Saudi Journal of Kidney Diseases and Transplantation

BRIEF COMMUNICATION
Year
: 2014  |  Volume : 25  |  Issue : 3  |  Page : 597--604

Colorectal involvement by post-transplant lymphoproliferative disorders: A review of 81 cases


Hossein Khedmat, Mohsen Amini, Mohammad Ebrahim Ghamar-Chehreh 
 Baqiyatalah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran

Correspondence Address:
Dr. Mohsen Amini
Baqiyatalah Research Center for Gastro-enterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran
Iran

Abstract

The reported number of patients representing post-transplant lymphoproliferative disorders (PTLD) within the colorectal region is quite limited. In this study, we sought to analyze and compare the characteristics, predictors and prognosis of colorectal localization of PTLDs arising in transplant recipients. A comprehensive search was performed through Pubmed and Google scholar to find case reports and series of colorectal localization of PTLD. Data of each individual patient from different studies were entered into a database and analyzed. Colorectal PTLD was significantly more prevalent in male patients (19.3% vs. 8.5%, respectively; P = 0.002) and represented a significantly shorter time to diagnosis than other localizations (P = 0.044). Multi-organ involvement (75% vs. 46%, respectively; P < 0.001) and disseminated disease (43% vs. 26%, respectively; P = 0.014) were more frequently observed in the colorectal PTLD. There was no survival difference between the two groups. Organ recipients representing colorectal involvement by PTLD are significantly at higher risk for metastasis, especially in their small intestine. Moreover, patients who underwent surgical intervention had low mortality, and, accordingly, we suggest using surgery to manage colorectal PTLD when it is applicable. Prospective studies with larger patient populations are needed to confirm these results.



How to cite this article:
Khedmat H, Amini M, Ghamar-Chehreh ME. Colorectal involvement by post-transplant lymphoproliferative disorders: A review of 81 cases.Saudi J Kidney Dis Transpl 2014;25:597-604


How to cite this URL:
Khedmat H, Amini M, Ghamar-Chehreh ME. Colorectal involvement by post-transplant lymphoproliferative disorders: A review of 81 cases. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Nov 26 ];25:597-604
Available from: https://www.sjkdt.org/text.asp?2014/25/3/597/132201


Full Text

 Introduction



Post-transplant lymphoproliferative disorders (PTLD) represent a major challenging diagnostic and therapeutic dilemma in organ transplant patients. Several authors from all over the world have reported their experience with the PTLD, indicating a high incidence of the disease among recipients of all types of organs. [1] The use of highly potent immunosuppression and viral infections, most notably Epstein-Barr virus (EBV), are the major predisposing factors in the development of the PTLD. [2],[3],[4]

Investigators have suggested that the incidence, time interval, prognosis and presentation of PTLD vary and depend on age of patients, viral infections, immunosuppression intensity, antigen expression and the transplanted organ. [5],[6],[7],[8] The incidence of PTLD has been reported to range from 1-20% in the different populations. [9],[10],[11],[12]

PTLD encompasses a spectrum of clinical manifestations in addition to a wide range of histopathologic findings from B-cell hyperplasia to lymphoma. Lesions primarily occur in the gastrointestinal tract, central nervous system, transplanted organ and, less commonly, lymph nodes. [11],[12] However, the reported number of patients representing PTLD within the colorectal region is quite limited and only a small number of cases with histologically proven PTLD arising in the colon and rectum have been previously reported. Because of the limited number of reports on the issue, data scarcity exists on various aspects of colorectal PTLD occurring in transplant recipients.

We aim in this study to analyze the studies and reports from the medical literature and compare the characteristics, predictors and prognosis of colorectal localization of PTLDs arising in allograft recipients.

 Patients and Methods



We conducted a comprehensive search for the available data by Pubmed and Google scholar for reports of lymphoproliferative disorders occurring in organ transplant patients within their colorectal region. We searched inside the full text of the articles available in the English medical literature and used keywords including "lymphoproliferative disorders + transplantation + colon," "lymphoproliferative disorders + transplantation + rectum," "lymphoproliferative disorder + transplantation + colorectal," "lymphoproliferative disorder + transplantation + sigmoid," "lymphoproliferative disorder + transplantation + caecum," "PTLD + colon," "PTLD + rectum" and "PTLD + caecum." In cases where we were not able to achieve the full text of the articles, e-mails were sent to the correspondent authors requesting the articles. Then, we only included studies in which data of each patient was presented separately and excluded the others.

Lymphoproliferative disorders occurring after transplantation within the colon and rectum were considered as our case group and other transplant patients developing PTLD in other sites were used as controls. A standard questionnaire was developed to collect data from the different published studies. Finally, data from 55 published reports [12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63],[64],[65],[66] were included in the analysis. The time between transplantation and PTLD onset was defined as the period between the graft and the first signs of PTLD or diagnosis. If the PTLD lesion developed before the end of the first year post-transplantation, then the PTLD was considered "early onset," otherwise it was considered as "late onset" PTLD.

Overall, there were 563 recipients of allografts who developed PTLD through their treatment course; of them, 81 (14.4%) patients had colorectal localization of PTLD.

The PTLD patients' status regarding EBV infection was defined according to the results of the serological or polymerase chain reaction (PCR) assays, and it was documented in 429 (76.2%) PTLD patients, of whom 328 (76.5%) were reported positive.

At diagnosis of lymphoma, all patients were receiving immunosuppressive regimens consisting of varying combinations of azathioprine, prednisone, cyclosporine, mycophenolate mofetil and antithymocyte/lymphocyte globulin (ATG/ALG), OKT3, tacrolimus, mTOR inhibitors and alemtuzumab. Very close approach was used to manage the PTLD patients in the included reports; the first step in almost all reports was to decrease or discontinue immunosuppressive therapy, and different regimens of chemotherapy with or without surgical interventions were also used in some of patients.

Response to treatment was defined as any favorable change in the cancer measures as well as patients' clinical condition; data of PTLD on treatment were reported by authors for 186 (33%) patients, of whom 130 (69.9%) responded to therapy. A remission episode was defined as patients being alive after their 24 th month of PTLD diagnosis (as all reported cases having this criterion had at least one confirmed remission episode) and no remission was defined as patients dying within the first month post-PTLD diagnosis (because among reported cases there were no patients who died at the first post-transplant month and reported to have any remission episodes). According to these criteria, 281 (50%) patients had data on remission, of whom 187 (66.5%) had at least one response to treatment, irrespective of their future disease behavior. Overall mortality was 201 patients (53.7% of the reported cases; 189 patients had missing data); death due to PTLD was defined when (1) authors stated it or (2) patient died within six months post-diagnosis unless the authors stated other causes for death, (3) patients died due to PTLD treatment complications. Overall, 127 (63.2% of the whole mortality rate) patients died due to the disease based on the above-mentioned criteria.

 Statistical Analysis



We used SPSS v.13.0 software for data analyses. Statistical differences between patients' subgroups were performed by using the χ[2] and Fishers' exact tests for proportions and the Student's "t" test for continuous parameters. Survival analysis was performed with life tables and Kaplan-Meier methods and log-rank test. We considered P <0.05 as the level of significance for this study.

 Results



Overall, 563 patients with PTLD after organ transplantation were entered into analysis. There were 264 (60%) male and 176 (40%) female patient (123 missing data). Mean age at diagnosis of PTLD was 32.8 ± 21.5 years. The mean interval between transplantation and the diagnosis of PTLD was 48.7 ± 49.8 months, whereas the follow-up time after diagnosis of PTLD was 26.7 ± 35.2 months.

Characteristics of the patients regarding their malignancy site are summarized in [Table 1]. Chi square test showed that male transplant patients were significantly more likely to develop colorectal PTLD than their female counterparts (19.3% vs. 8.5%, respectively; P = 0.002). Moreover, they had a significantly shorter time from transplantation to diagnosis than other sites of the disease (P = 0.044). Transplant recipients with colorectal PTLD were comparable to their counterparts with other PTLD groups in their age at transplantation (P = 0.655), lymphoma cell types (P = 0.438), lymphoma presentation time from transplantation (P = 0.35), EBV positive rate (P = 1.0), overall mortality rate (P = 0.242), death due to the PTLD (P = 1.0) and histopathological features of the PTLD lesions (P = 0.238). {Table 1}

Multi-organ involvement was significantly more prevalent in patients with colorectal PTLD than the other groups (75% vs. 46%, respectively; P <0.001). Disseminated PTLD was also more frequently seen in the colorectal PTLD than in the other groups (43% vs. 26%, respectively; P = 0.014). [Table 2] summarizes the different organ involvements by PTLD when they concomitantly complicate the colon and rectum.{Table 2}

The log-rank test did not show any difference between the colorectal PTLD from the other groups in survival (P = 0.853) [Figure 1]; however, when death only due to PTLD was used as the outcome, a trend toward better outcome was seen for the colorectal PTLD group compared with the other sites (P = 0.602). The 1- and 5-year survival rates for colorectal PTLD patients were 62% and 42%, respectively, while they were 58% and 37%, respectively, for the control group.{Figure 1}

 Discussion



We found in this study no specificity for PTLD lesion arising in colorectal regions compared with those developing in other organs regarding histopathological morphology, EBV infection rate and age of the patients, but it was more likely to develop in the male gender. Moreover, patients who received induction immunotherapy were significantly less likely to develop colorectal PTLD. On the other hand, behavior of the disease was very different regarding PTLD sites; the current analysis of the literature showed that colorectal site of the PTLD is associated with a significantly higher rate of multi-organ and disseminated disease. Moreover, colorectal lesions were diagnosed significantly earlier than other disease sites, suggesting a more aggressive and progressive behavior for this disease location. Analysis of different organs simultaneously involved by the disease also showed that the small intestine is significantly more likely to develop in patients who already have colorectal disease. These findings are highly relevant as they necessitate a more cautious approach in any transplant patient with colorectal PTLD for a potential small bowel metastasis.

None of the treatment strategies for the colorectal PTLD resulted in any outcome advantage, although this finding should be interpreted very cautiously. Having a nonfavorable out-come for patients who had undergone one therapy does not essentially show that it has minimal or no favorable effect on patients' outcome, as the investigators applied different protocols in an uncontrolled fashion. However, finding a more favorable outcome for patients who had undergone surgical intervention represented 33% mortality, rendering it the management of choice when applicable.

Several criticisms may arise over our study as it included patients from different reports and different centers. This fact may make one assume that comparing data of these patients can be associated with bias. We believe that our standardization has effectively made data of our study comparable. Moreover, in some types of data, including metastasis and demographics, center-effect is quite out of view.

In conclusion, this study found that PTLD organ recipients presenting with colorectal involvement are significantly at risk for multi-organ disease and metastasis, especially in their small intestine. Patients who underwent surgical intervention had a low mortality rate. Therefore, we suggest using surgery to manage colorectal sites of PTLD, when it is applicable. Prospective studies with larger patient populations are needed to confirm our results.

Conflict of interest: None

References

1Penn I, Hammond W, Brettschneider L, Starzl TE. Malignant lymphomas in transplantation patients. Transplant Proc 1969;1:106-12.
2Malatack JF, Gartner JC Jr, Urbach AH, Zitelli BJ. Orthotopic liver transplantation, Epstein-Barr virus, cyclosporine, and lymphoproliferative disease: A growing concern. J Pediatr 1991;118: 667-75.
3Pourfarziani V, Taheri S, Lessan-Pezeshki M, et al. Lymphoma after living donor kidney transplantation: An Iranian multicenter experience. Int Urol Nephrol 2008;40:1089-94.
4Cox KL, Lawrence-Miyasaki LS, Garcia-Kennedy R, et al. An increased incidence of Epstein-Barr virus infection and lymphoproliferative disorder in young children on FK506 after liver transplantation. Transplantation 1995; 59:524-9.
5Khedmat H, Taheri S. CD20 Antigen Expression by Lymphoproliferative Disorders after Kidney Transplant is Independently Associated with a Poor Outcome: PTLD.Int Survey. Exp Clin Transplant 2012;10:325-31.
6Izadi M, Taheri S. Allograft involvement by lymphoproliferative disorders after lung transplantation: Report from the PTLD. Int survey. Prog Transplant 2011;21:353-9.
7Khedmat H, Taheri S. Hepatitis C virus infection can affect lymphoproliferative disorders only as a cofactor for Epstein-Barr virus in liver transplant recipients: PTLD.Int survey. Exp Clin Transplant 2012;10:141-7.
8Khedmat H, Taheri S. Heart allograft involvement by posttransplant lymphoproliferative disorders: Report from the PTLD. Int survey. Exp Clin Transplant 2011;9:258-64.
9Swerdlow SH. Classification of the posttransplant lymphoproliferative disorders: From the past to the present. Semin Diagn Pathol 1997; 14:2-7.
10Montone KT, Litzky LA, Wurster A, et al. Analysis of Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after lung transplantation. Surgery 1996;119:544-51.
11Basgoz N, Preiksaitis JK. Post-transplant lymphoproliferative disorder. Infect Dis Clin North Am 1995;9:901-23.
12Loevner LA, Karpati RL, Kumar P, Yousem DM, Hsu W, Montone KT. Posttransplantation lymphoproliferative disorder of the head and neck: Imaging features in seven adults. Radiology 2000;216:363-9.
13Ramalingam P, Rybicki L, Smith MD, et al. Post-transplant lymphoproliferative disorders in lung transplant patients: The Cleveland Clinic experience. Mod Pathol 2002;15:647-56.
14Selinger CP, Howarth G, Willert RP. An unusual inflammation of the colon. Post-transplant lymphoproliferative disorder (PTLD) and diffuse large B cell lymphoma. Gut 2010; 59:1393, 1427.
15Boscà-Robledo A, Pous-Serrano S, García-Mayor RL, Trilles-Olaso LM. Acute abdomen as the first manifestation of a post-transplant lymphoproliferative disorder. Int J Colorectal Dis 2011;26:1081-2.
16Godt C, Regnery A, Schwarze B, Junker K, Porschen R. A rare cause of ulcerative colitis - diarrhoea and perianal bleeding due to post-transplant lymphoproliferative disorder (PTLD). Z Gastroenterol 2009;47:283-7.
17Harada H, Miura M, Shimoda N, et al. A case of plasmacytic hyperplasia arising in a kidney allograft salvaged with immunosuppression reduction alone. Clin Transplant 2004;18 Suppl 11:50-3.
18van Ginkel MW, Diepstra A, Dijkstra G, Nieuwenhuijs VB, de Langen ZJ, Rings EH. Endoscopic detection of an early manifestation of EBV-related post-transplant lymphoproliferative disorder in a transplanted colon. Endoscopy 2010;42 Suppl 2:E101-2.
19Medlicott SA, Devlin S, Helmersen DS, Yilmaz A, Mansoor A. Early post-transplant smooth muscle neoplasia of the colon presenting as diminutive polyps: A case complicating post-transplant lymphoproliferative disorder. Int J Surg Pathol 2006;14:155-61.
20Kim MJ, Yun SH, Chun HK, Lee WY, Cho YB. Post-transplant lymphoproliferative disorder localized in the colon after liver transplantation: Report of a case. Surg Today 2009;39:1076-9.
21Chen 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;131:632-9.
22Levine SM, Angel L, Anzueto A, et al. A low incidence of posttransplant lymphoproliferative disorder in 109 lung transplant recipients. Chest 1999;116:1273-7.
23McGhee W, Mazariegos GV, Sindhi R, Abu-Elmagd K, Reyes J. Rituximab in the treatment of pediatric small bowel transplant patients with posttransplant lymphoproliferative disorder unresponsive to standard treatment. Transplant Proc 2002;34:955-6.
24Berg LC, Copenhaver CM, Morrison VA, et al. B-cell lymphoproliferative disorders in solid-organ transplant patients: Detection of Epstein-Barr virus by in situ hybridization. Hum Pathol 1992;23:159-63.
25Nozu K, Iijima K, Fujisawa M, Nakagawa A, Yoshikawa N, Matsuo M. Rituximab treatment for posttransplant lymphoproliferative disorder (PTLD) induces complete remission of recurent nephrotic syndrome. Pediatr Nephrol 2005;20: 1660-3.
26Orjuela M, Gross TG, Cheung YK, Alobeid B, Morris E, Cairo MS. A pilot study of chemo-immunotherapy (cyclophosphamide, prednisone, and rituximab) in patients with post-transplant lymphoproliferative disorder following solid organ transplantation. Clin Cancer Res 2003;9: 3945-52S.
27O'Conner AR, Franc BL. FDG PET imaging in the evaluation of posttransplant lymphoproliferative disorder following renal transplantation. Nucl Med Commun 2005;12:1107-11.
28Gallagher H, Kwan JT, Andrews PA. Post-transplantation lymphoproliferative disorder: An unusual presentation in a patient receiving tacrolimus. Nephrol Dial Transplant 2000;15: 928-30.
29Muzaffar M, Taj A, Ratnam S. Aggressive post-transplant lymphoproliferative disease in a renal transplant patient treated with alemtuzumab. Am J Ther 2010;17:e230-3.
30Kim MJ, Yun SH, Chun HK, Lee WY, Cho YB. Post-transplant lymphoproliferative disorder localized in the colon after liver transplantation: Report of a case. Surg Today 2009;39:1076-9.
31Luo Y, Zhang AB, Huang H, Zheng SS. Is hepatitis B virus reactivation a risk factor in the development of posttransplant lymphoproliferative disorder following liver transplantation? Chin Med J (Engl) 2008;121:1237-40.
32McCormack L, Hany TI, Hübner M, et al. How useful is PET/CT imaging in the management of post-transplant lymphoproliferative disease after liver transplantation? Am J Transplant 2006;6:1731-6.
33Patel H, Vogl DT, Aqui N, et al. Posttransplant lymphoproliferative disorder in adult liver transplant recipients: A report of seventeen cases. Leuk Lymphoma 2007;48:885-91.
34Dhillon MS, Rai JK, Gunson BK, Olliff S, Olliff J. Post-transplant lymphoproliferative disease in liver transplantation. Br J Radiol 2007;80:337-46.
35Burra P, Buda A, Livi U, et al. Occurrence of post-transplant lymphoproliferative disorders among over thousand adult recipients: Any role for hepatitis C infection? Eur J Gastroenterol Hepatol 2006;18:1065-70.
36Peterson MR, Emery SC, Yung GL, Masliah E, Yi ES. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder following lung transplantation is more commonly of host origin. Arch Pathol Lab Med 2006;130: 176-80.
37Wood BL, Sabath D, Broudy VC, Raghu G. The recipient origin of posttransplant lymphoproliferative disorders in pulmonary transplant patients. A report of three cases. Cancer 1996; 78:2223-8.
38Abe T, Ichimaru N, Kokado Y, et al. Post-transplant lymphoproliferative disorder following renal transplantation: A single-center experience over 40 years. Int J Urol 2010;17:48-54.
39Sarkar S, Selvaggi G, Mittal N, et al. Gastro-intestinal tract ulcers in pediatric intestinal transplantation patients: Etiology and management. Pediatr Transplant 2006;10:162-7.
40Mucha K, Foroncewicz B, Niemczyk K, et al. Tonsil enlargement after liver transplantation in adults--reason enough for tonsillectomy? Two cases of tonsillar posttransplantation lymphoproliferative disease. Liver Transpl 2007;13: 918-23.
41Manlhiot C, Pollock-Barziv SM, Holmes C, et aI. Post-transplant lymphoproliferative disorder in pediatric heart transplant recipients. J Heart Lung Transplant 2010;29:648-57.
42Craig FE, Gulley ML, Banks PM. Posttransplantation lymphoproliferative disorders. Am J Clin Pathol 1993;99:265-76.
43Cacciarelli TV, Green M, Jaffe R, et al. Management of posttransplant lymphoproliferative disease in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy. Transplantation 1998;66:1047-52.
44Allen UD, Farkas G, Hebert D, et al. Risk factors for post-transplant lymphoproliferative disorder in pediatric patients: A case- control study. Pediatr Transplant 2005;9:450-5.
45Dusenbery D, Nalesnik MA, Locker J, Swerdlow SH. Cytologic features of post-transplant lymphoproliferative disorder. Diagn Cytopathol 1997;16:489-96.
46Hézode C, Duvoux C, Germanidis G, et al. Role of hepatitis C virus in lymphoproliferative disorders after liver transplantation. Hepatology 1999;30:775-8.
47Lones MA, Kirov I, Said JW, Shintaku IP, Neudorf S. Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient. Bone Marrow Transplant 2000;26:1021-4.
48Issa N, Amer H, Dean PG, et al. Posttransplant lymphoproliferative disorder following pancreas transplantation. Am J Transplant 2009;9:1894-902.
49Bakker NA, Van Imhoff GW, Verschuuren EA, et al. Early onset post-transplant lymphoproliferative disease is associated with allograft localization. Clin Transplant 2005;19:327-34.
50Randhawa PS, Magnon M, Joradan M, Shapiro R, Demetris AJ, Nalesnik M. Renal allograft involvement by Epstein-Barr virus associated post-transplant lymphoproliferative disease. Am J Surg Pathol 1996;20:563-71.
51Shitrit D, Shitrit AB, Dickman R, Sahar G, Saute M, Kramer MR. Gastrointestinal involvement of posttransplant lymphoproliferative disorder in lung transplant recipients: Report of a case. Dis Colon Rectum 2005;48:2144-7.
52Norin S, Kimby E, Ericzon BG, et al. Post-transplant lymphoma--a single-center experience of 500 liver transplantations. Med Oncol 2004; 21:273-84.
53Vakiani E, Basso K, Klein U, et al. Genetic and phenotypic analysis of B-cell post-transplant lymphoproliferative disorders provides insights into disease biology. Hematol Oncol 2008;26: 199-211.
54Chen PL, Chang HH, Chen IM, et al. Malignancy after heart transplantation. J Chin Med Assoc 2009;72:588-93.
55Wilde GE, Moore DJ, Bellah RD. Posttransplantation lymphoproliferative disorder in pediatric recipients of solid organ transplants: Timing and location of disease. AJR Am J Roentgenol 2005;185:1335-41.
56Trappe R, Riess H, Babel N. Salvage chemotherapy for refractory and relapsed Posttransplant Lymphoproliferative Disorders (PTLD) After Treatment With Single-Agent Rituximab. Transplantation 2007;83:912-8.
57Lucioni M, Ippoliti G, Campana C, et al. EBV positive primary cutaneous CD30+ large T-cell lymphoma in a heart transplanted patient: Case report. Am J Transplant 2004;4:1915-20.
58Jain A, Nalesnik M, Reyes J, et al. Post-transplant lymphoproliferative disorders in liver transplantation: A 20-year experience. Ann Surg 2002;236:429-36.
59Paraskevas S, Coad JE, Gruessner A, et al. Posttransplant lymphoproliferative disorder in pancreas transplantation: A single-center experience. Transplantation 2005;80:613-22.
60Hachem RR, Chakinala MM, Yusen RD, et al. Abdominal-pelvic lymphoproliferative disease after lung transplantation: Presentation and outcome. Transplantation. 2004;77:431-7.
61Duvoux C, Pageaux GP, Vanlemmens C, et al. Risk factors for lymphoproliferative disorders after liver transplantation in adults: An analysis or 480 patients. Transplantation 2002;74:1103-9.
62Dotti G, Fiocchi R, Motta T, et al. Lymphoma occurring late after solid organ transplantation: Influence of treatment on the clinical outcome. Transplantation 2002;74:1095-102.
63Schaar CG, van der Pijl JW, van Hoek B, et al. Successful outcome with a quintuple approach of posttransplant lymphoproliferative disorders. Transplantation 2001;71:47-52.
64Hanto DW, Frizzera C, Purtilo DT, et al. Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. Cancer Res 1981;41:4253-61.
65Koike J, Yamaguchi Y, Hoshikawa M, et al. Post-transplant lymphoproliferative disorders in kidney transplantation: Histological and molecular genetic assessment. Clin Transplant 2002; 16 Suppl 8:12-7.
66Mamzer-Bruneel MF, Lome C, Morelon E, et al. Durable remission after aggressive chemotherapy for very late post-kidney transplant lymphoproliferation: A report of 16 cases observed in a single center. J Clin Oncol 2000; 18:3622-32.