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Virostatic Therapy for Advanced Lymphoproliferation Associated with the Epstein–Barr Virus in an HIV-Infected Patient

N Engl J Med 2000; 342:440-441February 10, 2000

Article

To the Editor:

Patients infected with the human immunodeficiency virus (HIV) are at risk for malignant non-Hodgkin's lymphoma of B-cell origin.1 We describe a patient with morphologic features of polymorphic B-cell lymphoproliferation similar to those observed after solid-organ transplantation.2

A 36-year-old homosexual man presented with dysuria, fecaluria, watery diarrhea, fever, and weight loss of 8 kg within the previous two months. HIV infection had been diagnosed in 1995. The patient had an initial CD4 T-cell count of 50 cells per microliter of blood and a viral load of 140,000 HIV copies per milliliter. He had received highly active antiretroviral therapy (zidovudine, 250 mg twice a day; lamivudine, 150 mg twice a day; and saquinavir, 600 mg three times a day) for four weeks before admission. Imaging techniques revealed an 8-cm retrovesical tumor that had infiltrated the bladder, rectum, sigmoid colon, ileum, and right ureter, causing hydronephrosis as well as vesicoileal and vesicorectal fistulas.

Extensive surgery was performed, with ileocecal and anterior rectal resection, partial resection and reconstruction of the urinary bladder, and ureteroplasty. Histologic examination of the resected tumor revealed a diffuse infiltrate of polymorphous lymphoid cells and large necrotic areas that extended beyond the margins of the resection. The infiltrate was rich in blasts and cells often associated with plasma-cell differentiation. Immunostaining indicated a B-cell phenotype in the infiltrate, a growth fraction of 90 percent, and the expression of Epstein–Barr virus (EBV)–encoded latent membrane protein 1 and EBV nuclear antigen 2. Analysis of immunoglobulin gene rearrangement by the polymerase chain reaction showed a polyclonal B-cell population.

HIV-related malignant lymphomas are usually managed by cytostatic chemotherapy, but with a poor outcome.3 The recent observation that virostatic therapy may be beneficial in treating post-transplantation lymphoproliferation induced by EBV led us to opt for such an approach.4 The patient received foscarnet (180 mg per kilogram of body weight) for three weeks. After the first week, antiretroviral therapy was resumed (stavudine, 40 mg twice a day; lamivudine, 150 mg twice a day; saquinavir, 400 mg twice a day; and ritonavir, 400 mg twice a day). The patient recovered rapidly, gained weight, and regained control of bowel and urinary function. During a follow-up period of 20 months, he has stayed well and has returned to work. There has been no evidence of relapse or progression of disease. HIV replication has been suppressed below the level of detection, and the CD4 count has increased to 310 cells per microliter of blood.

The length of survival and performance status of this patient by far exceed those reported with cytostatic chemotherapy.5 We therefore consider virostatic therapy to be a promising approach for diffusely growing extranodal B-cell lymphoproliferation driven by EBV infection.

Wolfgang Schmidt, M.D.
Ioannis Anagnostopoulos, M.D.
Hans Scherübl, M.D.
University Medical Center Benjamin Franklin, D-12200 Berlin, Germany

5 References

1. 1

   Herndier BG, Kaplan LD, McGrath MS. Pathogenesis of AIDS lymphomas. AIDS 1994;8:1025-1049
   CrossRef | Web of Science | Medline

2. 2

   Frizzera G. Atypical lymphoproliferative disorders. In: Knowles DM, ed. Neoplastic hematopathology. Baltimore: Williams & Wilkins, 1992:459-95.
   

3. 3

   Kaplan LD, Straus DJ, Testa MA, et al. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. N Engl J Med 1997;336:1641-1648
   Full Text | Web of Science | Medline

4. 4

   Oertel SH, Ruhnke MS, Anagnostopoulos I, et al. Treatment of Epstein-Barr virus-induced posttransplantation lymphoproliferative disorder with foscarnet alone in an adult after simultaneous heart and renal transplantation. Transplantation 1999;67:765-767
   CrossRef | Web of Science | Medline

5. 5

   Tirelli U, Spina M, Vaccher E, et al. Clinical evaluation of 451 patients with HIV related non-Hodgkin's lymphoma: experience on the Italian cooperative group on AIDS and tumors (GICAT). Leuk Lymphoma 1995;20:91-96
   CrossRef | Web of Science | Medline

Citing Articles (8)

Citing Articles

1. 1

   Jing Kroll, Shaobing Li, Marilyn Levi, Adriana Weinberg. (2011) Lytic and latent EBV gene expression in transplant recipients with and without post-transplant lymphoproliferative disorder. Journal of Clinical Virology 52:3, 231-235
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2. 2

   Andrew M. Evens, Rupali Roy, Danielle Sterrenberg, Michelle Z. Moll, Amy Chadburn, Leo I. Gordon. (2010) Post-Transplantation Lymphoproliferative Disorders: Diagnosis, Prognosis, and Current Approaches to Therapy. Current Oncology Reports 12:6, 383-394
   CrossRef

3. 3

   Mirvat Ballout, Raphaële Germi, Samira Fafi-Kremer, Josette Guimet, Gerard Barguès, Jean-Marie Seigneurin, Patrice Morand. (2007) Real-time quantitative PCR for assessment of antiviral drug effects against Epstein-Barr virus replication and EBV late mRNA expression. Journal of Virological Methods 143:1, 38-44
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4. 4

   S. Bossolasco, K. I. Falk, M. Ponzoni, N. Ceserani, F. Crippa, A. Lazzarin, A. Linde, P. Cinque. (2006) Ganciclovir Is Associated with Low or Undetectable Epstein-Barr Virus DNA Load in Cerebrospinal Fluid of Patients with HIV-Related Primary Central Nervous System Lymphoma. Clinical Infectious Diseases 42:4, e21-e25
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5. 5

   Stephan H. Oertel, Ioannis Anagnostopoulos, Manfred W. Hummel, Sven Jonas, Hanno B. Riess. (2002) Identification of early antigen BZLF1/ZEBRA protein of Epstein-Barr virus can predict the effectiveness of antiviral treatment in patients with post-transplant lymphoproliferative disease. British Journal of Haematology 118:4, 1120-1123
   CrossRef

6. 6

   Jianguo Tao, Mariusz A Wasik. (2001) Epstein-Barr Virus Associated Polymorphic Lymphoproliferative Disorders Occurring in Nontransplant Settings. Laboratory Investigation 81:4, 429-437
   CrossRef

7. 7

   Laurent Hocqueloux, Félix Agbalika, Eric Oksenhendler, Jean-Michel Molina. (2001) Long-term remission of an AIDS-related primary effusion lymphoma with antiviral therapy. AIDS 15:2, 280-282
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8. 8

   (2000) More on Virostatic Therapy for Advanced Lymphoproliferation Associated with Epstein–Barr Virus in an HIV-Infected Patient. New England Journal of Medicine 343:1, 71-72
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