FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 352:1317-1323 March 31, 2005 Number 13 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Dantal, J. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Recipients of organ transplants are susceptible to Kaposi's sarcoma as a result of treatment with immunosuppressive drugs. Sirolimus (rapamycin), an immunosuppressive drug, may also have antitumor effects.

Methods We stopped cyclosporine therapy in 15 kidney-transplant recipients who had biopsy-proven Kaposi's sarcoma and began sirolimus therapy. All patients underwent an excisional biopsy of the lesion and one biopsy of normal skin at the time of diagnosis. A second biopsy was performed at the site of a previous Kaposi's sarcoma lesion six months after sirolimus therapy was begun. We examined biopsy specimens for vascular endothelial growth factor (VEGF), Flk-1/KDR protein, and phosphorylated Akt and p70S6 kinase, two enzymes in the signaling pathway targeted by sirolimus.

Results Three months after sirolimus therapy was begun, all cutaneous Kaposi's sarcoma lesions had disappeared in all patients. Remission was confirmed histologically in all patients six months after sirolimus therapy was begun. There were no acute episodes of rejection or changes in kidney-graft function. Levels of Flk-1/KDR and phosphorylated Akt and p70S6 kinase were increased in Kaposi's sarcoma cells. The expression of VEGF was increased in Kaposi's sarcoma cells and even more so in normal skin cells around the Kaposi's sarcoma lesions.

Conclusions Sirolimus inhibits the progression of dermal Kaposi's sarcoma in kidney-transplant recipients while providing effective immunosuppression.

Source Information

From the Division of Nephrology, Department of Emergency and Transplantation (G.S., A.S., B.I., S.D., F.P.S., G.G.), and the Division of Plastic Surgery (G.M.), University of Bari, Bari; and the Division of Nephrology, Departments of Biomedical Sciences (A.L., L.G.) and Clinical Pathology (E.R.), University of Foggia, Foggia (L.G.) — both in Italy.

Address reprint requests to Dr. Grandaliano at the Division of Nephrology, Department of Emergency and Transplantation, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy, or at g.grandaliano{at}nephro.uniba.it.

Full Text of this Article

Related Letters:

Kaposi's Sarcoma after Renal Transplantation
Kanitakis J., Edey M. M., Gutiérrez-Dalmau A., Campistol J. M., Stallone G., Schena A., Grandaliano G.
Extract | Full Text | PDF  
N Engl J Med 2005; 353:846-847, Aug 25, 2005. Correspondence

This article has been cited by other articles:

• Hochegger, K., Jansky, G. L., Soleiman, A., Wolf, A. M., Tagwerker, A., Seger, C., Griesmacher, A., Mayer, G., Rosenkranz, A. R. (2008). Differential Effects of Rapamycin in Anti-GBM Glomerulonephritis. J. Am. Soc. Nephrol. 19: 1520-1529 [Abstract] [Full Text]  
• Zafar, S. Y., Howell, D. N., Gockerman, J. P. (2008). Malignancy After Solid Organ Transplantation: An Overview. The Oncologist 13: 769-778 [Abstract] [Full Text]  
• Walsh, S. B., Summers, S. A., Amlot, P. L., Sheaff, M. T., Neild, G. H. (2008). Rapamycin-induced remission of Kaposi's sarcoma is not associated with expansion of cytotoxic T-lymphocyte subsets. NDT Plus 0: sfn068v1-sfn068 [Abstract] [Full Text]  
• Wang, L., Damania, B. (2008). Kaposi's Sarcoma-Associated Herpesvirus Confers a Survival Advantage to Endothelial Cells. Cancer Res. 68: 4640-4648 [Abstract] [Full Text]  
• Saggar, S., Zeichner, J. A., Brown, T. T., Phelps, R. G., Cohen, S. R. (2008). Kaposi's Sarcoma Resolves After Sirolimus Therapy in a Patient With Pemphigus Vulgaris. Arch Dermatol 144: 654-657 [Abstract] [Full Text]  
• Guenova, E., Metzler, G., Hoetzenecker, W., Berneburg, M., Rocken, M. (2008). Classic Mediterranean Kaposi's Sarcoma Regression With Sirolimus Treatment. Arch Dermatol 144: 692-693 [Full Text]  
• Weikert, B. C., Blumberg, E. A. (2008). Viral Infection after Renal Transplantation: Surveillance and Management. CJASN 3: S76-S86 [Abstract] [Full Text]  
• Cohen, E. E.W. (2008). mTOR: The Mammalian Target of Replication. JCO 26: 348-349 [Full Text]  
• Pascual, J., Galeano, C., Celemin, D., Alarcon, M. C., Marcen, R., Fernandez, A. M., Burgos, F. J., Ortuno, J. (2007). Uneventful Thoracic Healing With Everolimus After Aortic Valve Replacement. Ann. Thorac. Surg. 84: 271-272 [Abstract] [Full Text]  
• Dantal, J., Pohanka, E. (2007). Malignancies in renal transplantation: an unmet medical need. Nephrol Dial Transplant 22: i4-i10 [Abstract] [Full Text]  
• Campistol, J. M., Schena, F. P. (2007). Kaposi's sarcoma in renal transplant recipients--the impact of proliferation signal inhibitors. Nephrol Dial Transplant 22: i17-i22 [Abstract] [Full Text]  
• Campistol, J. M., Albanell, J., Arns, W., Boletis, I., Dantal, J., de Fijter, J. W., Mortensen, S. A., Neumayer, H.-H., Oyen, O., Pascual, J., Pohanka, E., Schena, F. P., Seron, D., Sparacino, V., Chapman, J. R. (2007). Use of proliferation signal inhibitors in the management of post-transplant malignancies--clinical guidance. Nephrol Dial Transplant 22: i36-i41 [Abstract] [Full Text]  
• Gutierrez-Dalmau, A., Campistol, J. M. (2007). The role of proliferation signal inhibitors in post-transplant malignancies. Nephrol Dial Transplant 22: i11-i16 [Abstract] [Full Text]  
• Perry, B., Banyard, J., McLaughlin, E. R., Watnick, R., Sohn, A., Brindley, D. N., Obata, T., Cantley, L. C., Cohen, C., Arbiser, J. L. (2007). AKT1 Overexpression in Endothelial Cells Leads to the Development of Cutaneous Vascular Malformations In Vivo. Arch Dermatol 143: 504-506 [Abstract] [Full Text]  
• Letavernier, E., Bruneval, P., Mandet, C., Van Huyen, J.-P. D., Peraldi, M.-N., Helal, I., Noel, L.-H., Legendre, C. (2007). High Sirolimus Levels May Induce Focal Segmental Glomerulosclerosis De Novo. CJASN 2: 326-333 [Abstract] [Full Text]  
• Tomlanovich, S. J., Vincenti, F. (2007). Sirolimus: Defining Nephrotoxicity in the Renal Transplant Recipient. CJASN 2: 198-199 [Full Text]  
• Sin, S.-H., Roy, D., Wang, L., Staudt, M. R., Fakhari, F. D., Patel, D. D., Henry, D., Harrington, W. J. Jr, Damania, B. A., Dittmer, D. P. (2007). Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling. Blood 109: 2165-2173 [Abstract] [Full Text]  
• SCHUIND, F., ABRAMOWICZ, D., SCHNEEBERGER, S. (2007). Hand Transplantation: The State-of-the-Art. J Hand Surg Eur Vol 32: 2-17 [Abstract] [Full Text]  
• Di Paolo, S., Teutonico, A., Leogrande, D., Capobianco, C., Schena, P. F. (2006). Chronic Inhibition of Mammalian Target of Rapamycin Signaling Downregulates Insulin Receptor Substrates 1 and 2 and AKT Activation: A Crossroad between Cancer and Diabetes?. J. Am. Soc. Nephrol. 17: 2236-2244 [Abstract] [Full Text]  
• Djamali, A., Samaniego, M., Muth, B., Muehrer, R., Hofmann, R. M., Pirsch, J., Howard, A., Mourad, G., Becker, B. N. (2006). Medical Care of Kidney Transplant Recipients after the First Posttransplant Year. CJASN 1: 623-640 [Abstract] [Full Text]  
• Wang, L., Dittmer, D. P., Tomlinson, C. C., Fakhari, F. D., Damania, B. (2006). Immortalization of Primary Endothelial Cells by the K1 Protein of Kaposi's Sarcoma-Associated Herpesvirus.. Cancer Res. 66: 3658-3666 [Abstract] [Full Text]  
• Wahl, P. R., Serra, A. L., Le Hir, M., Molle, K. D., Hall, M. N., Wuthrich, R. P. (2006). Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant 21: 598-604 [Abstract] [Full Text]  
• McAlister, V. C. (2006). Regression of Cutaneous and Gastrointestinal Telangiectasia with Sirolimus and Aspirin in a Patient with Hereditary Hemorrhagic Telangiectasia. ANN INTERN MED 144: 226-227 [Full Text]  
• Campistol, J. M., Eris, J., Oberbauer, R., Friend, P., Hutchison, B., Morales, J. M., Claesson, K., Stallone, G., Russ, G., Rostaing, L., Kreis, H., Burke, J. T., Brault, Y., Scarola, J. A., Neylan, J. F., for the Rapamune Maintenance Regimen Study Group, (2006). Sirolimus Therapy after Early Cyclosporine Withdrawal Reduces the Risk for Cancer in Adult Renal Transplantation. J. Am. Soc. Nephrol. 17: 581-589 [Abstract] [Full Text]  
• Katano, H., Hogaboam, C. M. (2005). Herpesvirus-associated Pulmonary Hypertension?. Am. J. Respir. Crit. Care Med. 172: 1485-1486 [Full Text]  
• Izzedine, H., Brocheriou, I., Frances, C. (2005). Post-Transplantation Proteinuria and Sirolimus.. NEJM 353: 2088-2089 [Full Text]  
• Kanitakis, J., Edey, M. M., Gutierrez-Dalmau, A., Campistol, J. M., Stallone, G., Schena, A., Grandaliano, G. (2005). Kaposi's Sarcoma after Renal Transplantation. NEJM 353: 846-847 [Full Text]  
• (2005). Sirolimus for Kaposi Sarcoma in Renal-Transplant Recipients. Journal Watch Dermatology 2005: 7-7 [Full Text]  
• Dantal, J., Soulillou, J.-P. (2005). Immunosuppressive Drugs and the Risk of Cancer after Organ Transplantation. NEJM 352: 1371-1373 [Full Text]