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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 19  |  Issue : 1  |  Page : 61-62

A case of posttransplant lymphoproliferative disorder


1 Department of Medicine, INHS Asvini, Mumbai, Maharashtra, India
2 Department of Pathology, INHS Asvini, Mumbai, Maharashtra, India

Date of Web Publication17-Aug-2017

Correspondence Address:
Dr Malav Darshan Jhala
206, B Wing, Serenity Heights, Off Link Road, Malad West, Mumbai - 400 064, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmms.jmms_13_17

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  Abstract 


Posttransplant lymphoproliferative disorders (PTLDs) are life-threatening complications of solid-organ and bone marrow transplantations leading to a high mortality. PTLD represents a heterogeneous group of lymphoproliferative diseases. They become clinically relevant because of the expansion of transplantation medicine together with the development of potent immunosuppressive drugs associated now with a long survival. The risk of PTLD is highest in the early posttransplant period, but the cumulative risk increases with time. We report a case of two sequential malignancies – carcinoma bladder - 13 years and now gastric lymphoma - 15 years after renal transplantation in a 73-year-old male.

Keywords: Carcinoma bladder, gastric lymphoma, posttransplant


How to cite this article:
Chowdhary G S, Jhala MD, Kaur G. A case of posttransplant lymphoproliferative disorder. J Mar Med Soc 2017;19:61-2

How to cite this URL:
Chowdhary G S, Jhala MD, Kaur G. A case of posttransplant lymphoproliferative disorder. J Mar Med Soc [serial online] 2017 [cited 2020 Jul 11];19:61-2. Available from: http://www.marinemedicalsociety.in/text.asp?2017/19/1/61/213093




  Introduction Top


The term “posttransplant lymphoproliferative disorder” or disease (PTLD) was first introduced in 1984 by Starzl et al.[1] Today, it represents a heterogeneous group of lymphoproliferative diseases, ranging from Epstein–Barr virus (EBV)-associated polyclonal proliferation to highly aggressive monomorphic proliferations, such as diffuse large B-cell lymphoma.[2],[3] The reported incidence of PTLD is very variable due to its related mortality (30%–60%). The clinical picture, intensity of immunosuppression, primary and co-existing diseases, and PTLD location are also quite variable.


  Case Report Top


A 73-year-old male on immunosuppressive therapy was admitted to hospital with longstanding gaseous dyspepsia and pain abdomen. Amend the statement: He was a case of end-stage renal disease due to recurrent pyelonephritis and had received a cadaveric renal transplant in January 1999. His induction immunosuppression had been antithymocyte serum, and he had been maintained on azathioprine, cyclosporine, and prednisone. A transplant kidney biopsy in 2003 for worsening creatinine showed only 10% interstitial fibrosis without acute rejection. He was also being maintained on low-dose immunosuppression because of residual renal function from the transplanted kidney.

Laboratory data on admission showed new anemia with elevated serum lactate dehydrogenase (LDH). Cultures of blood and urine were sterile. Integrated positron emission tomography-computed tomography imaging showed thickening of the gastric mucosa to 13 mm with standardized uptake value of 17.5 along with fluorodeoxyglucose avid perigastric and gastrosplenic nodes. Upper gastrointestinal endoscopy revealed a large gastric ulcer in the body of stomach extending up to the greater curvature. An endoscopic biopsy confirmed high-grade non-Hodgkin lymphoma (NHL) (DLBC type). On immunohistochemistry, leukocyte common antigen and CD20 were positive with AE1/AE3 negative. The lymphomatous gastric ulcer was also involved with Candida. Bone marrow aspirate and biopsy revealed 40% cellularity and excluded lymphomatous involvement in bone marrow. He was staged to Stage IIA extranodal NHL and was treated with R-CHOP regimen (rituximab, cyclophosphamide, hydroxydaunomycin/doxorubicin, vincristine, and prednisolone) (renal chemotherapy) and antifungal therapy with intravenous anidulafungin. Immunosuppression was continued as per protocol. However, in view of a poor prognosis of this patient and honoring the wish of the family members, aggressive chemotherapy was not pursued and comfort care was administered. The patient eventually succumbed to his illness.


  Discussion Top


Lymphoproliferative malignant disorders are seen in about 10% of patients after solid-organ transplants.

In recipients of renal allograft, PTLD incidence is 1%. T-cell lymphoma accounts for 10%–15% of PTLDs. The incidence of PTLD in various clinical studies varies due to a lack of standardization of inclusion criteria. In a recent multicenter analysis of more than 50,000 kidney and cardiac transplant recipients from North America and Europe, the incidence of NHL was higher during the 1st year after transplantation; however, it declined in the subsequent years.

Heart–lung transplant recipients showed the highest relative risk of 239.5 among other types of solid-organ transplants. The Collaborative Transplant Study database was used to evaluate graft survival and NHL at 3 years according to the type of induction therapy in 112,122 patients receiving a deceased-donor renal graft during 1985–2004. Graft survival was significantly improved with induction using thymoglobulin and interleukin-2 receptor antibody, but there was also an increased risk of lymphoma with the induction therapy using anti-CD3 or antithymocyte globulin.

In a recent study by Kirk et al., data of 60,000 renal recipients were analyzed for a possible relationship between induction agent and PTLD.[4] Antithymocyte globulin was associated with a significantly increased risk for PTLD (P = 0.0025) whereas alemtuzumab (P = 0.74), basiliximab (P = 0.33), and daclizumab showed a trend toward a protective effect (P = 0.06). Patients receiving chronic prednisone and azathioprine treatment are at an increased risk for developing NHL. However, randomized trials did not find any difference in the risk of PTLD development with the use of cyclosporine and tacrolimus. Some registries suggest that the risk of PTLD increases by a factor of 1.5–2 with the use of tacrolimus compared with cyclosporine. EBV-related infection is an important causative factor in the origin of most B-cell-related PTLDs. Although several cases of T-cell lymphoma have been described in EBV-positive patients, the associations are not well established. In a study by Opelz et al., the Collaborative Transplant Study database for known pretransplant EBV and cytomegalovirus serostatus and occurrence of NHL was analyzed. Regardless of age, a pretransplant-negative EBV status was significantly associated with the risk of NHL in kidney transplant recipients (P< 0.001). The risk of PTLD in EBV-negative recipients was increased by a factor of 6. Cytomegalovirus serological status was not independently associated with the risk of NHL after renal transplantation. Most T-cell lymphomas occur several years posttransplantation; very few cases of T-cell PTLD have been reported during the 1st year posttransplantation.[5] Our patient developed T-cell lymphoma 17 years after receiving his renal graft. Our extensive review of literature revealed only one case of T-cell lymphoma occurring as late as ours.[6] The outcome of PTLD is usually poor. Based on the review of various transplant databases, the 1-year mortality has been found to be around 40%–50%. The poor prognostic factors include late onset, older recipient age, high LDH, poor performance status, T-cell PTLD, and multisystem disease. PTLD therapy is still equivocal. Reduction of immunosuppression is helpful in early disease. Surgical removal and radiation therapy are useful only for localized lesions. Cytotoxic therapy as well as antiviral chemotherapy has been reported to be helpful in selected cases. Recently in 2016, The Sixth European Conference on Infections in Leukemia 2015 reviewed the literature on EBV-related PTLD in solid-organ transplants as well as hematopoietic stem cell transplants and has released consensus guidelines to define, diagnose, and manage PTLDs in transplant patients. It has also provided guidelines to screen transplant recipients for possible EBV infection using EBV DNA polymerase chain reaction as well as to initiate preemptive therapy in infected recipients.[7]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1984;1:583-7.  Back to cited text no. 1
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2.
Nalesnik MA. The diverse pathology of post-transplant lymphoproliferative disorders: The importance of a standardized approach. Transpl Infect Dis 2001;3:88-96.  Back to cited text no. 2
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3.
Tanner JE, Alfieri C. The Epstein-Barr virus and post-transplant lymphoproliferative disease: Interplay of immunosuppression, EBV, and the immune system in disease pathogenesis. Transpl Infect Dis 2001;3:60-9.  Back to cited text no. 3
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4.
Kirk AD, Hale DA, Mannon RB, Kleiner DE, Hoffmann SC, Kampen RL, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation 2003;76:120-9.  Back to cited text no. 4
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5.
Werdlow SH, Webber SA, Chadburn A, Campo E, Harris NL, Jaffe ES, et al. Post-transplant lymphoproliferative disorders. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008.  Back to cited text no. 5
    
6.
Ziari M, Kudva GC, Salinas-Madrigal L, Cortese C, Garvin P, Osman MM, et al. Late occurrence of malignant Post-Transplant Lymphoproliferative Disorder (PTLD) presenting with severe acute renal failure. Dial Transplant 2007;36:276-82.  Back to cited text no. 6
    
7.
Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, et al. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica 2016;101:803-11.  Back to cited text no. 7
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