Posttransplant Lymphoproliferative Disorder after Cardiac Transplantation in Children: Life Threatening Complications Associated with Chemotherapy Combined with Rituximab
Despite the excellent long-term survival currently achieved in pediatric heart transplant recipients, posttransplant lymphoproliferative disorders (PTLDs) are one of the most important causes of morbidity and mortality after heart transplantation (HTx), especially in children. Timely and accurate diagnosis based on histological examination of biopsy tissue is essential for early intervention for PTLD. Chemotherapy is indicated for patients with poor response to reduction of immunosuppressive medication and for highly aggressive monomorphic PTLD. The use of rituximab in combination with chemotherapy is effective to suppress B cell type PTLD (B-PTLD). However, PTLD relapses frequently and the outcome is still poor. Although everolimus (EVL) has been reported to inhibit growth of human Epstein-Barr-virus- (EBV-) transformed B lymphocytes in vitro and in vivo, EVL has several side effects, such as delayed wound healing and an increase in bacterial infection. During combined treatment of chemotherapy and rituximab, B-PTLDs are sometimes associated with life-threatening complications, such as intestinal perforation and cardiogenic shock due to cytokine release syndrome. In HTx children especially treated with EVL, stoma should be made to avoid reoperation or sepsis in case of intestinal perforation. In cases with cardiac graft dysfunction possibly due to cytokine release syndrome by chemotherapy with rituximab for PTLD, plasma exchange is effective to restore cardiac function and to rescue the patients. 1. Introduction More than five hundred heart transplants (HTx) in children (<18 years age) had been performed every year in the world since 2008 [1]. Despite the excellent long-term survival currently achieved in children who underwent HTx, the immunosuppressive medications required to prevent allograft rejection throughout his or her life may cause significant morbidity and mortality, such as malignancy, renal dysfunction, hypertension, hyperlipidemia, and diabetes mellitus. Although most malignancies in adults are skin cancers [2], almost all malignancies are posttransplant lymphoproliferative disorders (PTLD) in children [1]. PTLD is counted as the cause of death in 2.0%, 3.3%, 4.1%, 8.4%, and 8.2% of cases in the period from 31 days to 1 year, <1–3 years, <3–5 years, <5–10 years, and >10 years after HTx, respectively [1]. PTLD has a wide spectrum of disease manifestations, ranging from a benign plasmacytic hyperplasia and infectious mononucleosis-like PTLD (so called early lesion) to an aggressive monoclonal lymphoma (such as Burkitt lymphoma) that can be
References
[1]
R. Kirk, A. I. Dipchand, L. B. Edwards, et al., “Registry of the The Registry of the International Society for Heart and Lung Transplantation: Fifteenth Pediatric Heart Transplantation Report-2012,” http://www.jhltonline.org/.
[2]
J. Stehlik, L. B. Edwards, A. Y. Kucheryvaya, et al., “The Registry of the International Society for Heart and Lung Transplantation: 29th Official Adult Heart Transplant Report-2012,” The Journal of Heart and Lung Transplantation, vol. 31, no. 10, pp. 1052–1064, 2012.
[3]
G. Végso, M. Hajdu, and A. Sebestyén, “Lymphoproliferative disorders after solid organ transplantation-classification, incidence, risk factors, early detection and treatment options,” Pathology and Oncology Research, vol. 17, no. 3, pp. 443–454, 2011.
[4]
O. Kollmar, S. Becker, M. K. Schilling, and C. A. Maurer, “Intestinal lymphoma perforations as a consequence of highly effective anti-CD20 antibody therapy,” Transplantation, vol. 73, no. 4, pp. 669–670, 2002.
[5]
J. C. Byrd, J. K. Waselenko, T. J. Maneatis et al., “Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance,” Journal of Clinical Oncology, vol. 17, no. 3, pp. 791–795, 1999.
[6]
S.-J. Wu, W.-C. Chou, B.-S. Ko, and H.-F. Tien, “Severe pulmonary complications after initial treatment with rituximab for the Asian-variant of intravascular lymphoma,” Haematologica, vol. 92, no. 1, pp. 141–142, 2007.
[7]
P. M. Millward, N. Bandarenko, P. P. Chang et al., “Cardiogenic shock complicates successful treatment of refractory thrombotic thrombocytopenia purpura with rituximab,” Transfusion, vol. 45, no. 9, pp. 1481–1486, 2005.
[8]
J. O. Armitage, “Staging non-Hodgkin lymphoma,” Ca-A Cancer Journal for Clinicians, vol. 55, no. 6, pp. 368–376, 2005.
[9]
G. Opelz and B. D？hler, “Lymphomas after solid organ transplantation: a collaborative transplant study report,” American Journal of Transplantation, vol. 4, no. 2, pp. 222–230, 2004.
[10]
A. L. Taylor, R. Marcus, and J. A. Bradley, “Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation,” Critical Reviews in Oncology/Hematology, vol. 56, no. 1, pp. 155–167, 2005.
[11]
S. A. Webber, D. C. Naftel, F. J. Fricker et al., “Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study,” The Lancet, vol. 367, no. 9506, pp. 233–239, 2006.
[12]
M. Ross, P. Kouretas, P. Gamberg et al., “Ten- and 20-year survivors of pediatric orthotopic heart transplantation,” The Journal of Heart and Lung Transplantation, vol. 25, no. 3, pp. 261–270, 2006.
[13]
S.-Z. Gao, S. V. Chaparro, M. Perlroth et al., “Post-transplantation lymphoproliferative disease in heart and heart-lung transplant recipients: 30-Year experience at Stanford University,” The Journal of Heart and Lung Transplantation, vol. 22, no. 5, pp. 505–514, 2003.
[14]
R. Chinnock, S. A. Webber, A. I. Dipchand, et al., “A 16-year multi-institutional study of the Role of age and EBV status on PTLD incidence among pediatric heart transplant recipients,” American Journal of Transplantation, vol. 12, pp. 3061–3068, 2012.
[15]
C. Benden, L. B. Edwards, A. Y. Kucheryavaya, et al., “The Registry of the International Society for Heart and Lung Transplantation: Fifteenth Pediatric Lung and Heart-Lung Transplantation Report-2012,” The Journal of Heart and Lung Transplantation, vol. 31, no. 10, pp. 1087–1095, 2012.
[16]
L. Tsao and E. D. Hsi, “The clinicopathologic spectrum of posttransplantation lymphoproliferative disorders,” Archives of Pathology and Laboratory Medicine, vol. 131, no. 8, pp. 1209–1218, 2007.
[17]
J. F. George, S. V. Pamboukian, J. A. Tallaj et al., “Balancing rejection and infection with respect to age, race, and gender: clues acquired from 17 years of cardiac transplantation data,” The Journal of Heart and Lung Transplantation, vol. 29, no. 9, pp. 966–972, 2010.
[18]
N. A. Bakker, G. W. Van Imhoff, E. A. M. Verschuuren, and W. J. Van Son, “Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation,” Transplant International, vol. 20, no. 3, pp. 207–218, 2007.
[19]
A. W. Loren, D. L. Porter, E. A. Stadtmauer, and D. E. Tsai, “Post-transplant lymphoproliferative disorder: a review,” Bone Marrow Transplantation, vol. 31, no. 3, pp. 145–155, 2003.
[20]
J. F. George, D. O. Taylor, E. D. Blume et al., “Minimizing infection and rejection death: clues acquired from 19 years of multi-institutional cardiac transplantation data,” The Journal of Heart and Lung Transplantation, vol. 30, no. 2, pp. 151–157, 2011.
[21]
R. Kirk, L. B. Edwards, A. Y. Kucheryavaya et al., “The Registry of the International Society for Heart and Lung Transplantation: Thirteenth official pediatric heart transplantation report-2010,” The Journal of Heart and Lung Transplantation, vol. 29, no. 10, pp. 1119–1128, 2010.
[22]
C. Benden, P. Aurora, M. Burch et al., “Monitoring of Epstein-Barr viral load in pediatric heart and lung transplant recipients by real-time polymerase chain reaction,” The Journal of Heart and Lung Transplantation, vol. 24, no. 12, pp. 2103–2108, 2005.
[23]
S. Schubert, C. Renner, M. Hammer et al., “Relationship of immunosuppression to Epstein–Barr viral load and lymphoproliferative disease in pediatric heart transplant patients,” The Journal of Heart and Lung Transplantation, vol. 27, no. 1, pp. 100–105, 2008.
[24]
S. Schubert, H. Abdul-Khaliq, H. B. Lehmkuhl et al., “Diagnosis and treatment of post-transplantation lymphoproliferative disorder in pediatric heart transplant patients,” Pediatric Transplantation, vol. 13, no. 1, pp. 54–62, 2009.
[25]
M. Green, M. G. Michaels, B. Z. Katz et al., “CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients,” American Journal of Transplantation, vol. 6, no. 8, pp. 1906–1912, 2006.
[26]
M. Green, J. Bueno, D. Rowe et al., “Predictive negative value of persistent low Epstein-Barr virus viral load after intestinal transplantation in children,” Transplantation, vol. 70, no. 4, pp. 593–596, 2000.
[27]
M. A. Bingler, B. Feingold, S. A. Miller et al., “Chronic high Epstein-Barr viral load state and risk for late-onset posttransplant lymphoproliferative disease/lymphoma in children,” American Journal of Transplantation, vol. 8, no. 2, pp. 442–445, 2008.
[28]
R. Scheenstra, E. A. M. Verschuuren, A. De Haan et al., “The value of prospective monitoring of Epstein-Barr virus DNA in blood samples of pediatric liver transplant recipients,” Transplant Infectious Disease, vol. 6, no. 1, pp. 15–22, 2004.
[29]
D. A. Axelrod, R. Holmes, S. E. Thomas, and J. C. Magee, “Limitations of EBV-PCR monitoring to detect EBV associated post-transplant lymphoproliferative disorder,” Pediatric Transplantation, vol. 7, no. 3, pp. 223–227, 2003.
[30]
L. J. Swinnen, M. R. Costanzo-Nordin, S. G. Fisher et al., “Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients,” New England Journal of Medicine, vol. 323, no. 25, pp. 1723–1728, 1990.
[31]
J. D. Dayton, M. E. Richmond, R. G. Weintraub, A. T. Shipp, M. Orjuela, and L. J. Addonizio, “Role of immunosuppression regimen in post-transplant lymphoproliferative disorder in pediatric heart transplant patients,” The Journal of Heart and Lung Transplantation, vol. 30, no. 4, pp. 420–425, 2011.
[32]
R. J. Gajarski, E. D. Blume, S. Urschel et al., “Infection and malignancy after pediatric heart transplantation: the role of induction therapy,” The Journal of Heart and Lung Transplantation, vol. 30, no. 3, pp. 299–308, 2011.
[33]
C. Manlhiot, S. M. Pollock-BarZiv, C. Holmes et al., “Post-transplant lymphoproliferative disorder in pediatric heart transplant recipients,” The Journal of Heart and Lung Transplantation, vol. 29, no. 6, pp. 648–657, 2010.
[34]
K. L. Cox, L. S. Lawrence-Miyasaki, R. Garcia-Kennedy et al., “An increased incidence of Epstein-Barr virus infection and lymphoproliferative disorder in young children on FK506 after liver transplantation,” Transplantation, vol. 59, no. 4, pp. 524–529, 1995.
[35]
S. Cao, K. L. Cox, W. Berquist et al., “Long-term outcomes in pediatric liver recipients: comparison between cyclosporin A and tacrolimus,” Pediatric Transplantation, vol. 3, no. 1, pp. 22–26, 1999.
[36]
B. S. Younes, S. V. McDiarmid, M. G. Martin et al., “The effect of immunosuppression on posttransplant lymphoproliferative disease in pediatric transplant patients,” Transplantation, vol. 70, no. 1, pp. 94–99, 2000.
[37]
V. R. Dharnidharka, P.-L. Ho, D. M. Stablein, W. E. Harmon, and A. H. Tejani, “Mycophenolate, tacrolimus and posttransplant lymphoproliferative disorder: a report of the North American Pediatric Renal Transplant Cooperative Study,” Pediatric Transplantation, vol. 6, no. 5, pp. 396–399, 2002.
[38]
S. Caillard, V. Dharnidharka, L. Agodoa, E. Bohen, and K. Abbott, “Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression,” Transplantation, vol. 80, no. 9, pp. 1233–1243, 2005.
[39]
B. D. Kahan, Y. K. Yakupoglu, L. Schoenberg et al., “Low incidence of malignancy among sirolimus/cyclosporine-treated renal transplant recipients,” Transplantation, vol. 80, no. 6, pp. 749–758, 2005.
[40]
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 lymphoproliferative disorders,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 8, pp. 4285–4290, 2000.
[41]
M. Majewski, M. Korecka, J. Joergensen et al., “Immunosuppressive tor kinase inhibitor everolimus (RAD) suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses,” Transplantation, vol. 75, no. 10, pp. 1710–1717, 2003.
[42]
M. A. Nalesnik, A. Zeevi, P. S. Randhawa et al., “Cytokine mRNA profiles in Epstein-Barr virus-associated post-transplant lymphoproliferative disorders,” Clinical Transplantation, vol. 13, no. 1, pp. 39–44, 1999.
[43]
N. Sculerati and M. Arriaga, “Otolaryngologic management of posttransplant lymphoproliferative disease in children,” Annals of Otology, Rhinology and Laryngology, vol. 99, no. 6, pp. 445–450, 1990.
[44]
S. D. Zangwill, D. T. Hsu, M. R. Kichuk et al., “Incidence and outcome of primary Epstein-Barr virus infection and lymphoproliferative disease in pediatric heart transplant recipients,” The Journal of Heart and Lung Transplantation, vol. 17, no. 12, pp. 1161–1166, 1998.
[45]
C. C. Tai, J. L. Curtis, J. R. Szmuszkovicz et al., “Abdominal involvement in pediatric heart and lung transplant recipients with posttransplant lymphoproliferative disease increases the risk of mortality,” Journal of Pediatric Surgery, vol. 43, no. 12, pp. 2174–2177, 2008.
[46]
T. G. Gross, J. C. Bucuvalas, J. R. Park et al., “Low-dose chemotherapy for Epstein-Barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation,” Journal of Clinical Oncology, vol. 23, no. 27, pp. 6481–6488, 2005.
[47]
L. J. Addonizio and G. J. Boyle, “Posttransplant malignancy: risk, factors, incidence, diagnosis, treatment,” in Pediatric Heart Transplantation, C. E. Canter and J. K. Kirklin, Eds., vol. 2, Elsevier, Philadelphia, Pa, USA, 2007.
[48]
K. Kawa, A. Sawada, M. Koyama, and M. Inoue, “Epstein-Barr virus infection after unrelated cord blood transplantation: reactivation or reinfection?” International Journal of Hematology, vol. 85, no. 3, pp. 267–269, 2007.
[49]
A. Karras, E. Thervet, and C. Legendre, “Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature,” Transplantation, vol. 77, no. 2, pp. 238–243, 2004.
[50]
N. Awaya, A. Adachi, T. Mori et al., “Fulminant Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder with hemophagocytosis following autologous peripheral blood stem cell transplantation for relapsed angioimmunoblastic T-cell lymphoma,” Leukemia Research, vol. 30, no. 8, pp. 1059–1062, 2006.
[51]
H. Chisuwa, Y. Hashikura, Y. Nakazawa et al., “Fatal hemophagocytic syndrome after living-related liver transplantation,” Transplantation, vol. 72, no. 11, pp. 1843–1846, 2001.
[52]
M. Green, M. G. Michaels, S. A. Webber, D. Rowe, and J. Reyes, “The management of Epstein-Barr virus associated post-transplant lymphoproliferative disorders in pediatric solid-organ transplant recipients,” Pediatric Transplantation, vol. 3, no. 4, pp. 271–281, 1999.
[53]
D. M. Walling, L. A. Andritsos, W. Etienne et al., “Molecular markers of clonality and identity in Epstein-Barr virus-associated B-cell lymphoproliferative disease,” Journal of Medical Virology, vol. 74, no. 1, pp. 94–101, 2004.
[54]
W. A. Mourad, A. Tulabah, A. Al Sayed et al., “The impact of the World Health Organization classification and clonality assessment of posttransplant lymphoproliferative disorders on disease management,” Archives of Pathology and Laboratory Medicine, vol. 130, no. 11, pp. 1649–1653, 2006.
[55]
S. B. Murphy, “Classification, staging and end results of treatment of childhood non-Hodgkin's lymphomas: dissimilarities from lymphomas in adults,” Seminars in Oncology, vol. 7, no. 3, pp. 332–339, 1980.
[56]
C. Divgi, “Imaging: staging and evaluation of lymphoma using nuclear medicine,” Seminars in Oncology, vol. 32, no. 1, pp. S11–S18, 2005.
[57]
V. Graute, N. Jansen, H. Sohn, et al., “Diagnostic role of whole-body 18F-FDG positron emission tomography in patients with symptoms suspicious for malignancy after heart transplantation,” The Journal of Heart and Lung Transplantation, vol. 31, pp. 958–966, 2012.
[58]
C. von Falck, B. Maecker, E. Schirg et al., “Post transplant lymphoproliferative disease in pediatric solid organ transplant patients: a possible role for [18F]-FDG-PET(/CT) in initial staging and therapy monitoring,” European Journal of Radiology, vol. 63, no. 3, pp. 427–435, 2007.
[59]
E. Bianchi, M. Pascual, M. Nicod, A. B. Delaloye, and M. A. Duchosal, “Clinical usefulness of FDG-PET/CT scan imaging in the management of posttransplant lymphoproliferative disease,” Transplantation, vol. 85, no. 5, pp. 707–712, 2008.
[60]
M.-K. Song, J.-S. Chung, H.-J. Shin et al., “Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement,” Annals of Hematology, vol. 91, pp. 697–703, 2012.
[61]
D. E. Spratt, R. Diaz, J. McElmurray et al., “Impact of FDG PET/CT on delineation of the gross tumor volume for radiation planning in non-small-cell lung cancer,” Clinical Nuclear Medicine, vol. 35, no. 4, pp. 237–243, 2010.
[62]
T. H. La, E. J. Filion, B. B. Turnbull et al., “Metabolic tumor volume predicts for recurrence and death in head-and-neck cancer,” International Journal of Radiation Oncology Biology Physics, vol. 74, no. 5, pp. 1335–1341, 2009.
[63]
P. S. Randhawa, R. Jaffe, A. J. Demetris et al., “Expression of Epstein-Barr virus-encoded small RNA (by the EBER-1 gene) in liver specimens from transplant recipients with post-transplantation lymphoproliferative disease,” New England Journal of Medicine, vol. 327, no. 24, pp. 1710–1714, 1992.
[64]
H.-J. Delecluse, E. Kremmer, J.-P. Rouault, C. Cour, G. Bornkamm, and F. Berger, “The expression of Epstein-Barr virus latent proteins is related to the pathological features of post-transplant lymphoproliferative disorders,” American Journal of Pathology, vol. 146, no. 5, pp. 1113–1120, 1995.
[65]
R. Shaknovich, K. Basso, G. Bhagat et al., “Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling,” Haematologica, vol. 91, no. 10, pp. 1313–1320, 2006.
[66]
N. L. Harris, E. S. Jaffe, J. Diebold et al., “The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997,” Histopathology, vol. 36, no. 1, pp. 69–87, 2000.
[67]
N. L. Harris, S. H. Swerdlow, G. Frizzera, et al., “Posttransplant lymphoproliferative disorders,” in World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissue, E. S. Jaffe, N. L. Harris, H. Stein, and J. W. Vardiman, Eds., pp. 264–269, IARC Press, Lyon, France, 2001.
[68]
S. H. Swerdlow, S. A. Webber, A. Chadburn, et al., “Posttransplant lymphoproliferative disorders (PTLD),” in WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue, pp. 343–350, IARC Press, Lyon, France, 2008.
[69]
K. Mucha, B. Foroncewicz, B. Ziarkiewicz-Wróblewska, M. Krawczyk, J. Lerut, and L. Pczek, “Post-transplant lymphoproliferative disorder in view of the new WHO classification: a more rational approach to a protean disease?” Nephrology Dialysis Transplantation, vol. 25, no. 7, pp. 2089–2098, 2010.
[70]
A. Parker, K. Bowles, J. A. Bradley et al., “Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients—BCSH and BTS Guidelines,” British Journal of Haematology, vol. 149, no. 5, pp. 675–692, 2010.
[71]
Y. Hoshida, T. Li, Z. Dong, et al., “Lymphoproliferative disorders in renal transplant patients in Japan,” International Journal of Cancer, vol. 91, pp. 869–875, 2001.
[72]
M. Benkerrou, A. Durandy, and A. Fischer, “Therapy for transplant-related lymphoproliferative diseases,” Hematology/Oncology Clinics of North America, vol. 7, no. 2, pp. 467–475, 1993.
[73]
T. V. Cacciarelli, M. Green, R. Jaffe et al., “Management of posttransplant lymphoproliferative disease in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy,” Transplantation, vol. 66, no. 8, pp. 1047–1052, 1998.
[74]
K. A. Newell, E. M. Alonso, P. F. Whitington et al., “Posttransplant lymphoproliferative disease in pediatric liver transplantation: interplay between primary Epstein-Barr virus infection and immunosuppression,” Transplantation, vol. 62, no. 3, pp. 370–375, 1996.
[75]
M. M. Boucek, C. M. Mathis, M. S. Kanakriyeh, D. D. Hodgkin, R. J. Boucek Jr., and L. L. Bailey, “Serial echocardiographic evaluation of cardiac graft rejection after infant heart transplantation,” The Journal of Heart and Lung Transplantation, vol. 12, no. 5, pp. 824–831, 1993.
[76]
R. R. Nepomuceno, C. E. Balatoni, Y. Natkunam, A. L. Snow, S. M. Krams, and O. M. Martinez, “Rapamycin inhibits the interleukin 10 signal transduction pathway and the growth of Epstein Barr virus B-cell lymphomas,” Cancer Research, vol. 63, no. 15, pp. 4472–4480, 2003.
[77]
M. El-Salem, P. N. Raghunath, M. Marzec et al., “Constitutive activation of mTOR signaling pathway in post-transplant lymphoproliferative disorders,” Laboratory Investigation, vol. 87, no. 1, pp. 29–39, 2007.
[78]
J. Pascual, “Post-transplant lymphoproliferative disorder—the potential of proliferation signal inhibitors,” Nephrology Dialysis Transplantation, vol. 22, supplement 1, pp. i27–i35, 2007.
[79]
J. A. Sánchez-Brotons, J. M. Sobrino-Márquez, E. Lage-Gallé et al., “Preliminary experience with conversion from calcineurin inhibitors to everolimus in cardiac transplantation maintenance therapy,” Transplantation Proceedings, vol. 40, no. 9, pp. 3046–3048, 2008.
[80]
A. O. Zuckermann and A. Z. Aliabadi, “Calcineurin-inhibitor minimization protocols in heart transplantation,” Transplant International, vol. 22, no. 1, pp. 78–89, 2009.
[81]
C. Jiménez-Rivera, Y. Avitzur, A. H. Fecteau, N. Jones, D. Grant, and V. L. Ng, “Sirolimus for pediatric liver transplant recipients with post-transplant lymphoproliferative disease and hepatoblastoma,” Pediatric Transplantation, vol. 8, no. 3, pp. 243–248, 2004.
[82]
S. Kusuki, Y. Hashii, N. Fukushima et al., “Pediatric post-transplant diffuse large B cell lymphoma after cardiac transplantation,” International Journal of Hematology, vol. 89, no. 2, pp. 209–213, 2009.
[83]
G. Muti, S. Cantoni, P. Oreste et al., “Post-transplant lymphoproliferative disorders: improved outcome after clinico-pathologically tailored treatment,” Haematologica, vol. 87, no. 1, pp. 67–77, 2002.
[84]
R. L. Elstrom, C. Andreadis, N. A. Aqui et al., “Treatment of PTLD with rituximab or chemotherapy,” American Journal of Transplantation, vol. 6, no. 3, pp. 569–576, 2006.
[85]
M. D. Pescovitz, “The use of rituximab, anti-CD20 monoclonal antibody, in pediatric transplantation,” Pediatric Transplantation, vol. 8, no. 1, pp. 9–21, 2004.
[86]
V. Ganne, N. Siddiqi, B. Kamaplath et al., “Humanized anti-CD20 monoclonal antibody (Rituximab) treatment for post-transplant lymphoproliferative disorder,” Clinical Transplantation, vol. 17, no. 5, pp. 417–422, 2003.
[87]
S. Choquet, V. Leblond, R. Herbrecht et al., “Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study,” Blood, vol. 107, no. 8, pp. 3053–3057, 2006.
[88]
A. H. Blaes, B. A. Peterson, N. Bartlett, D. L. Dunn, and V. A. Morrison, “Rituximab therapy is effective for posttransplant lymphoproliferative disorders after solid organ transplantation: results of a phase II trial,” Cancer, vol. 104, no. 8, pp. 1661–1667, 2005.
[89]
B. Coiffier, E. Lepage, J. Brière et al., “Chop chemotherapy plus rituximab compared with chop alone in elderly patients with diffuse large-B-cell lymphoma,” New England Journal of Medicine, vol. 346, no. 4, pp. 235–242, 2002.
[90]
N. Mounier, J. Briere, C. Gisselbrecht et al., “Rituximab plus CHOP (R-CHOP) overcomes bcl-2-associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL),” Blood, vol. 101, no. 11, pp. 4279–4284, 2003.
[91]
R. U. Trappe, S. Choquet, P. Reinke et al., “Salvage therapy for relapsed posttransplant lymphoproliferative disorders (PTLD) with a second progression of PTLD after upfront chemotherapy: the role of single-agent rituximab,” Transplantation, vol. 84, no. 12, pp. 1708–1712, 2007.
[92]
K. Fu, D. D. Weisenburger, W. W. L. Choi et al., “Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma,” Journal of Clinical Oncology, vol. 26, no. 28, pp. 4587–4594, 2008.
[93]
M. Orjuela, T. G. Gross, Y.-K. Cheung, B. Alobeid, E. Morris, and M. S. Cairo, “A pilot study of chemoimmunotherapy (cyclophosphamide, prednisone, and rituximab) in patients with post-transplant lymphoproliferative disorder following solid organ transplantation,” Clinical Cancer Research, vol. 9, no. 10, pp. 3945S–3952S, 2003.
[94]
C. Ara, S. Coban, C. Kayaalp, S. Yilmaz, and V. Kirimlioglu, “Spontaneous intestinal perforation due to non-Hodgkin's lymphoma: evaluation of eight cases,” Digestive Diseases and Sciences, vol. 52, no. 8, pp. 1752–1756, 2007.
[95]
T. Yokota, Y. Yamada, Y. Murakami et al., “Abdominal crisis caused by perforation of ileal lymphoma,” American Journal of Emergency Medicine, vol. 20, no. 2, pp. 136–137, 2002.
[96]
D. Hoefer, H. Bonatti, G. Poelzl, W. Mark, H. Ott, and H. Antretter, “Cecal perforation as a rare initial manifestation of post-transplant lymphoproliferative disorder after cardiac transplantation,” The Journal of Heart and Lung Transplantation, vol. 24, no. 4, pp. 505–506, 2005.
[97]
E. Kutsch, P. Kreiger, D. Consolini, and K. N. Furuya, “Colonic perforation after rituximab treatment for post-transplant lymphoproliferative disorder (PTLD),” Journal of Pediatric Gastroenterology and Nutrition, vol. 56, no. 6, p. e41, 2013.
[98]
A. Cornejo, M. Bohnenblust, C. Harris, and G. A. Abrahamian, “Intestinal perforation associated with rituximab therapy for post-transplant lymphoproliferative disorder after liver transplantation,” Cancer Chemotherapy and Pharmacology, vol. 64, no. 4, pp. 857–860, 2009.
[99]
Y.-C. Hsu, W.-C. Liao, H.-P. Wang, M. Yao, and J.-T. Lin, “Catastrophic gastrointestinal manifestations of post-transplant lymphoproliferative disorder,” Digestive and Liver Disease, vol. 41, no. 3, pp. 238–241, 2009.
[100]
“Rituximab: first report of intestinal perforations in an elderly patient: case report,” Reactions, vol. 1, no. 901, pp. 14–15, 2002.
Health Canada, “Reports of bowel obstruction and gastrointestinal perforations with Rituxan,” Rituximab, November 2006, http://www.hc-sc.gc.ca/.
[103]
J. J. Ifthikharuddin, L. A. Mieles, J. D. Rosenblatt, C. K. Ryan, and D. M. Sahasrabudhe, “CD-20 expression in post-transplant lymphoproliferative disorders: treatment with rituximab,” American Journal of Hematology, vol. 65, no. 2, pp. 171–173, 2000.
[104]
V. Leblond, N. Dhedin, M.-F. M. Bruneel et al., “Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders,” Journal of Clinical Oncology, vol. 19, no. 3, pp. 772–778, 2001.
[105]
A. D. Kirk, W. S. Cherikh, M. Ring et al., “Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab,” American Journal of Transplantation, vol. 7, no. 11, pp. 2619–2625, 2007.
[106]
H. Khedmat and S. Taheri, “Heart allograft involvement by posttransplant lymphoproliferative disorders: report from the PTLD. Int survey,” Experimental and Clinical Transplantation, vol. 9, no. 4, pp. 258–264, 2011.
[107]
M. D. Pescovitz, “The use of rituximab, anti-CD20 monoclonal antibody, in pediatric transplantation,” Pediatric Transplantation, vol. 8, no. 1, pp. 9–21, 2004.
[108]
V. Ganne, N. Siddiqi, B. Kamaplath et al., “Humanized anti-CD20 monoclonal antibody (Rituximab) treatment for post-transplant lymphoproliferative disorder,” Clinical Transplantation, vol. 17, no. 5, pp. 417–422, 2003.
[109]
H. S. Kulkarni and P. M. Kasi, “Rituximab and cytokine release syndrome,” Case Reports in Oncology, vol. 5, pp. 134–140, 2012.
[110]
G. Seifert, T. Reindl, S. Lobitz, K. Seeger, and G. Henze, “Fatal course after administration of rituximab in a boy with relapsed all: a case report and review of literature,” Haematologica, vol. 91, no. 6, supplement, p. ECR23, 2006.
[111]
J. C. Byrd, J. K. Waselenko, T. J. Maneatis et al., “Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance,” Journal of Clinical Oncology, vol. 17, no. 3, pp. 791–795, 1999.
[112]
S.-J. Wu, W.-C. Chou, B.-S. Ko, and H.-F. Tien, “Severe pulmonary complications after initial treatment with rituximab for the Asian-variant of intravascular lymphoma,” Haematologica, vol. 92, no. 1, pp. 141–142, 2007.
[113]
P. M. Millward, N. Bandarenko, P. P. Chang et al., “Cardiogenic shock complicates successful treatment of refractory thrombotic thrombocytopenia purpura with rituximab,” Transfusion, vol. 45, no. 9, pp. 1481–1486, 2005.
[114]
A. Arai, A. Nogami, K. Imadome, et al., “Sequential monitoring of serum IL-6, TNF-a, and IFN-c levels in a CAEBV patient treated by plasma exchange and immunochemotherapy,” International Journal of Hematology, vol. 96, no. 5, pp. 669–673, 2012.
[115]
P. Patel, V. Nandwani, J. Vanchiere, S. A. Conrad, and L. K. Scott, “Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A-An associated respiratory failure and hemodynamic shock,” Pediatric Critical Care Medicine, vol. 12, no. 2, pp. e87–e89, 2011.
