Transplant patients lymphoproliferative disorders

In patients with transplanted organs ciclosporin is associated with a small but significant risk of Epstein-Barr virus-associated lymphoproliferative disorders. 

In contrast, there have been several isolated reports of methotrexate-induced lymphomas (SEDA-21, 388) (SEDA-22, 417) (115,116). The pathological features in these cases have ranged from benign lymphoid hyperplasia to non-Hodgkin s lymphoma, and more rarely Hodgkin s disease (115), and patients usually had the typical features of lymphoproliferative disorders as found in immunosuppressed patients, that is, transplant patients or patients with congenital or acquired immune deficiency syndromes. Exceptionally, cases of pseudolymphoma have also been reported (SEDA-21, 389). 

The incidence of adverse effects (for example neurotoxicity, nephrotoxicity, and hyperglycemia), particularly those requiring drug withdrawal, was initially found to be higher in tacroUmus-treated Uver transplant patients, but subsequently fell after the initial tacrolimus dose was reduced. This was in accordance with the results of very early trials, which showed that the initially proposed dose of tacrolimus was too high (3). In subsequent studies, tacrolimus and ciclosporin had a similar spectrum of adverse effects for nephrotoxicity, infectious complications, and lymphoproliferative disorders, and long-term adverse effects occurred at comparable rates, that is less than 2% (SED-13,1130) (SEDA-21, 390). 

Using the same design in patients who received kidney transplants, patient and graft survival were similar in the two groups, with superior renal function in patients treated with belatacept [5 "]. However, in this study, there were a higher incidence and grade of graft rejection and post-transplant lymphoproliferative disorders in those who received belatacept. 

Tumorigenidty Lymphoproliferative disorders have been reported after pancreas transplantation following alemtuzumab induction in 100 patients [146. Epstein-Barr virus-positive immunodeficiency lymphoma after therapy with alemtuzumab... 

In a study of alemtuzumab for the treatment of acute rejection in 15 kidney transplant recipients, the rates of malignancies in alemtuzumab-treated patients were not increased during 12 years follow-up in particular, no patients treated with alemtuzumab for acute rejection developed post-transplantation lymphoproliferative disorders [148 ]. 

Late episodes of acute rejection are uncommon, and usually relate to poor patient compliance or inadequate levels of immunosuppression. The pathophysiology of chronic rejection is poorly understood, and can lead to graft loss. The incidence of chronic rejection has fallen progressively to approximately 5% over the past 10 years. Over-immunosuppression can lead to opportunistic bacterial infections and increased incidence of malignant disorders. Opportunistic infections such as legionellosis, nocardiosis, and tuberculosis occur between the 1st and I2th month post-transplant. Immunosuppressive treatment can be associated with Epstein Barr virus infection, and the development of post-transplantation lymphoproliferative disorder (Fig. 4.1.8). 

Viral infections that occur after transplantation are not limited to the lung. Herpes simplex infections are frequent early after the procedure, manifesting as oral vesicles or ulcerations. Less frequent is genital involvement by herpes simple virus, hepatitis or encephalitis. Herpes zoster and varicella reactivate in most patients, particularly if aciclovir prophylaxis is discontinued. Occasionally, severe cerebral arteritis or pneumonia caused by this virus may occur. CMV infection is frequent after transplantation and has to be regularly monitored by antigenemia and/or PCR for early treatment avoiding CMV disease. Epstein Barr virus (EBV) infection and EBV-associated lymphoproliferative disorders have also to be tested on a regular basis, especially in transplants with in... 

Post-transplant malignancies in HSC transplantation patients are seven times more common than primary cancer in the general population. Posttransplant malignancies include solid tumors, hematologic neoplasms, and post-transplantation lymphoproliferative disorder (PTLD) (Libshitz et al. 1978 Worthy et al. 1997). 

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