Pure red cell aplasia preceding malignant lymphoma in a renal transplant patient

Malignant disorders are one of the major causes of morbidity and mortality in transplant patients. We present herein a renal transplant recipient with malignant lymphoma which preceded by pure red cell aplasia (PRCA). Acquired PRCA is a rare hematologic disorder in renal transplant recipients. It has been associated with a variety of disorders of immunologic dysfunction and neoplasms, exposure to drugs and toxins, infectious diseases, pregnancy and severe nutritional deficiency. This is the first case with PRCA preceding the malign lymphoma in a renal transplant patient. Treatment of lymphoma and lymphoma-related humoral and cellular changes or other undefined effects that may be related to therapy may be responsible of the resolving of PRCA in this patient. In this regard, renal transplant patients with acquired PRCA, must be closely followed for an underlying neoplastic disorder.     

High-dose busulfan and the risk of pulmonary mortality after autologous stem cell transplant

The non-relapse mortality of autologous stem cell transplant is low enough that the procedure has been extended to older patients with non-Hodgkin's lymphoma. We treated 537 non-Hodgkin's lymphoma patients with high-dose chemotherapy consisting of busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplant. Sixteen patients were identified who died of pulmonary complications at a five-year incidence of 3.6%. Risk factors for pulmonary mortality included older age and lower baseline D(CO) and FEV1. We conclude that high-dose busulfan is associated with pulmonary mortality after autologous transplant, particularly in older patients.     

Will mixed chimerism cure autoimmune diseases after a nonmyeloablative stem cell transplant?

BACKGROUND: Mixed chimerism after allogeneic bone marrow transplantation has been shown to cure a number of genetic disorders in both the clinical and experimental settings. Although encouraging results have been reported from animal experiments, the role of mixed chimerism in eliminating autoimmune disorders is not clear. METHODS: A 50-year-old man with extensive psoriasis received an allogeneic transplant from his brother after nonmyeloablative conditioning with fludarabine, melphalan, and Campath-1H for relapsed non-Hodgkin's lymphoma. The chimerism status and the immunological recovery after the transplant were serially monitored. RESULTS: Twenty-one months after the transplant, the patient continues to be in complete remission from psoriasis and lymphoma with stable mixed chimerism (30% to 40% donor cells), despite significant recovery of T-cell subsets and antigen-specific response. CONCLUSIONS: If mixed chimerism can be achieved safely with novel low-intensity conditioning regimens and results in sustained remission of autoimmune diseases, allogeneic transplantation may become a realistic therapy in the management of some patients with autoimmune disease.     

Bronchogenic carcinoma in lung transplant recipients.

Although lung transplant recipients have a higher prevalence of non-melanoma skin cancers and lymphoma than the general population, the same has not been noted for bronchogenic carcinoma. If an increased prevalence of bronchogenic carcinoma exists, contributing factors may include the high rate of previous tobacco use in this population and/or the chronic immunosuppression used to prevent allograft rejection. With time, the incidence of bronchogenic carcinoma in the lung transplant population is likely to parallel the increasing longevity and number of transplanted individuals. We describe 2 cases of bronchogenic carcinoma in lung transplant recipients that demonstrate the morbidity associated with the discovery or development of bronchogenic carcinoma in this population.     

Cancer after renal transplantation

PURPOSE OF REVIEW: Prolonged waiting times for renal transplantation, an increase in the average age of recipients, decreased acute rejection rates due to use of newer potent immunosuppressives and improving long-term transplant survival have raised concerns in the transplant community regarding posttransplant cancer. In view of the fact that transplant recipients are living longer, it is of paramount importance that we continue to translate discoveries at the bench to the bedside and document cancers in the posttransplant recipient registries. Analysis of data will help in optimizing patient management. RECENT FINDINGS: Recent evidence indicates that sirolimus is associated with a decreased incidence of posttransplant de-novo cancer and remission of Kaposi's sarcoma and nonmelanoma skin cancer. Mycophenolate mofetil has been shown to have an antiproliferative activity against leukemia and lymphoma and an anti-tumor effect against colon and prostate cancer. Clinically it has been shown to be associated with a reduced incidence of cancers like posttransplant lymphoproliferative disorder. SUMMARY: Appropriate selection of transplant candidates, pretransplant and posttransplant cancer surveillance and judicious evidence-based use of newer immunosuppressants may help reduce the incidence and improve the outcome of posttransplant cancer.     

Epstein-Barr virus-negative precursor B cell lymphoblastic lymphoma after liver transplantation: a unique form of posttransplant lymphoproliferative disease

BACKGROUND: We report a liver transplant patient with Epstein-Barr virus-negative, precursor B cell lymphoblastic lymphoma diagnosed 6 months after transplantation. PATIENT: The patient was a 13-year-old boy with acute, fulminant hepatic failure of unknown etiology who underwent cadaveric liver transplantation. RESULTS: Six months after the transplant, the patient developed non-tender cervical lymphadenopathy 2 days after a reduction in prednisone dosage. The adenopathy worsened despite withdrawal of immunosuppression, and a biopsy showed precursor B cell lymphoblastic lymphoma. All investigations for Epstein-Barr virus were negative. The patient responded well to chemotherapy and is currently in complete remission 24 months after diagnosis. CONCLUSIONS: Precursor B cell lymphoblastic lymphoma has not been previously reported as a form of posttransplant lymphoproliferative disease. We discuss this unique form of posttransplant lymphoproliferative disease and briefly review the clinical and pathological spectrum of posttransplant lymphoproliferative disease.     

Primary central nervous system lymphoma in a renal transplant recipient with Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder. End-stage renal failure has been reported as the most frequent cause of death in this disorder. There are few reports of kidney transplantation in these patients. Renal transplant patients are known to be at increased risk for the development of malignancies. Although a few patients with BBS have been described to develop malignant disease, there was no previous association with lymphoma. We report a 20-year-old patient in whom primary central nervous system lymphoma was diagnosed 20 months after renal transplantation.     

Risk of lymphoma after renal transplantation varies with time: an analysis of the United States Renal Data System

BACKGROUND: Characterization of the incidence of posttransplant lymphoma over time may help guide the timing and intensity of posttransplant monitoring. We analyzed the United States Renal Data System to describe the occurrence of lymphoma following renal transplantation. METHODS: All end-stage renal disease patients placed on the transplant waiting list between January 1, 1990 and December 31, 1999 were considered. Survival analysis was used to estimate lymphoma risk in renal transplant patients. RESULTS: Of 89,260 eligible patients, a total of 556 lymphoma cases were identified with 357 in transplant patients. The overall rate of posttransplant lymphoma was 33.3/10,000 person-years in transplant patients. There was variation in the duration and magnitude of increased lymphoma risk by age. The highest rates of lymphoma were among transplanted patients in the first 12 months, after which the rate of lymphoma decreased. Among Caucasian transplant recipients less than 25 years of age, the adjusted relative risk of lymphoma ranged from 13.82 [95% CI: (3.96, 48.15)] within 6 months posttransplant to 3.46 [95% CI: (0.69, 17.44)] within months 30-36 posttransplant. Only patients under 25 years had a notably increased risk beyond the first 2 posttransplant years. The risk of lymphoma differed by race, with Caucasian patients at nearly double the risk of African-Americans. Gender was not associated with lymphoma incidence. CONCLUSIONS: We found and quantified a time-varying relationship between renal transplant and lymphoma risk. This information can be used in combination with knowledge of established risk factors to guide the schedule of posttransplant monitoring.     

Cadaveric renal transplantation in two patients with preexisting Hodgkin's lymphoma

Two young men developed nephrotic syndrome associated with Hodgkin's lymphoma and progressive renal failure. After a short course of hemodialysis with blood transfusion, each received a cadaveric renal transplant. During the postoperative period, chemotherapy (MOPP) was given. No transplant rejection episodes were diagnosed. The patients, who live normal lives, have been in lymphoma remission for 12 and 22 months and have serum creatinine levels of 120 and 108 mumol/L 47 and 50 months posttransplant, respectively (Table 1).     

Nasal natural killer cell lymphoma in a post-renal transplant patient

Posttransplant lymphoproliferative disorders in organ allograft recipients are most commonly of B-cell origin and only occasionally of T-cell origin. We present here a case of nasal natural killer cell lymphoma associated with Epstein-Barr virus that occurred in a recipient of a renal transplant 4 years posttransplantation. Immunohistochemically, the lymphoma cells showed CD2-, surface CD3-, cytoplasmic CD3E+, CD56+, CD57-, CD16-, and CD43+ phenotype. Analyses of T-cell receptor beta and gamma genes showed germ line configurations. EBER-1 was detectable in the lymphoma cells. The patient was diagnosed as having natural killer cell lymphoma and was treated with six courses of combination chemotherapy for non-Hodgkin's lymphoma He has been in remission for more than 3 years thereafter. To the best of our knowledge, this is the first report of a posttransplant NK cell lymphoma associated with Epstein-Barr virus.     

Treatment of post-transplant lymphoproliferative disorder with monoclonal CD20 antibody (rituximab) after heart transplantation.

Post-transplant lymphoproliferative disorder (PTLD) is a frequent and often fatal complication of organ transplantation. It most often results from an Epstein-Barr virus (EBV)-transformed B-cell clone, which expresses B-cell surface markers such as CD20. We describe a case of a heart transplant recipient who EBV seroconverted post-transplant and subsequently developed subcutaneous and lymphatic B-cell lymphoma, successfully treated with CD20 antibody (rituximab). The patient has been in remission during 10 months of clinical follow-up.     

Lymphoma and hypercalcemia in a pediatric orthotopic liver transplant patient

We present a case report of a pediatric orthotopic liver transplant recipient who developed lymphoma with hypercalcemia on cyclosporine and prednisone immunosuppression. This is the first reported posttransplant lymphoproliferative disorder complicated by hypercalcemia, with a finding of an elevated 1,25 dihydroxyl vitamin D state, suggesting that it has a role in the pathophysiology of this B cell lymphoma hypercalcemia. The clinical course and management of this disorder with a 31-month follow-up are described.     

Extracorporeal photochemotherapy for Epstein-Barr virus-associated lymphoma after lung transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication after transplantation of solid organs. Highest incidence rates have been reported for lung transplant recipients. With the current treatment strategy for early onset PTLD, a reduction of immunosuppressive drugs, mortality of lung transplant recipients with PTLD remains high, due to both, incomplete control of PTLD and transplant rejection. We present a lung transplant recipient with a history of acute rejection and Epstein Barr virus-associated posttransplantation malignant non-Hodgkin's lymphoma. Extracorporeal photochemotherapy, in combination with a moderate reduction of immunosuppressive therapy, resulted in complete disappearance of PTLD. After a first year of follow-up, no further rejection and no recurrence of PTLD have occurred. Treatment with ECP, with its beneficial effects on both, rejection after organ transplantation and malignant lymphoma, may be a particularly valuable approach for the treatment of PTLD in patients after lung transplantation, with its increased risk for transplant rejection.     

Pseudolymphoma in renal allograft recipients.

Five renal transplant recipients exhibited giant systemic lymphadenopathy shortly after transplantation. Biopsy specimens did not show Hodgkin's lymphoma. Immunosuppression was continued in all patients. In contrast to the rapidly fatal course of malignant lymphoma in transplant recipients, adenopathy in these five patients has uniformly resolved. Patients have been observed for 6 to 15 months with no evidence of residual disease. Interval biopsy specimens are not malignant. Each patient received antithymocyte globulin from a single lot for 10 to 21 days after transplantation. During administration, T cell lymphocytes were suppressed to 5% of control values. When lymphadenopathy occurred, T cell values rebounded to 371% of control values. Toxoplasmosis titers as well as viral cultures of lymph node biopsy specimens were negative. These data indicate a benign course of this histologically malignant disease and suggest a lymphoblastic rebound phenomenon to antithymocyte globulin.     

A poorly differentiated lymphoma of donor origin in a renal allograft recipient

Malignant lymphoma is a frequent complication of organ transplantation. It has been suggested that such tumors arise as a result of uncontrolled proliferation of Epstein-Barr virus-infected B lymphocytes in an immunosuppressed host. Although a few cases of posttransplant lymphomas in bone marrow transplantation have been shown to be of donor cell origin, no recipients of solid-organ transplants are known to have developed lymphomas arising from donor cells. In this report, a case of diffuse high-grade lymphoma that apparently arose in the allograft of a renal transplant recipient is described. DNA fingerprinting demonstrated the tumor to be of donor origin; Epstein-Barr sequences were absent. A therapeutic trial consisting of withdrawal of immunosuppressive agents and administration of acyclovir was unsuccessful. These data support the notion that donor cells can undergo malignant transformation in solid-organ transplant recipients, and such tumors need not carry EBV genetic material.     

T cell extranodal lymphoma case involving pleura and pericardium in a renal transplant patient

Application of immunosuppressive treatment for a long period after organ transplantations suppresses immune system in organ receivers and increases the risk of development of neoplastic diseases along with infections. Among the complications developing after transplantation, post-transplant lymphoproliferative diseases are not rare. Although the disease is generally of B cell origin, cases of rare post-transplant lymphoproliferative disease of T cell origin have been reported. Post-transplant lymphoproliferative disease often occurs after Epstein-Barr virus (EBV) infection. In our case an extranodal T cell lymphoma originating from the pleura and pericardium in a renal transplant patient has been diagnosed with cytology.     

Spleen-Restricted Posttransplant Lymphoproliferative Disorder in the First Year After Kidney Transplant – A Case Report

Posttransplant lymphoproliferative disorders (PTLDs) are a feared complication after transplant. They are mostly of B cell origin and are frequently Epstein-Barr virus (EBV)–positive, particularly in early onset PTLD. Later on, non-B and EBV-negative PTLD are increasingly reported. EBV seronegative receptors (particularly when paired with an EBV seropositive donor) together with the net degree of immunosuppression—a concept often difficult to quantify—are the most consistently described risk factors for the development of PTLD. Conversely, its association with a particular immunosuppressive agent or other virus, namely cytomegalovirus (CMV) infection or disease, has been inconsistently reported. We present a challenging case where an EBV negative monomorphic peripheric T-cell lymphoma was diagnosed in the first year after kidney transplant in a patient with a recent history of CMV disease from a resistant strain.     

Prospective Registry-Based Observational Cohort Study of the Long-Term Risk of Malignancies in Renal Transplant Patients Treated with Mycophenolate Mofetil

This large prospectively conducted observational cohort study examined the risk of lymphoma and other malignancies with mycophenolate mofetil (MMF) in de novo renal transplant recipients. A total of 6751 patients receiving MMF, and an equal number of matched controls receiving non-MMF-based immunosuppression, were identified from two large registries (Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) and Collaborative Transplant Study (CTS)) and followed for 3 years. The primary endpoint was development of lymphoma. Secondary endpoints included development of any malignancy. There was no evidence of any increased risk of developing lymphoma or malignancy with MMF. The risk of developing lymphoma with MMF compared with the non-MMF cohort was not higher in either the CTS registry (relative risk (95% confidence interval); 0.4 (0.17-0.94)) or the OPTN/UNOS registry (1.04 (0.61-1.78)). In the MMF group, there was a trend toward a lower risk of malignancy in both registries (OPTN/UNOS 0.86 (0.69-1.07); CTS 0.79 (0.61-1.02)) and a significant increase in time to malignancy in the CTS dataset (p < 0.026). This study has demonstrated that MMF is not associated with an increased risk of lymphoma or other malignancies post-renal transplant, and may even be associated with a lower risk in some populations.     

Helicobacter pylori-associated gastric MALT lymphoma in liver transplant recipients

BACKGROUND: Immunosuppressed transplant recipients are at increased risk of developing several forms of malignancy. The aim of this study is to report the clinical presentation, treatment, and outcome of four liver transplant recipients with Helicobacter pylori-associated gastric mucosae-associated lymphoid tissue (MALT) lymphoma. METHODS: The medical records of four liver transplant recipients with gastric MALT lymphoma were reviewed. In situ hybridization for Epstein-Barr-encoded ribonucleic acid was performed on formalin-fixed tissues. RESULTS: All four subjects presented with abdominal symptoms at a mean of 6.1 years posttransplant. Ulcerative lesions biopsied at endoscopy demonstrated early-stage gastric MALT lymphoma with associated Helicobacter pylori gastritis. In situ hybridization revealed no evidence of Epstein-Barr virus infection in examined tissues. Antibiotic eradication of Helicobacter pylori lead to disease remission in three subjects with a mean follow-up of 21 months, and one subject failed to respond to antibiotics and radiation therapy and died from metastatic gastric adenocarcinoma. CONCLUSIONS: Early-stage, low-grade gastric MALT lymphoma that was associated with Helicobacter pylori gastritis responded to antibiotic therapy with a sustained clinical remission in three of four treated subjects. If other studies confirm a higher than expected incidence of gastric MALT lymphoma in immunosuppressed transplant recipients with Helicobacter pylori infection, screening and treating Helicobacter pylori infection in selected transplant patients may prove beneficial.     

Anaplastic large cell lymphoma associated with Epstein-Barr virus following cardiac transplant

Posttransplantation lymphoproliferative disorders (PTLDs) eventually occur in approximately 5% of all organ transplant recipients. Most of cases are B-cell proliferations associated with the Epstein-Barr virus (EBV). T-cell PTLDs are relatively rare, although some estimate that up to 14% of posttransplantation malignant lymphomas are T-cell lymphomas even though only a few of these cases are described in the literature. A literature review found only 77 cases of T-cell PTLD, including 1 case following cardiac transplant, 15 cases associated with EBV, and only 1 case of anaplastic large cell lymphoma (ALCL). This single ALCL case followed a liver transplant, was of the T-cell phenotype, and was EBV negative. In this report, we describe a 14-year-old male who developed an EBV-positive, T-cell PTLD of the ALCL subtype after a period of 14 years following cardiac transplant. Immunohistochemical staining established the T-cell origin of the neoplasm with strong expression of CD45, CD3, CD43, and CD2 and also showed expression of CD30 consistent with the histologic features that suggested ALCL. EBER in situ hybridization detected the presence of the EBV. Polymerase chain reaction analysis for T-cell receptor-gamma gene rearrangements confirmed the T-cell lineage of this lymphoma. To our knowledge, this is the first reported case of an EBV-positive T cell lymphoma of the anaplastic large cell subtype following organ transplant.