Hodgkin's Disease in Patients Infected with Human Immunodeficiency Virus: Frequency, Presentation and Clinical Outcome

We report the frequency, presenting characteristics, progression-free survival, event-free survival, overall survival and AIDS-free survival of patients with previously untreated Hodgkin's disease (HD) in the setting of infection by human immunodeficiency virus (HIV). To accomplish this we retrospectively reviewed all untreated patients presenting to the University of Texas M.D. Anderson Cancer Center between July 1985 and August 1999 with HD and HIV infection. All available records were reviewed to determine presentation, clinical characteristics, treatment outcome, progression-free survival and overall survival. We identified 887 patients with HD and 3,500 with Non-Hodgkin's Lymphoma (NHL). The ratio of NHL to HD in HIV-negative versus HIV-positive patients was 3.9 versus 6.9, respectively. There were 14 HIV-positive patients with HD and 97 with NHL. The median age of the HIV-positive HD patients was 33 years, and 13 were male. Three patients had Acquired Immune Deficiency syndrome (AIDS) at the time of HD diagnosis, and seven had B-symptoms. Ann Arbor stage was I in one, II in three, III in four and IV in six patients. Mixed cellularity histology was seen in eight, bone marrow involvement in five and extranodal disease in seven patients. Four patients had elevated serum lactate dehydrogenase, three low serum albumin, and nine elevated serum β2-microglobulin, The median CD4 count was 160/μl. Eleven patients received ABVD or equivalent regimens, followed by radiotherapy in five. One patient was treated with COPP and radiotherapy, one with NOVP and radiotherapy and one only with radiotherapy. All patients received some antiretroviral therapy, but it was variable over the years. With a median follow-up of 64 months for survivors, the projected 5-year progression-free survival was 64%, event-free survival 45%, overall survival 54% and AIDS-free survival 45%. Six patients died of complications arising from HIV infection, including one patient who had preexisting AIDS at HD presentation. Two patients died of HD, without developing other conditions diagnostic of AIDS. We conclude that in our referral patient population HIV infection is associated with preferential development of NHL rather than HD, which appears curable with standard treatment regimens. Since HIV-related deaths exceed those caused by HD, future investigation should focus on integration of chemotherapy and highly active antiretroviral therapy.

[1]  U. Tirelli,et al.  Human immunodeficiency virus-associated Hodgkin's disease. , 2000, Seminars in oncology.

[2]  H. Stein,et al.  Hodgkin and reed-sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. , 2000, Blood.

[3]  G. Bonadonna,et al.  Elevated pretreatment serum levels of Il-10 are associated with a poor prognosis in hodgkin's disease, the Milan Cancer Institute Experience , 2000, Medical oncology.

[4]  K. Kliche,et al.  Interleukin-10 levels are often elevated in serum of adults with Hodgkin's disease and are associated with inferior failure-free survival. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  L. Larocca,et al.  Human immunodeficiency virus-associated Hodgkin's disease derives from post-germinal center B cells. , 1999, Blood.

[6]  S. Frøland,et al.  IL‐10 in HIV infection: increasing serum IL‐10 levels with disease progression—down‐regulatory effect of potent anti‐retroviral therapy , 1999, Clinical and experimental immunology.

[7]  R. Talamini,et al.  Hodgkin's disease in 35 patients with HIV infection: an experience with epirubicin, bleomycin, vinblastine and prednisone chemotherapy in combination with antiretroviral therapy and primary use of G-CSF. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[8]  J. Goedert,et al.  Spectrum of AIDS-associated malignant disorders , 1998, The Lancet.

[9]  A. Tulpule,et al.  PRELIMINARY RESULTS OF AIDS CLINICAL TRIALS GROUP (ACTG) STUDY #149: PHASE II TRIAL OF ABVD CHEMOTHERAPY WITH G-CSF IN HIV INFECTED PATIENTS WITH HODGKIN'S DISEASE (HD): S7 , 1997 .

[10]  E. Campo,et al.  Pathological, immunological, and molecular features of Hodgkin's disease associated with HIV infection. Comparison with ordinary hodgkin's disease. , 1996, The American journal of surgical pathology.

[11]  A. Levine HIV-associated Hodgkin's disease. Biologic and clinical aspects. , 1996, Hematology/oncology clinics of North America.

[12]  L. Rassenti,et al.  Favored use of immunoglobulin V(H)4 Genes in AIDS-associated B-cell lymphoma. , 1996, Blood.

[13]  M. Gulley,et al.  Human immunodeficiency virus-associated Hodgkin's disease contains latent, not replicative, Epstein-Barr virus. , 1995, Human pathology.

[14]  S. Franceschi,et al.  Hodgkin's disease and human immunodeficiency virus infection: clinicopathologic and virologic features of 114 patients from the Italian Cooperative Group on AIDS and Tumors. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  D. Scadden,et al.  Interleukin-10 is an autocrine growth factor for acquired immunodeficiency syndrome-related B-cell lymphoma. , 1995, Blood.

[16]  R Fischer,et al.  Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Gaidano,et al.  Two acquired immunodeficiency syndrome-associated Burkitt's lymphomas produce specific anti-i IgM cold agglutinins using somatically mutated VH4-21 segments. , 1994, Blood.

[18]  R. Rubio Hodgkin'S disease associated with human immunodeficiency virus infection. A clinical study of 46 cases , 1994, Cancer.

[19]  V. Ng,et al.  IgMs produced by two acquired immune deficiency syndrome lymphoma cell lines: Ig binding specificity and VH-gene putative somatic mutation analysis [published erratum appears in Blood 1994 Aug 1;84(3):995] , 1994 .

[20]  Martine,et al.  Epstein-Barr virus-latent gene expression and tumor cell phenotype in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Correlation of lymphoma phenotype with three distinct patterns of viral latency. , 1993, The American journal of pathology.

[21]  A. Carbone,et al.  Human immunodeficiency virus-associated systemic lymphomas may be subdivided into two main groups according to Epstein-Barr viral latent gene expression. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  M. Raphael,et al.  Hodgkin's disease during HIV1 infection: The French Registry Experience , 1993 .

[23]  D. Serraino,et al.  Hodgkin Disease and HIV , 1993, Annals of Internal Medicine.

[24]  Jennifer Y. Liu,et al.  Increased Incidence of Hodgkin Disease in Homosexual Men with HIV Infection , 1992, Annals of Internal Medicine.

[25]  J. Diebold,et al.  Frequent expression of Epstein‐Barr virus latent membrane protein‐1 in tumour cells of Hodgkin's disease in HIV‐positive patients , 1992, The Journal of pathology.

[26]  S. Monfardini,et al.  A clinicopathologic study of lymphoid neoplasias associated with human immunodeficiency virus infection in Italy , 1991, Cancer.

[27]  I. Maclennan,et al.  Germinal center cells express bcl‐2 protein after activation by signals which prevent their entry into apoptosis , 1991, European journal of immunology.

[28]  C. Metroka,et al.  Hodgkin's disease and AIDS. Twenty-three new cases and a review of the literature. , 1991, Hematology/oncology clinics of North America.

[29]  Gwyn T. Williams,et al.  Activation of Epstein–Barr virus latent genes protects human B cells from death by apoptosis , 1991, Nature.

[30]  P. Sordillo,et al.  Hiv‐associated Hodgkin disease: A clinical study of 18 cases and review of the literature , 1991, American journal of hematology.

[31]  R. Foà,et al.  Hodgkir's disease in 63 intravenous drug users infected with human immunodeficiency virus , 1991 .

[32]  S. Uccini,et al.  HIGH FREQUENCY OF EPSTEIN-BARR VIRUS GENOME IN HIV-POSITIVE PATIENTS WITH HODGKIN'S DISEASE , 1989, The Lancet.

[33]  L. Bernstein,et al.  AIDS-related secular trends in cancer in Los Angeles County men: a comparison by marital status. , 1989, Cancer research.

[34]  B. Clarkson,et al.  AIDS‐related lymphoid neoplasia. The memorial hospital experience , 1988, Cancer.

[35]  L. Kaplan AIDS-associated lymphomas. , 1988, Infectious disease clinics of North America.

[36]  P. Pelicci,et al.  Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS). The New York University Medical Center experience with 105 patients (1981-1986). , 1988, Annals of internal medicine.

[37]  J. Goedert,et al.  Cancer trends in a population at risk of acquired immunodeficiency syndrome. , 1985, Journal of the National Cancer Institute.

[38]  Giffen Jw Hodgkin's disease , 1980, Bone Marrow Transplantation.

[39]  G. Bonadonna,et al.  Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP , 1975, Cancer.

[40]  M Tubiana,et al.  Report of the Committee on Hodgkin's Disease Staging Classification. , 1971, Cancer research.

[41]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[42]  John McGrath,et al.  Hodgkin’s Disease , 1933, JAMA.

[43]  V. Ng,et al.  IgMs produced by two acquired immune deficiency syndrome lymphoma cell lines: Ig binding specificity and VH-gene putative somatic mutation analysis. , 1994, Blood.

[44]  F. Cabanillas,et al.  Hodgkin's disease with a mediastinal mass greater than 10 cm: results of four different treatment approaches. , 1994, Annals of oncology : official journal of the European Society for Medical Oncology.

[45]  R. Rubio Hodgkin's disease associated with human immunodeficiency virus infection. A clinical study of 46 cases. Cooperative Study Group of Malignancies Associated with HIV Infection of Madrid. , 1994, Cancer.

[46]  L. Fuller,et al.  Treatment of early stages of Hodgkin's disease with novantrone, vincristine, vinblastine, prednisone, and radiotherapy. , 1994, Seminars in hematology.

[47]  G. Lemp,et al.  The spectrum of acquired immunodeficiency syndrome (AIDS)-associated malignancies in San Francisco, 1980-1987. , 1993, American journal of epidemiology.

[48]  M. Raphael,et al.  Hodgkin's disease during HIV1 infection: the French registry experience. French Registry of HIV-associated Tumors. , 1993, Annals of oncology : official journal of the European Society for Medical Oncology.

[49]  C. Moran,et al.  Epstein-Barr virus in Hodgkin's disease from patients with human immunodeficiency virus infection. , 1992, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[50]  J. Andrieu,et al.  Clinical and biological characteristics of malignant lymphomas in HIV-infected patients. , 1992, European journal of cancer.

[51]  M. Raphaël,et al.  [Hodgkin's disease associated with HIV infection: clinical characteristics and development. French registry of tumors associated with HIV infection]. , 1992, Bulletin du cancer.

[52]  J. Strauchen,et al.  Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells. , 1991, Cancer.

[53]  S. Hamilton-Dutoit,et al.  AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization. , 1991, The American journal of pathology.

[54]  S. Akira,et al.  Biological and clinical aspects of , 1990 .

[55]  S. Horning,et al.  Hodgkin's disease in homosexual men with generalized lymphadenopathy. , 1985, Annals of internal medicine.