Immunosurveillance, Immunodeficiency and Lymphoproliferations

  • Stephan H. Oertel
  • Hanno Riess
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 159)


The incidence of malignant lymphomas is significantly higher in patients who have congenital or acquired immunodeficiencies. Although there are some differences between these immunodeficiency-associated lymphoproliferative disorders (lALD), they share several features: a tendency to present in extranodal sites, particularly the central nervous system and gastrointestinal tract, rapid clinical progression when untreated, diffuse large cell histology, B-cell origin and association with the Epstein-Barr virus (EBV). In the presence of disturbed T-cell function EBV may induce not only prolonged proliferation but also transformation of B-cells. In patients with primary, congenital immunodeficiency the incidence of lALD ranges from 0.7% for patients with X-linked agammaglobulinemia to 12–15% in patients with ataxia telangiectasia. In patients with post-transplant lymphoproliferative disorders (PT-LPD) the incidence varies from 0.5% after bone marrow transplantation to 10% after heart-lung transplantation. PT-LPD are often characterized by a polymorphic cell population. Recent studies identified three categories: plasmacytic hyperplasia, poly morphic lymphoproliferation and B-cell non-Hodgkin’s lymphoma (NHL). The plasmacytic hyperplasias are of polyclonal composition, while polymorphic lymphoproliferations and NHL are monoclonal. The precise risk of lymphoma development in HIV infection is not defined, but estimates suggest a prevalence of 3–4%. HIV-related NHLs are divisible by site of manifestation into systemic, primary central nervous system and body-cavity lymphomas, and by pathology into Burkitfs and Burkitt’s-like lymphoma, and diffuse large cell lymphoma (DLCL). In about 90% of cases these lymphomas are of monoclonal B-cell composition. Recent experiences suggest a link between therapy with immunosuppressive drugs (methotrexate, azathioprine, cyclophospamide, etc.) and development of lALD, best supported by the increased rate of lALD in patients with rheumatoid arthritis who receive methotrexate therapy. The occurrence of lALD demonstrates the importance of competent immunosurveillance in the development of lymphoid neoplasias, which may have therapeutic relevance too.


Human Immunodeficiency Virus Human Immunodeficiency Virus Infection Lymphoproliferative Disorder Ataxia Telangiectasia Diffuse Large Cell Lymphoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ehrlich P (1957) Über den jetzigen Stand der Karzinomforschung. In: The collected papers of Paul Ehrlich, vol 2, p 550Google Scholar
  2. 2.
    Prang NS, Hornef MW, Jager M, et al (1997) Lytic replication of Epstein-Barr virus in the peripheral blood: analysis of viral gene expression in B lympho cytes during infectious mononucleosis and in the normal carrier state. Blood 5:2114–2116Google Scholar
  3. 3.
    Rosen FS, Cooper MD, Wedgwood RJ (1984) The primary immunodeficiencie N Engl J Med 311:235–242PubMedCrossRefGoogle Scholar
  4. 4.
    Filipovich AH, Shapiro R, Robison L, et al (1990) Lymphoproliferative disor-ders associated with immunodeficiency. In: Margrath IT (ed) The non-Hodg-kin’s lymphomas. Edward Arnold, London, pp 135–154Google Scholar
  5. 5.
    Elenitoba-Johnson KSJ, Jaffe ESI (1997) Lymphoproliferative disorders associated with congenital immunodeficiencies. Semin Diagn Pathol 1:35–47Google Scholar
  6. 6.
    Knowles DM (1999) Immunodeficiency-associated lymphoproliferative disorders Mod Pathol 2:200–217Google Scholar
  7. 7.
    Seidemann K, Tiemann M, Henze G, et al (1999) Therapy for non-Hodgkin lymphoma in children with primary immunodeficiency: analysis of 19 patients from the BFM trials. Med Pediatr Oncol 6:536–544CrossRefGoogle Scholar
  8. 8.
    Penn I, Hammond W, Brettschneider L, Starzl TE (1969) Malignant lymphomas in transplantation patients. Transplant Proc 1:106–112PubMedGoogle Scholar
  9. 9.
    Young L, Alfieri C, Hennessy K, et al (1989) Expression of Epstein-Barr virus trans format ion-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med 321:1080–1085PubMedCrossRefGoogle Scholar
  10. 10.
    Knowles DM, Cesarmen E, Chadburn A, Frizzera G, et al (1995) Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. Blood 85:552–565PubMedGoogle Scholar
  11. 11.
    Starzl TE, Nalesnik MA, Portier KA, et al (1984) Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1:583–587PubMedCrossRefGoogle Scholar
  12. 12.
    Oertel SH, Ruhnke M, Anagnostopoulos I, et al (1999) Treatment of Epstein-Barr virus-induced post-transplant lymphoproliferative disorder (PT-LPD) with Foscarnet alone in an adult after simultaneous heart and renal translantation. Transplant, pp 765–767Google Scholar
  13. 13.
    Faller DV, Hermine O, Small T, et al (2000) Phase I/II trial of arginine butyrate to induce viral TK gene expression in Epstein-Barr virus associated lymphomas. Blood 11:577Google Scholar
  14. 14.
    Oertel SH, Anagnostopoulos I, Bechstein WO, et al (2000) Treatment of posttransplant lymphoproliferative disorder with the anti-CD20 monoclonal antibody rituximab alone in an adult after liver transplantation: a new drug in therapy of patients with PT-LPD after solid organ transplantation? Transplantation 3:430–432CrossRefGoogle Scholar
  15. 15.
    Rooney CM, Smith CA, Ng CY, et al (1998) Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogenic transplant recipients. Blood 5:1549–1555Google Scholar
  16. 16.
    Haddad E, Pazesny S, Leblond V, et al (2001) Treatment of B-Iymphoproliferative disorders with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1–2 clinical trial Blood 6:1590–1597CrossRefGoogle Scholar
  17. 17.
    Garrett TJ, Chadburn A, Knowles DM, et al (1993) Post-transplant lymphoproliferative disorders treated with cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy. Cancer 72:2782–2785PubMedCrossRefGoogle Scholar
  18. 18.
    Cote TR, Biggar RJ, Rosenberg PS, et al (1997) Non-Hodgkin’s lymphoma among people with AIDS: incidence, presentation and public health burden. Int I Cancer 73:645–650CrossRefGoogle Scholar
  19. 19.
    Knowles DM (1997) The molecular pathology of AIDS-related non-Hodgkin’s lymphoma. Semin Diagn Pathol 14:67–82PubMedGoogle Scholar
  20. 20.
    Tirelli, M, Spina U, laeger E, Higra PL, Blanc AM, Liberati A, Benci JA (2001) Sparano. Infusional CDE with rituximab for the treatment of HIV-associated NHL: preliminary results of a phase I/II study. Ree Results Cancer Res, p 159Google Scholar
  21. 21.
    Schneider U, Ruhnke M, Delecluse Hf, et al (2000) Regression of Epstein-Barr virus associated lymphoproliferative disorders in patients with acquired immunodeficiency syndrome during therapy with foscarnet. Ann Hematol 79:214–216PubMedCrossRefGoogle Scholar
  22. 22.
    Kamel OW (1997) Iatrogenic lymphoproliferative disorders in nontransplantational settings. Semin Diagn Pathol 1:27–34Google Scholar
  23. 23.
    Thomasen RW, Graig EE, Banks PM, et al (1996) Epstein-Barr virus and lymphoproliferation in methotrexate treated rheumatoid arthritis. Mod Pathol 9:261–266Google Scholar
  24. 24.
    Kurzrock R, Strom SS, Estey E, et al (1997) Second cancer risk in hairy cell leukemia: analysis of 350 patients. J Clin Oncol 5:1803–1810Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Stephan H. Oertel
    • 1
  • Hanno Riess
    • 1
  1. 1.Hämatologie und OnkologieHumboldt-Universität BerlinBerlinGermany

Personalised recommendations