Opps we did it again

The most important thing to understand is that I am extremely grateful for all the help and assistance by the staff of the General Hospital in Ottawa. It is incredible that such a group of caring, competent individuals have found each other and it is a miracle that they have given me from 58 years of age to 66 years of age. A total of 8 years of extra life.

I believe mistakes were made in my first transplant. The head of the Department of Nephrology disagrees. I will let you decide

Mistake 1: Epstein Barr Virus (EBV) Serology One of the considerations is your EBV Serology. I did not have the virus so I was EBV(-) o seronegative. If I had the virus I would be EBV (+) or seropositive. Negative or Positive, you have it or you do not.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication following organ transplantation. The greatest risk is seen in Epstein-Barr virus (EBV)-seronegative patients receiving allografts from EBV-seropositive donors.

N Babel 1 , L Gabdrakhmanova, M Hammer, C Rosenberger, M Oppert, H-D Volk, P Reinke Transpl Infect Dis 2005 Sep-Dec;7(3-4):133-6.
Induction of pre-transplant Epstein-Barr virus (EBV) infection by donor blood transfusion in EBV-seronegative recipients may reduce risk of post-transplant lymphoproliferative disease in adolescent renal transplant patients: report of two cases

Seronegative patient, seropositive donour, that was my scenario. That was the basic mistake.

Mistake #2 I was told a kidney was available and I was told there was a 1% chance I would get the EBV Virus. If I had been like 90% of the population and was EBV(+) the statement would have been true.

[EBV reactivates in] organ transplant recipients an average of 1% to 2% in adults (2)

2. Hanto DW, Frizzera G, Gajl-Peczalska KJ, et al. Epstein-Barr virus (EBV) induced B-cell lymphoma after renal transplantation. N Engl J Med 1982;306:913-8. [PubMed] [Google Scholar]

Unfortunately for me as an EBV – patient, receiving an EBV+ kidney the chance of me getting EBV was closer to 100%. The doctor got the numbers right, just for the wrong patient.

In view of the fact that in EBV-seronegative transplant recipients, EBV infection rates are high, approaching 100% within three months after transplantation …. in the EBV-seronegative transplant population (8).

8. Ho M, Miller G, Atchison RW, et al. Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: The role of primary infection. J Infect Dis 1985;152:876-8. [PMC free article] [PubMed] [Google Scholar]

The doctor explaining things to me got the incidence off by 98%.

Mistake #3 The doctor went on to explain that EBV was not a serious infection.

True for the general population exposed at a young age and not on immune suppressants. NOT true for those who are EBV- being exposed to the virus for the first time, as I was and then put on immune suppressants due to a kidney transplant.

Under conditions of severe T cell immunosuppression, which prevail in … transplant recipients, EBV-infected B cells may expand unchecked, resulting in malignant lymphoproliferation. In this context, the virus is able to transform and immortalize B lymphocytes, leading to their uncontrolled proliferation

Pope JH, Horne MK, Scott W. Transformation of foetal human leukocytes in vitro by filtrates of a human leukemic cell line containing herpes-like virus. Int J Cancer 1968;3:857-66. [PubMed] [Google Scholar]

The uncontrolled proliferation is something called Post-transplant lymphoproliferative disorder (PTLD). To be clear I did not get PTLD as of year 6 of my transpant. However the EBV required a reduction in my immune suppression.

The clinical management of PTLD entails the reduction of immunosuppressive medication with the potential complication of rejection. Because of the difficulties that may be encountered in distinguishing EBV-positive lymphoid infiltrates from rejection (19), markers have been sought to confirm the presence of EBV and to evaluate the relative risk for PTLD development in different clinical scenarios.

19. Howard TK, Klintmalm GB, Stone MJ. Lymphoproliferative disorder masquerading as rejection in liver transplant recipients – an early aggressive tumor with atypical presentation. Transplantation 1992;53:1145-7. [PubMed] [Google Scholar]

Mistake 4: Treatment incomplete, I will not know until its to late.

Evidence of EBV infection is then followed by one or more of the following in an effort to prevent PTLD:

reduction of immunosuppressionyes
antiviral therapy, ??ganciclovir, valgancicloviryes valganclor 3 monts after transplant
Intravenous immunoglobulin (IVIG)no
monoclonal antibody therapy directed toward infected B lymphocytes (e.g. rituximab)no
infusion of EBV-specific cytotoxic T lymphocytesno

Pre-emptive immunotherapy with rituximab
Of the 20 recipients who became viremic, 6 (30%) received pre-emptive rituximab before the development of PTLD. Criteria for treatment were based on continued viremia that did not improve or significant symptoms attributed to the infection. All patients meeting these criteria had some concomitant reduction of immunosuppression as well. Of the six recipients receiving pre-emptive rituximab, five cleared their viremia with no recurrence after one dose. One recipient received a second dose of rituximab before viral clearance was complete. No cases of PTLD have occurred within the six recipients pre-emptively treated with rituximab and all have remained completely aviremic during the follow-up time period.