Everolimus Associated with Activated Vitamin D for Post-Transplant Increase Epstein-Barr-Virus Load Treatment. Two Case Reports

Abstract

Post-transplant lymphoproliferative disease (PTLD) is an uncommon but life-threatening complication of solid-organ and blood stem-cell transplants. It is caused by an uncontrolled expansion of B lymphocytes infected with Epstein-Barr virus (EBV). It responds poorly to therapy, including reduction of immunosuppression, interferon, antivirals or chemotherapy. Therefore the optimal strategy for management is currently focused on prevention. Some centers have already introduced chemoprophylaxis and/or preemptive strategies using EBV viral load as a surveillance. Some experimental studies suggest that mTOR inhibitors inhibits growth of human EBV-transformed B lymphocytes and vitamin D had an immune response to EBV. We report two cases of an increased of blood BKV viral load after renal transplantation that were successfully treated with everolimus in association with calcitriol. This report suggests that everolimus associated with calcitriol could be an effective and safe treatment for the prevention of PTLD in transplant recipients.

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L. Moscarelli and G. Antognoli, "Everolimus Associated with Activated Vitamin D for Post-Transplant Increase Epstein-Barr-Virus Load Treatment. Two Case Reports," International Journal of Clinical Medicine, Vol. 3 No. 7, 2012, pp. 669-672. doi: 10.4236/ijcm.2012.37119.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] S. M. Cockfield, “Identifying the Patient at Risk for Post-Transplant Lymphoproliferative Disorder,” Transplant infectious Disease, Vol. 3, No. 2, 2001, pp. 70-78. doi:10.1034/j.1399-3062.2001.003002070.x
[2] D. A. Thorley-Lawson and A. Gross, “Persistence of the Epstein-Barr Virus and the Origins of Associated Lymphomas,” The New England Journal of Medicine, Vol. 350, No. 13, 2004, pp. 1328-1337. doi:10.1056/NEJMra032015
[3] L. L. Laichalk and D. A. Thorley-Lawson, “Terminal Differentiation into Plasma Cells initiates the Replicative Cycle of Epstein-Barr Virus in Vivo,” Journal of Virology, Vol. 79, No. 2, 2005, pp. 1296-1307. doi:10.1128/JVI.79.2.1296-1307.2005
[4] V. Hadinoto, M. Shapiro, C. C. Sun, et al., “The Dynamics of EBV Shedding Implicate A Central Role for Epithelial Cells in Amplifying Viral Output,” PLoS Pathogens, Vol. 5, No. 7, 2009, p. 1.
[5] A. D. Hislop, G. S. Taylor, D. Sauce, et al., “Cellular Responses to Viral infection in Humans: Lessons from Epstain-Barr Virus,” Annual Reviews of Immunology, Vol. 25, No. 1, 2007, pp. 587-617. doi:10.1146/annurev.immunol.25.022106.141553
[6] A. B. Rickinson and E. Kieff, “Epstein-Barr Virus,” In: D. M. Knipe and P. M. Howley, Eds., Fields Virology, Lippincott Williams & Wilkins, Philadelphia, 2001, pp. 2575-2627.
[7] M. Majewski, M. Korecka, P. kossev, et al., “The Immunosuppressive Macrolide RAD Inhibits Growth of Human Epstein-Barr Virus-Transformed B Lymphocytes in Vitro and in Vivo: A Potential Approach to Prevention and Treatment of Posttransplant Lym-phoproliferative Disorders,” Proceedings of the National Academy of Sciences, Vol. 97, No. 8, 2000, pp. 4285-4290
[8] S. Muthukkumar, T. M. Ramesh and S. Bondada, “Ra- pamycin, a Potent Immunosuppressive Drug, Causes Programmed Cell Death in B Lymphoma Cells,” Transplantation, Vol. 60, No. 3, 1995, pp. 264-270. doi:10.1097/00007890-199508000-00010
[9] S. N. Seghal, J. S. Camardo, J. A. Scarola, et al., “Rapamycin (Sirolimus, Rapamune),” Current Opinion in Nephrology and Hypertension, Vol. 4, No. 6, 1995, pp. 482-487. doi:10.1097/00041552-199511000-00004
[10] T. Hol-moy, “Vitamin D Status Modulates the Immune Response to Epstein Barr Virus: Synergistic Effect of Risk Factors in Multiple Sclerosis,” Medical Hypotheses, Vol. 70, No. 1, 2008, pp. 66-69. doi:10.1016/j.mehy.2007.04.030
[11] Y. Dror, M. Greenberg, G. Taylor, et al., “Lymphoprolif- erative Disorders after Organ Transplantation in Children,” Transplantation, Vol. 67, No. 7, 1999, pp. 990-998. doi:10.1097/00007890-199904150-00010
[12] R. Shapiro, M. Nalesnik, J. Mc Cauley, et al., “Posttrans- plant Lymphoproliferative Disorders in Adult and Pediatric Renal Transplant Patients Receiving Tacrolimus-Based Immunosuppression,” Transplantation, Vol. 68, No. 12, 1999, pp. 1851-1854. doi:10.1097/00007890-199912270-00006
[13] B. S. Younes, S. V. Mc Diarmid, M. G. Martin, et al., “The Effect of Immunosuppression on Posttransplant Lym-phoproliferative Disease in Pediatric Liver Transplant Patients,” Transplantation, Vol. 70, No. 1, 2000, pp. 94-99.
[14] J. K. Preiksaitis and S. Keay, “Diagnosis and Management of Post-Transplant Lymphoproliferative Disorder in Solid-Organ Transplant Recipients,” Clinical Infectious Diseases, Vol. 33, No. S1, 2001, pp. S38-S46.
[15] C. E. Kew, R. Lopez-Ben and J. K. Smith, “Posttrans- plant Lymphoproliferative Disorder Localized near the Allograft in Renal Transplantation,” Transplan-tation, Vol. 69, No. 5, 2000, pp. 809-814.
[16] P. T. Liu, S. Stenger, H. Y. Li, et al., “Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response,” Science, Vol. 311, No. 5768, 2006, pp. 1770-1773.

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