our data revealed no statistically significant differences between the 2 types of ureterovesical anastomosis considered in terms of the prevalence of infections or graft survival during the first year of follow-up.

Ureterovescical anastomosis and urinary infections after kidney transplantation: two techniques comparison

Single-time kidney transplantation and monolateral nephrectomy for hypertension and antihypertensive therapy in renal transplant recipients.

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De novo malignancies after kidney and liver transplantations: experience on 582 consecutive cases.

Renal Transplantation in a Patient Affected by Mounier-Kuhn Syndrome

Ureterovescical anastomosis and urinary infections after kidney transplantation: two techniques comparison

Single-time kidney transplantation and monolateral nephrectomy for hypertension and antihypertensive therapy in renal transplant recipients.