tacrolimus and Sarcoma--Kaposi

Patient survival time following renal and other solid organ transplantation has been increasing recently, in part due to modern immunosuppressive regimens. However, the probability of malignant tumor formation is also increasing proportionally to survival time, as a side effect of long-term immunosuppression. The primary factor of increased tumor risk is the deficient antitumoral and antiviral function of the immune system. The frequency of posttransplantation tumors is 2 to 4-fold compared to the non-transplanted population, and the distribution of tumor types is also different. The most frequent tumor types--skin cancer, lymphoma, Kaposi's sarcoma, oral cancer, anogenital tumors, etc.--are often associated with oncogenic viruses. Treatment options and the prognosis of posttransplant tumors are worse than in the normal population. The increasing frequency of posttransplantation tumors is an important factor determining the long-term fate of transplant patients. The reduction of carcinogenic agents, the early diagnosis and treatment of tumors and precancerous conditions, low dose immunosuppression and the usage of immunosuppressive agents with an oncologically favorable, anti-proliferative effect will help reduce the risk of posttransplant tumor formation.

Topics: Adrenal Cortex Hormones; Azathioprine; Calcineurin Inhibitors; Cyclosporine; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphoproliferative Disorders; Muromonab-CD3; Neoplasms; Prognosis; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare infiltrative vascular tumors. Currently, no standard treatment regimens exist for KHE/TA. The purpose of our study was to evaluate the efficacy and safety of topical application of tacrolimus for superficial KHE/TA. We examined six patients with superficial KHE/TA. All patients were treated with tacrolimus 0.1% ointment twice daily for at least 12 months. The response rate was 100%, including three nearly complete remissions. Only one patient experienced local pruritus during treatment. The data constituted an intriguing rationale for clinical trials of topical tacrolimus in the treatment of superficial KHE/TA.

Topics: Administration, Cutaneous; Biopsy; Child, Preschool; Female; Hemangioendothelioma; Hemangioma; Humans; Infant; Kasabach-Merritt Syndrome; Male; Off-Label Use; Ointments; Photography; Pruritus; Sarcoma, Kaposi; Skin; Skin Neoplasms; Tacrolimus; Treatment Outcome

We report a patient with kaposiform haemangioendothelioma successfully treated with topical tacrolimus and compression bandaging.

Topics: Hemangioendothelioma; Humans; Kasabach-Merritt Syndrome; Sarcoma, Kaposi; Tacrolimus

Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are associated with an increased cancer risk. However, whether mammalian target of rapamycin inhibitors (mTORis), including sirolimus and everolimus, decrease the cancer risk in patients receiving CNIs remains uncertain. We aimed to determine whether mTORis are associated with a decreased cancer risk in patients receiving CNIs using data mining of a spontaneous adverse reaction database.. Disproportionality analysis was conducted using the U.S. Food and Drug Administration Adverse Event Reporting System database (2004 - 2019) with reporting odds ratio and information component being used to indicate a signal.. Data subset analyses indicated that sirolimus and everolimus were not associated with a decreased cancer risk in patients receiving cyclosporine or tacrolimus but were associated with an increased risk of nonmelanoma skin cancer (NMSC) and Kaposi's sarcoma.. mTORis are not associated with a decreased cancer risk but are associated with a further increase in the risk of NMSC and Kaposi's sarcoma in patients receiving CNIs. Further studies are necessary to clarify the mechanism underlying the association between mTORis and NMSC or Kaposi's sarcoma.

Topics: Calcineurin Inhibitors; Cyclosporine; Data Mining; Everolimus; Humans; Immunosuppressive Agents; Sarcoma, Kaposi; Sirolimus; Tacrolimus; TOR Serine-Threonine Kinases

Kaposi sarcoma (KS) is the most common tumor in patients with human immunodeficiency virus (HIV), and its frequency is increasing after organ transplantation in HIV-negative patients. A 28-year-old woman had preemptive kidney transplantation from her 48-year-old mother. In the postoperative ninth month, an exophytic mass was found in the upper medial conjunctiva of the right eye. The lesion was excised under local anesthesia, and cryotherapy was applied to the surgical area. The biopsy result was reported as KS. Treatment with tacrolimus was switched to everolimus (EVO), but EVO was discontinued because of pneumonitis. The patient was followed without any recurrences after the excision of the conjunctival lesion. No local or systemic recurrence was observed in the 14th month after surgical excision and local cryotherapy. Local treatment and the reduction of immunosuppressive therapy may be effective in the treatment of conjunctival KS.

Topics: Adult; Conjunctival Neoplasms; Everolimus; Female; HIV Infections; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Sarcoma, Kaposi; Tacrolimus

Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors, chemotherapy, or a combination of these.. To obtain an overview of clinical strategies about the current treatment of KS.. We conducted a multicenter retrospective cohort study including 145 solid organ transplant recipients diagnosed with KS between 1985 and 2011 to collect data regarding first-line treatment and response at 6 months.. Overall, 95%, 28%, and 16% of patients had reduction of immunosuppression, conversion to mTOR inhibitor, and chemotherapy, respectively. Patients treated with chemotherapy or mTOR inhibitor conversion were more likely to have visceral KS. At 6 months, 83% of patients had response, including 40% complete responses.. The retrospective design of the study.. Currently available therapeutic options seem to be effective to control KS in most patients. Tapering down the immunosuppressive regimen remains the cornerstone of KS management.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Substitution; Europe; Female; Graft Survival; Humans; Immunosuppressive Agents; Male; Middle Aged; Organ Transplantation; Retrospective Studies; Sarcoma, Kaposi; Sirolimus; Skin Neoplasms; Survival Rate; Tacrolimus; TOR Serine-Threonine Kinases

Topics: Antibodies, Viral; Drug Substitution; Erythema; Everolimus; Herpesviridae Infections; Herpesvirus 8, Human; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Sarcoma, Kaposi; Tacrolimus; Thoracic Neoplasms; Tissue Donors; Viremia

Topics: Adult; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Male; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus

Organ transplant recipients have a high incidence of cancer associated with persistent viral infections, such as human herpes virus 8. This virus is associated with Kaposi's sarcoma, and a change in the dose or type of immunosuppression regimen should be the first step in its treatment. A multidisciplinary approach with nephrologists, dermatologists and oncologists is necessary for the management of this disease. We report a clinical case with atypical presentation and discuss the treatment options.

Topics: Female; Herpesvirus 8, Human; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Sarcoma, Kaposi; Tacrolimus

We present a case report of a patient with diffuse skin and systemic Kaposi's sarcoma (KS), 1 year after renal transplantation. A concomitant Pyrenochaeta romeroi granuloma of the right hallux was diagnosed and illustrated an important immunodysfunction in our patient. Four months after reduction in immunosuppression and switch to everolimus, a total regression of the KS was observed. Reduction in the immunosuppression and treatment with terbinafine cleared the P. romeroi infection, while lowering immunosuppression and changing the type of immunosuppressive therapy were important steps in the successful management of the KS. In recent years, evidence of the antitumor effects of everolimus is increasing: total regression of KS in combination with renal function preservation in renal graft recipients is possible with mammalian target of rapamycin (mTOR) inhibitor-based regimens. In addition, with increasing numbers of human immunodeficiency virus-positive transplant recipients, mTOR inhibitors may play a more crucial role in the management of KS.

Topics: Adult; Dermatomycoses; Drug Substitution; Everolimus; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Neoplasms; Mycophenolic Acid; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus; Treatment Outcome

Topics: Delayed Diagnosis; Herpesvirus 8, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus; Thorax

With this study we aimed to research the effects of immunosuppressive drugs, their cumulative doses, and viral infections on development of malign tumors in patients who have undergone treatment for 5 years.. We examined 100 patients who underwent renal transplantation from 2004 to 2009. Patients had mycophenolate mofetil and steroid in addition to cyclosporine, sirolimus, or tacrolimus as immunosuppressive treatment. For malignancy screening, physical examination, radiologic and endoscopic screening were done, and immunosuppressive drugs and their cumulative doses, age, sex, body mass index (BMI), dialysis history, and viral infection history were investigated.. The mean age of patients was 42.03 ± 11.30 years. There were 1 colon cancer patient, 1 retroperitoneal liposarcoma, 1 renal oncocytoma, 3 Kaposi sarcoma patients treated with cyclosporine; in those treated with Tac there were 1 basal cell carcinoma, 1 Kaposi sarcoma, 2 thyroid carcinoma, 1 breast carcinoma, 1 bladder carcinoma, 1 renal cell carcinoma, and 1 colon carcinoma patients. The mean age of patients having carcinoma was statistically significant compared with those without cancer (P < .01). The prednisolone cumulative dose was significantly higher in carcinoma patients than in patients without carcinoma (P < .01).. The use of long-term chronic immunosuppressive therapy may increase the development of cancer. The risk of carcinoma increases with increasing drug dose and time period of the immunosuppressive drug. There was not a negative effect on cancer prevalence in patients with cyclosporine or tacrolimus. But the cumulative dose of steroids significantly increased malignancy occurence.

Topics: Adult; Breast Neoplasms; Carcinoma; Colonic Neoplasms; Cyclosporine; Early Detection of Cancer; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Neoplasms; Retroperitoneal Neoplasms; Sarcoma, Kaposi; Sirolimus; Steroids; Tacrolimus; Thyroid Neoplasms; Time Factors; Urologic Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Delayed Diagnosis; Dermatitis; Diagnostic Errors; Drug Substitution; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Postoperative Complications; Postoperative Period; Prednisone; Sarcoma, Kaposi; Sirolimus; Skin Neoplasms; Tacrolimus; Vinblastine

Kaposi's sarcoma (KS) is a vascular lesion of low-grade malignant potential caused by the complex interactions between geographic, genetic, environmental, and immunological factors. We recently experienced a rare case of KS associated with rheumatoid arthritis in a patient receiving corticosteroids and tacrolimus; the KS demonstrated unusually aggressive clinical behavior. We herein report the details of the clinical course and discuss the possible contribution of corticosteroids and tacrolimus to the development of aggressive KS in the present case.

Topics: Adrenal Cortex Hormones; Aged; Arthritis, Rheumatoid; Bone Neoplasms; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Male; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus

A patient with human immunodeficiency virus infection and end-stage renal disease received a renal transplant. At the time of surgery, the patient was on quadruple antiretroviral therapy (lamivudine, zidovudine, and amprenavir/ritonavir). Immunosuppression was initiated with basiliximab, corticosteroid, mycophenolate mofetil, and a single 0.5 mg dose of tacrolimus. In the following days, an increase in tacrolimus concentration was observed with a peak of 37 ng/mL. Tacrolimus half-life was 6.5 days and tacrolimus maintenance dose was 0.5 mg every 4 days. Eleven months later, the patient had developed Kaposi sarcoma. Tacrolimus was replaced by sirolimus (first dose 1 mg), and the patient was stabilized with 1.5 mg of sirolimus once a week. Increased tacrolimus half-life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P-glycoprotein inhibition by protease inhibitors. Close monitoring is required in the management of tacrolimus and sirolimus dosing regimens when combined with ritonavir boosted HIV-1 protease inhibitors.

Topics: Drug Interactions; Half-Life; HIV Infections; HIV Protease Inhibitors; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Sarcoma, Kaposi; Sirolimus; Tacrolimus

SRL is a new and potent immunosuppressive agent that has been successfully introduced in organ transplantation. In contrast to other immunosuppressive agents, SRL has a potent antitumor activity both in vitro and in vivo. Herein, we report a child with Kaposi's sarcoma that was diagnosed 30 months after LDLT and treated successfully with only conversion to SRL monotherapy. KS regressed completely at the end of the first month and remained in remission during 28 months follow-up.

Topics: Antibiotics, Antineoplastic; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Infant; Liver Transplantation; Living Donors; Sarcoma, Kaposi; Sirolimus; Tacrolimus; Treatment Outcome

Topics: Angiogenesis Inhibitors; Cyclosporine; Humans; Immunosuppressive Agents; Neoplasms; Organ Transplantation; Sarcoma, Kaposi; Sirolimus; Tacrolimus; United States

Kaposi's sarcoma is a relatively rare but potentially fatal malignancy which affects immunosuppressed individuals. It has been found to occur especially in association with cyclosporine and tacrolimus use and with concurrent cytomegalovirus infection. When detected and treated early, it usually carries a good prognosis and responds well to measures increasing immunocompetence. We report a case of cutneous Kaposi's sarcoma occurring in a cardiac transplant patient treated with tacrolimus.

Topics: Biopsy; Diagnosis, Differential; Female; Follow-Up Studies; Graft Rejection; Heart Failure; Heart Transplantation; Humans; Immunosuppressive Agents; Middle Aged; Risk Factors; Sarcoma, Kaposi; Tacrolimus; Tomography, X-Ray Computed

Topics: Acquired Immunodeficiency Syndrome; Administration, Topical; Adult; Dermatitis, Seborrheic; Humans; Immunosuppressive Agents; Male; Psoriasis; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus

Topics: Acquired Immunodeficiency Syndrome; Administration, Topical; Adult; Humans; Immunosuppressive Agents; Male; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus

Topics: Adult; Biopsy; Female; Gastric Mucosa; Herpesvirus 8, Human; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymph Nodes; Mycophenolic Acid; Postoperative Complications; Sarcoma, Kaposi; Tacrolimus

Topics: Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Leg; Middle Aged; Postoperative Complications; Retreatment; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus

Topics: Adult; Antineoplastic Agents; Cyclosporine; Doxorubicin; Drug Carriers; Humans; Immunosuppressive Agents; Kidney Transplantation; Liposomes; Male; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus

Topics: Herpesvirus 8, Human; Humans; Immunosuppressive Agents; Liver Transplantation; Postoperative Complications; Sarcoma, Kaposi; Saudi Arabia; Tacrolimus

We report two cases of Kaposi's sarcoma (KS) after orthotopic liver transplantation for cirrhosis of the liver related to hepatitis C virus. Both cases were Saudi-born Arabs who were negative for human immunodeficiency virus; one patient was receiving FK506 plus prednisolone, and the other patient was receiving FK506. One patient died of fulminant multicentric KS. The other patient, with lesions confined to the lower limbs, is still alive. These are the first case reports of KS in liver transplant recipients in the Kingdom of Saudi Arabia and, to our knowledge, these are the first case reports of KS in liver transplant recipients on FK506. All previous reports were related to either cyclosporine or conventional immunosuppressive therapy, i.e., azathioprine plus prednisolone.

Topics: Aged; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Prevalence; Sarcoma, Kaposi; Saudi Arabia; Tacrolimus