Anthracycline chemotherapy for Kaposi's sarcoma in renal transplant recipients: a case series

Kaposi's sarcoma in recipients of renal transplants

Kaposi's sarcoma (KS) can be a complication of solid organ transplantation, but with an important incidence rate variability in different geographical areas. Here we analyzed the incidence rate, timing and clinical correlates of KS, in a cohort of Italian solid organ transplant recipients from four distinct transplantation centers. A total of 1721 renal, heart and liver transplant recipients were recruited between 1997 and 2004. KS was diagnosed in 40 patients, after a median follow up of 1 year (range 0.8-5.1). Visceral involvement was detected in 7/40 patients. Incidence rate of KS in the whole population was 2.3 cases per 1000 individuals per year. The standardized incidence rate (SIR) for KS in renal transplant recipients was 149.9 (95% CI 103.0-212.0), with the excess risk greater among women (SIR 316.0) than among men (SIR 133.6). In a Cox proportional hazard regression model, age at transplantation equal or older than 30 years and only combined immunosuppressive therapy with mycophenolate mofetil + cyclosporine + prednisolone were independently associated with KS. Italian organ transplant recipients have an increased risk (about 100 times greater) for KS compared to the general population, especially during the first two years after transplantation. Age older than 30 years at transplantation and a more aggressive immunosuppressive regimen were both independent risk factors for the disease.

Prevalence, Incidence and Correlates of HHV-8/KSHV Infection and Kaposi's Sarcoma in Renal and Liver Transplant Recipients

Kidney Transplantation in Patients With HIV Infection

Skin cancers are the most common malignant occurrences in transplant recipients (1–3). It is widely recognized that immunosuppressive treatments increase the risk of skin cancer in transplant recipients (4, 5). A decrease of tumors after reduction or cessation of these drugs has been reported in aggressive disease that may lead to graft loss (6). However, some experimental studies have showed that sirolimus (SRL) slows and inhibits the growth of established experimental tumors (7) while simultaneously protecting the allograft from immunological damage (8). Clinical data has showed a lower incidence of new malignancies, after renal transplantation, in recipients under immunosuppression with a mammalian target of rapamycin inhibitor (9, 10). We report 24 renal transplant recipients with multiple skin cancers who subsequently had their immunosuppression protocol changed to SRL. The aims were to evaluate the frequency of skin cancer and renal function pre- and postintroduction of SRL. It was reviewed the patient's charts. One patient was excluded because he used SRL for less than three months and died. The creatinine clearance was calculated by the Cockcroft-Gault formula. At the time the skin cancer was diagnosed, 69.5% of the patients were using cyclosporin (CsA)+azathioprine (Aza)+prednisone (Pred), 13% Aza+Pred, 8.7% tacrolimus+ Aza+Pred, and 8.7% CsA+mofetil mycophenolate+Pred. The immunosuppression regimen consisted of an initial dose of SRL of 2 mg/day with rapid withdrawal of cyclosporine or tacrolimus and azathioprine or mofetil mycophenolate. The blood SRL level aimed was 4–10 μg/L. Prednisone was maintained at 5–10 mg/day. Statistical analysis was performed using the SPSS package. The means pre- and postconversion were analyzed by paired t test (significant P value <0.05) with a confidence interval (CI) of 95%. Of the 23 patients involved in the study, 22 were white, 15 were male, 13 received the graft from a living donor, 20 were primary transplants. The mean age was 54.3 years (SD: 12.6). The histology type of the skin cancer presented were squamous cell carcinomas (SCC; n=11), basal cell carcinomas (BCC) and SCC (n=8), melanoma (n=2), Kaposi's sarcoma (n=1) and SCC and renal cell carcinoma (n=1). The average follow-up time from transplant surgery to diagnosis of the first skin cancer was 86 months (CI: 61.5–110.8) and for the second SCC or BCC was 13.8 months (CI: 4.8–22.8). The mean follow-up time after the introduction of SRL was 22.4 months (CI: 16–28.8). Before the introduction of SRL each patient had an average of 3.2 (CI: 2.2–4.2) skin cancer episodes and after 0.7 (CI: 0.1–1.3) episodes (P<0.001). Sixteen patients had no new episodes of skin cancer. There was no acute rejection episode during the follow up. The mean creatinine clearance pre-SRL was 53 ml/min (CI: 42.4–63.6), three months post-SRL was 54.2 (CI: 43.3–65.2), six months 54.3 (CI: 42.3–63.3), one year 54.8 (CI: 40.4–69.1), and two years 55.8 (CI: 31.6–80.1). During the follow-up, two patients died (one with metastatic melanoma 11 months after conversion and another with Kaposi's sarcoma). Due to the short follow up time after conversion to SRL, it is difficult to be sure that this conversion reduces the incidence of the skin cancer. There is only one other paper published, which has evaluated the effects of the introduction of SRL in renal transplant recipients with cancer. This study showed that SRL inhibited the progression of dermal Kaposi's sarcoma while providing effective immunosuppression (11). Other clinical data reported a lower rate of skin cancer in patients treated with SRL (8, 12). An analysis in the Organ Procurement and Transplantation Network database showed a lower incidence of any new posttransplant malignancies in renal recipients with SRL/everolimus alone and SRL/everolimus plus CsA/Tac compared to CsA/Tac (0.6%, 0.6%, and 1.8%, respectively; P<0.001) even in a short-term follow-up (censored at 963 days after transplantation) (9). A multicenter trial with 430 renal transplant recipients were randomly assigned to remain on CsA+ SRL+steroids or to have CsA withdrawn three months after transplantation. A lower relative risk was demonstrated at five years, and a delay of the appearance of the first skin cancer in the group after CsA withdrawal (491 versus 1126 days; P=0.007) (10). Regarding the follow-up time, our mean time for the second skin cancer before conversion was 13.8 months and the mean follow up after conversion was 22.4 months, which could constitute a long enough exposure time for the development of new lesions. In renal transplant patients with SCC the average time for the appearance of a second tumor was 20.03 months (13). Based on the literature data and the results of this study, we plan a multicenter randomized trial of conversion to SRL in patients presenting the first episode of skin cancer. Our data suggests that in renal transplants recipients with skin cancer, conversion to SRL may reduce the incidence of new lesions, while renal function remains stable. Chiara Scaglioni Tessmer Luiza Vieira da Silva Magalhães Faculdade de Medicina Universidade Federal de Pelotas Porto Alegre, Brazil Elizete Keitel Cristiana Valar Diego Gnatta Ronivan Luis Dal Pra Fabiano Roldão Silveira Auri Ferreira dos Santos João Carlos Goldani Valter Duro Garcia Nephrology Department, Renal and Pancreas Transplant Unit Complexo Hospitalar Santa Casa Porto Alegre, Brazil Clotilde Druck Garcia Fundação Faculdade Federal de Ciências Médicas de Porto Alegre Porto Alegre, Brazil

Urinary Tract Infections in Solid Organ Transplant Recipients

Introduction: Cytomegalovirus (CMV) glycoprotein B (gB), encoded by gpUL55, is crucial for CMV's cellular entry and a potential pathogenicity marker. We investigated CMV gB genotype distribution in renal and haematopoietic stem cell transplant (HSCT) recipients, assessing correlations with disease. Materials and methods: 264 clinical samples from 110 renal and 154 HSCT recipients at a tertiary hospital in Kuala Lumpur, Malaysia were analysed. Quantitative PCR detected four CMV gB genotypes (gB1-4), and clinical data correlations were assessed. CMV serostatus of donors (D) and recipients (R) was determined pre-transplantation. Results: In renal transplant recipients, 48.2% exhibited single-genotype CMV, with gB2 (20.9%) and gB1 (17.3%) most prevalent. HSCT recipients showed 47.3% single-genotype CMV, primarily gB2 (20.7%) and gB1 (17.0%). Mixed-genotype infections were observed in 51.8% of renal transplant and 52.7% of HSCT recipients, particularly gB1-gB2 (65.8%). Mixed gB genotypes showed no significant CMV disease association in renal transplant recipients (p = 0.307) and HSCT recipients (p = 0.176). Virus load comparisons indicated significant differences in both groups, but renal transplant recipients with mixed infections had a higher median viral load. The majority of both recipient groups were D+/R+ (84.5% renal, 79.2% HSCT). Primary diagnoses among recipients varied, including glomerulonephritis, diabetes mellitus, hypertension, acute leukemias, lymphomas, and other conditions. Conclusion: This study reveals the diversity of CMV genotypes in renal and HSCT transplant recipients and their potential impact on disease correlation, providing insights into genotype prevalence, viral load association, and CMV disease risk.

The incidence of Kaposi's sarcoma (KS) is greatly increased in renal transplant recipients compared with the general population, with particular prevalence in certain ethnic groups where it can occur in up to 5% of transplant recipients. The increased incidence of disease in transplant populations may, in part, be attributed to the choice of immunosuppressive regimen, with calcineurin inhibitor (CNI)-based immunosuppression being associated with the development of the tumour. A number of small studies have recently demonstrated that conversion to proliferation signal inhibitors (PSIs) along with the concomitant withdrawal of CNIs leads to a rapid resolution of both cutaneous and visceral Kaposi's lesions. In agreement with these data the abrupt onset of KS has been observed following the withdrawal of PSIs. Histological examination of lesions from patients with KS supports data from animal models which suggests that PSIs inhibit tumour angiogenesis through impaired vascular endothelium growth factor production, a key element in the development of the tumour. Previously unpublished data on renal transplant recipients from a number of European and Australian centres have been pooled to provide further insight into the use of PSIs in the management of post-transplant KS. Both members of the PSI class, everolimus and sirolimus, along with CNI withdrawal lead to regression of KS lesions in 11 out of 12 patients. Conversion to PSIs was generally well tolerated with stable renal function maintained in most patients and no episodes of acute rejection recorded. PSIs provide a potential treatment option in the management of post-transplant KS and should be considered for use in renal transplant recipients who develop the disease.

Kaposi's sarcoma: The most common tumor after renal transplantation in Saudi Arabia

This study investigates the association between human herpesvirus eight (HHV8) and Kaposi's sarcoma (KS), the most common cancer occurring in renal transplant recipients in Saudi Arabia. A cross-sectional study of seroreactivity to HHV8 antigens in posttransplant KS patients from a tertiary care hospital in Riyadh, Saudi Arabia, and in control subjects without KS was conducted. Seroreactivity rates were determined using immunoblotting assays to detect antibodies to two lytic cycle HHV8 antigens: p40, an antigen found in infected cells, and sVCA, an HHV8-encoded small viral capsid antigen expressed in Escherichia coli. Antibodies to HHV8 p40 and sVCA were present in a significantly higher proportion of renal transplant patients with KS (13 of 14 patients) compared to renal transplant patients without KS (5 of 18; P<0.001) and compared to other control individuals (6 of 44; P<0.001). HHV8 seroreactivity was more common among patients with renal failure (28%) than among other control groups (7%). The serologic results provide evidence of a strong association between HHV8 and posttransplant KS in Saudi Arabia.

Monitoring Antitumor Efficacy of Rapamycin in Kaposi Sarcoma

Objective:The aim of this study was to present our experience in liver transplantation recipients and renal transplantation recipients during caesarean section.Methods:Retrospective data regarding liver transplantation recipients and renal transplantation recipients who underwent caesarean section between January 1997 and January 2017 have been collected from the hospital records.Results:Fourteen live births occurred from 5 liver transplantation recipients and 9 renal transplantation recipients, all of them from caesarean section. The mean maternal age (28.4 ± 4.0 years vs. 29.2 ± 4.1 years, P = .38), body weight before conception (57.4 ± 8.8 kg vs. 64.5 ± 8.2 kg, P = .48), and the time from transplantation to conception (99.0 ± 50.7 months vs. 101.0 ± 57.5 months, P = .46) were similar for 5 liver transplantation recipients and 9 renal transplantation recipients, respectively. Four caesarean sections were performed under general anaesthesia, whereas spinal anaesthesia was used in 10 patients. The mean birth weight was similar (2502 ± 311g vs. 2161 ± 658 g, P = .3). There were 3 premature deliveries in liver transplantation recipients versus 6 premature deliveries in renal transplantation recipients and 2 low-birth-weight infants (<2500 g) in liver transplantation recipients versus 4 in renal transplantation recipients among 14 newborns. Infants small for gestational age were diagnosed in 9/14 (3 liver transplantation recipients versus 6 renal transplantation recipients, P = 1).Conclusion:General and regional anaesthesia can be safely used during caesarean delivery of liver transplantation recipients and renal transplantation recipients without increased risk of graft losses. Prematurity and low birth weight were mainly due to the cytotoxic drugs for immunosuppression. There are no differences in liver transplantation recipients and renal transplantation recipients for maternal and foetal complications according to our data.

Mucoepidermoid parotid carcinoma after renal transplantation

Incidence and Management of Kaposi Sarcoma in Renal Transplant Recipients: The Greek Experience

We describe a case of Kaposi's sarcoma that developed in a renal transplant recipient as early as 5 months after the transplant. The Kaposi's sarcoma evolved in an aggressive manner, involving the oral mucosa, the cervical and mediastinal lymph nodes, the gastrointestinal tract, and possibly the lung. Histological features of tuberculosis were also detected incidentally on an excisional biopsy of the lymph node. The patient was given 12 months of antituberculous chemotherapy. At the same time, immunosuppression was gradually tapered over a 2- to 3-week period. Despite the aggressive nature of the disease, the Kaposi's sarcoma regressed completely without the institution of chemotherapy. The patient remained disease-free after a follow-up period of 30 months. The kidney allograft, however, was rejected and the patient required dialysis again. Although lymphadenopathy is a well-recognized feature in organ transplant recipients who develop Kaposi's sarcoma, one has to watch out for other coexisting diseases, such as tuberculosis, lymphoma, and cytomegalovirus infection.