[Post-transplant lymphoproliferative disorders in renal transplantation: two decades of experience]

Nefrologia. 2010;30(6):669-75. doi: 10.3265/Nefrologia.pre2010.Aug.10361.
[Article in Spanish]

Abstract

Introduction: Post-transplant lymphoproliferative disease (PTLD) represents a heterogeneous group of diseases characterised by a proliferation of lymphocytes occurring after solid organ transplantation. Most cases of PTLD are B-cell and their development has been closely associated with the Epstein-Barr virus (EBV), whose proliferation is encouraged by the inhibition of the cytotoxic function of T lymphocytes due to immunosuppressive drug treatment for transplant recipients. Several risk factors have been described for the development of this disorder, such as the seronegative state of the EBV receptor, the degree of overall net immunosuppression, especially with the use of monoclonal and polyclonal antibodies, acute rejection and cytomegalovirus (CMV) disease.

Material and method: We studied the incidence of PTLD and its relationship with EBV as well as its evolution and possible risk factors in 1176 adult recipients of cadaveric renal transplantation performed in our hospital between 1988 and 2009, with a follow-up of 1-255 months. The presence of EBV in the lymphoproliferative tissue was determined using in situ hybridisation. We analysed the incidence of PTLD over two time periods, 1988-1998 and 1999-2009 with 472 and 704 patients respectively.

Results: A total of 28 recipients (2.38%), 22 men and 6 women with a mean age of 46.5 (15.36) years (18-70 years) with a mean post-transplant evolution of 72.9 (56.3) months (1-180 months), developed PTLD. Thirteen (46.4%) did not show any of the classic risk factors described. The presence of EBV in lymphoproliferative tissue was detected in 18 out of 26 patients studied (69.2%). In terms of histology, 25 out of 28 were type B (89.2%). Ten out of 28 patients diagnosed (35.7%) received treatment with rituximab, six died during the follow-up, five as a direct result of their illness. The incidence for the two time periods was very similar for both groups, with 0.003922 cases/year-patient in the 1988-1998 period and 0.003995 cases/year-patient in the 1999-2009 period. Overall post-transplant survival for patients with PTLD was 73.6% at 5 years and 36.9% at 10 years, versus 87.8% and 75.9% for disease-free recipients (P<.0001). We calculated a graft survival of 62.6% at 5 years and 27.3% at 10 years versus 72.4% and 53.9% for grafts in disease-free recipients (P<.0001). In our study, patient survival one year after presenting the disease was 30.9% and 23.2% at year two. For the graft, survival was 15.5% and 7.7%, respectively.

Conclusions: We conclude that PTLD is a disorder that is generally type B; it is significantly associated with EBV. Its incidence has not changed over time and half of all PTLD cases had no identifiable risk factors, which led to a poor prognosis despite the development of new treatments.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B-Lymphocytes / pathology
  • B-Lymphocytes / virology
  • Cadaver
  • Epstein-Barr Virus Infections / epidemiology
  • Epstein-Barr Virus Infections / transmission
  • Epstein-Barr Virus Infections / virology
  • Female
  • Follow-Up Studies
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunocompromised Host
  • Immunosuppression Therapy / adverse effects
  • Incidence
  • Kidney Transplantation* / adverse effects
  • Lymphoproliferative Disorders / epidemiology*
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / virology
  • Male
  • Middle Aged
  • Postoperative Complications / epidemiology*
  • Postoperative Complications / etiology
  • Risk Factors
  • Spain / epidemiology
  • Virus Activation
  • Young Adult