A Survival of Post-transplant Lymphoproliferative Disorder after Kidney Transplantation in Patients under Rapamycin Treatment
-
Farzaneh Ashrafi
,
Shahrzad Shahidi
,
Valiollah Mehrzad
,
Mojgan Mortazavi
,
Sayyiedh Forough Hosseini
Abstract
Background: One of the important causes of mortality and morbidity in kidney transplanted patients is Post Transplant Lymphoproliferative Disease (PTLD), which is due to immunosuppression therapy and viral activity. It seems that Rapamycin, with dual antineoplastic and immunosuppressive effects, may have a pivotal role in the treatment of PTLD patients and preserving transplanted kidneys.
Methods and Materials: Twenty patients with PTLD were enrolled. Immunosuppressive therapy was reduced or ceased, and Rapamycin was initiated at the time of PTLD diagnosis. We evaluated the effects of switching immunosuppressive drugs to Rapamycin on graft status, the response of tumor, and 6, 12 months, and 5-year survival in patients.
Results: PTLD remission was achieved in 14 patients, while six patients died; no relapse was detected in recovered patients. The median of PTLD free time was 25 months, and the mean overall survival in patients with PTLD treated by Rapamycin was 84.8 (95% CI=61.3-108.23).The five-year survival rate was 67%, 12 months survival was 73.8%, and six months' survival was 80%. The response rate to Rapamycin and immunosuppression reduction alone was 46.6%. Four out of 13 Diffuse Large B-Cell Lymphoma patients achieved a complete response just only after the reduction of immunosuppressive drugs and the consumption of Rapamycin.
Conclusion: The present study demonstrated the effectiveness of conversion from immunosuppressive medication, particularly of Calcineurin inhibitors to Rapamycin in PTLD patients. However, more research is needed to confirm the Rapamycin effect on patients with PTLD.
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2.Luskin MR, Heil DS, Tan KS, et al. The Impact of EBV Status on Characteristics and Outcomes of Posttransplantation Lymphoproliferative Disorder. Am J Transplant. 2015;15(10):2665-73.
3.Dierickx D, Tousseyn T, Sagaert X, et al. Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinicopathological characteristics and prognostic factors. Leuk Lymphoma. 2013;54(11):2433-40.
4. Swerdlow S. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours. 2008:285-8.
5.Dierickx D, Tousseyn T, Gheysens O. How I treat posttransplant lymphoproliferative disorders. Blood. 2015;126(20):2274-83.
6.Opelz G, Döhler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant. 2004;4(2):222-30.
7.Garcia VD, Bonamigo Filho JL, Neumann J, et al. Rituximab in association with rapamycin for post-transplant lymphoproliferative disease treatment. Transpl Int. 2003;16(3):202-6.
8.Kasiske BL, Snyder JJ, Gilbertson DT, et al. Cancer after kidney transplantation in the United States. Am J Transplant. 2004;4(6):905-13.
9.Cheung CY, Ma MKM, Chau KF, et al. Posttransplant lymphoproliferative disorders in kidney transplant recipients: a retrospective cohort analysis over two decades in Hong Kong. Oncotarget. 2017;8(57):96903-12.
10.Tsai DE, Hardy CL, Tomaszewski JE, et al. Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients. Transplantation. 2001;71(8):1076-88.
11.Majewski M, Korecka M, Kossev P, 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 lymphoproliferative disorders. Proc Natl Acad Sci U S A. 2000;97(8):4285-90.
12.Majewski M, Korecka M, Joergensen J, et al. Immunosuppressive TOR kinase inhibitor everolimus (RAD) suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses. Transplantation. 2003;75(10):1710-7.
13.Ashrafi F, Shahidi S, Ebrahimi Z, et al. Outcome of rapamycin therapy for post-transplant-lymphoproliferative disorder after kidney transplantation: case series. Int J Hematol Oncol Stem Cell Res. 2015;9(1):26-32.
14.Yakupoglu YK, Buell JF, Woodle S, et al. Individualization of Immunosuppressive Therapy. III. Sirolimus Associated With a Reduced Incidence of Malignancy. Transplant Proc. 2006;38(2):358-61.
15.Koehl G, Guba M, Seeliger H, et al. Rapamycin treatment at immunosuppressive doses affects tumor blood vessel circulation. Transplant Proc. 2003;35(6):2135-6.
16.Campistol JM, Eris J, Oberbauer R, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol. 2006;17(2):581-9.
17.Iaria G, Anselmo A, De Luca L, et al. Conversion to rapamycin immunosuppression for malignancy after kidney transplantation: case reports. Transplant Proc. 2007;39(6):2036-7.
18.Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med. 2005;352(13):1317-23.
19.Cullis B, D'Souza R, McCullagh P, et al. Sirolimus-induced remission of posttransplantation lymphoproliferative disorder. Am J Kidney Dis. 2006;47(5):e67-72.
20.Armitage JM, Kormos RL, Stuart RS, et al. Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression. J Heart Lung Transplant. 1991;10(6):877-86; discussion 86-7.
21.Starzl TE, Nalesnik MA, Porter KA, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet. 1984;1(8377):583-7.
22.Nalesnik MA, Jaffe R, Starzl TE, et al. The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression. Am J Pathol. 1988;133(1):173-92.
23.Chen JM, Barr ML, Chadburn A, et al. Management of lymphoproliferative disorders after cardiac transplantation. Ann Thorac Surg. 1993;56(3):527-38.
24.Morton M, Coupes B, Roberts SA, et al. Epidemiology of posttransplantation lymphoproliferative disorder in adult renal transplant recipients. Transplantation. 2013;95(3):470-8.
25.Dotti G, Fiocchi R, Motta T, et al. Lymphomas occurring late after solid-organ transplantation: influence of treatment on the clinical outcome. Transplantation. 2002;74(8):1095-102.
26.Pascual J. Post-transplant lymphoproliferative disorder--the potential of proliferation signal inhibitors. Nephrol Dial Transplant. 2007;22 Suppl 1:i27-35.
27. International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329(14):987-94.
28.Caillard S, Porcher R, Provot F, et al. Post-transplantation lymphoproliferative disorder after kidney transplantation: report of a nationwide French registry and the development of a new prognostic score. J Clin Oncol. 2013;31(10):1302-9.
29.Tsao L, Hsi ED. The clinicopathologic spectrum of posttransplantation lymphoproliferative disorders. Arch Pathol Lab Med. 2007;131(8):1209-18.
30.Caillard S, Lamy FX, Quelen C, et al. Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas. Am J Transplant. 2012;12(3):682-93.
31.Leblond V, Dhedin N, Mamzer Bruneel MF, et al. Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders. J Clin Oncol. 2001;19(3):772-8.
32.Trappe R, Oertel S, Leblond V, et al. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012;13(2):196-206.
33.Oertel SH, Verschuuren E, Reinke P, et al. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD). Am J Transplant. 2005;5(12):2901-6.
34.Chen W, Huang Q, Zuppan CW, et al. Complete absence of KSHV/HHV-8 in posttransplant lymphoproliferative disorders: an immunohistochemical and molecular study of 52 cases. Am J Clin Pathol. 2009;131(5):632-9.
35.Kapelushnik J, Ariad S, Benharroch D, et al. Post renal transplantation human herpesvirus 8-associated lymphoproliferative disorder and Kaposi's sarcoma. Br J Haematol.2001;113(2):425-8.
36.Zallio F, Primon V, Tamiazzo S, et al. Epstein–Barr virus reactivation in allogeneic stem cell transplantation is highly related to cytomegalovirus reactivation. Clin Transplant. 2013;27(4):E491-E7.
37.Lazarovits AI, Tibbles LA, Grant DR, et al. Anti-B cell antibodies for the treatment of monoclonal Epstein-Barr virus-induced lymphoproliferative syndrome after multivisceral transplantation. Clin Invest Med. 1994;17(6):621-5.
2.Luskin MR, Heil DS, Tan KS, et al. The Impact of EBV Status on Characteristics and Outcomes of Posttransplantation Lymphoproliferative Disorder. Am J Transplant. 2015;15(10):2665-73.
3.Dierickx D, Tousseyn T, Sagaert X, et al. Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinicopathological characteristics and prognostic factors. Leuk Lymphoma. 2013;54(11):2433-40.
4. Swerdlow S. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours. 2008:285-8.
5.Dierickx D, Tousseyn T, Gheysens O. How I treat posttransplant lymphoproliferative disorders. Blood. 2015;126(20):2274-83.
6.Opelz G, Döhler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant. 2004;4(2):222-30.
7.Garcia VD, Bonamigo Filho JL, Neumann J, et al. Rituximab in association with rapamycin for post-transplant lymphoproliferative disease treatment. Transpl Int. 2003;16(3):202-6.
8.Kasiske BL, Snyder JJ, Gilbertson DT, et al. Cancer after kidney transplantation in the United States. Am J Transplant. 2004;4(6):905-13.
9.Cheung CY, Ma MKM, Chau KF, et al. Posttransplant lymphoproliferative disorders in kidney transplant recipients: a retrospective cohort analysis over two decades in Hong Kong. Oncotarget. 2017;8(57):96903-12.
10.Tsai DE, Hardy CL, Tomaszewski JE, et al. Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients. Transplantation. 2001;71(8):1076-88.
11.Majewski M, Korecka M, Kossev P, 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 lymphoproliferative disorders. Proc Natl Acad Sci U S A. 2000;97(8):4285-90.
12.Majewski M, Korecka M, Joergensen J, et al. Immunosuppressive TOR kinase inhibitor everolimus (RAD) suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses. Transplantation. 2003;75(10):1710-7.
13.Ashrafi F, Shahidi S, Ebrahimi Z, et al. Outcome of rapamycin therapy for post-transplant-lymphoproliferative disorder after kidney transplantation: case series. Int J Hematol Oncol Stem Cell Res. 2015;9(1):26-32.
14.Yakupoglu YK, Buell JF, Woodle S, et al. Individualization of Immunosuppressive Therapy. III. Sirolimus Associated With a Reduced Incidence of Malignancy. Transplant Proc. 2006;38(2):358-61.
15.Koehl G, Guba M, Seeliger H, et al. Rapamycin treatment at immunosuppressive doses affects tumor blood vessel circulation. Transplant Proc. 2003;35(6):2135-6.
16.Campistol JM, Eris J, Oberbauer R, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol. 2006;17(2):581-9.
17.Iaria G, Anselmo A, De Luca L, et al. Conversion to rapamycin immunosuppression for malignancy after kidney transplantation: case reports. Transplant Proc. 2007;39(6):2036-7.
18.Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med. 2005;352(13):1317-23.
19.Cullis B, D'Souza R, McCullagh P, et al. Sirolimus-induced remission of posttransplantation lymphoproliferative disorder. Am J Kidney Dis. 2006;47(5):e67-72.
20.Armitage JM, Kormos RL, Stuart RS, et al. Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression. J Heart Lung Transplant. 1991;10(6):877-86; discussion 86-7.
21.Starzl TE, Nalesnik MA, Porter KA, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet. 1984;1(8377):583-7.
22.Nalesnik MA, Jaffe R, Starzl TE, et al. The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression. Am J Pathol. 1988;133(1):173-92.
23.Chen JM, Barr ML, Chadburn A, et al. Management of lymphoproliferative disorders after cardiac transplantation. Ann Thorac Surg. 1993;56(3):527-38.
24.Morton M, Coupes B, Roberts SA, et al. Epidemiology of posttransplantation lymphoproliferative disorder in adult renal transplant recipients. Transplantation. 2013;95(3):470-8.
25.Dotti G, Fiocchi R, Motta T, et al. Lymphomas occurring late after solid-organ transplantation: influence of treatment on the clinical outcome. Transplantation. 2002;74(8):1095-102.
26.Pascual J. Post-transplant lymphoproliferative disorder--the potential of proliferation signal inhibitors. Nephrol Dial Transplant. 2007;22 Suppl 1:i27-35.
27. International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329(14):987-94.
28.Caillard S, Porcher R, Provot F, et al. Post-transplantation lymphoproliferative disorder after kidney transplantation: report of a nationwide French registry and the development of a new prognostic score. J Clin Oncol. 2013;31(10):1302-9.
29.Tsao L, Hsi ED. The clinicopathologic spectrum of posttransplantation lymphoproliferative disorders. Arch Pathol Lab Med. 2007;131(8):1209-18.
30.Caillard S, Lamy FX, Quelen C, et al. Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas. Am J Transplant. 2012;12(3):682-93.
31.Leblond V, Dhedin N, Mamzer Bruneel MF, et al. Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders. J Clin Oncol. 2001;19(3):772-8.
32.Trappe R, Oertel S, Leblond V, et al. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012;13(2):196-206.
33.Oertel SH, Verschuuren E, Reinke P, et al. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD). Am J Transplant. 2005;5(12):2901-6.
34.Chen W, Huang Q, Zuppan CW, et al. Complete absence of KSHV/HHV-8 in posttransplant lymphoproliferative disorders: an immunohistochemical and molecular study of 52 cases. Am J Clin Pathol. 2009;131(5):632-9.
35.Kapelushnik J, Ariad S, Benharroch D, et al. Post renal transplantation human herpesvirus 8-associated lymphoproliferative disorder and Kaposi's sarcoma. Br J Haematol.2001;113(2):425-8.
36.Zallio F, Primon V, Tamiazzo S, et al. Epstein–Barr virus reactivation in allogeneic stem cell transplantation is highly related to cytomegalovirus reactivation. Clin Transplant. 2013;27(4):E491-E7.
37.Lazarovits AI, Tibbles LA, Grant DR, et al. Anti-B cell antibodies for the treatment of monoclonal Epstein-Barr virus-induced lymphoproliferative syndrome after multivisceral transplantation. Clin Invest Med. 1994;17(6):621-5.
| Files | ||
| Issue | Vol 15, No 4 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v15i4.7479 | |
| Keywords | ||
| Rapamycin; Post-transplant lymphoproliferative disorders; Renal transplant M-TOR inhibitors; Lymphoma | ||
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How to Cite
1.
Ashrafi F, Shahidi S, Mehrzad V, Mortazavi M, Hosseini SF. A Survival of Post-transplant Lymphoproliferative Disorder after Kidney Transplantation in Patients under Rapamycin Treatment. Int J Hematol Oncol Stem Cell Res. 2021;15(4):239-248.
