Long-term survival of a patient with human immunodeficiency virus infection and Hodgkin's lymphoma.

ABSTRACT

When patients infected with human immunodeficiency virus (HIV) are found to have Hodgkin's lymphoma (HL), it is generally advanced, with involvement of extranodal sites including bone marrow, spleen, and liver, and prognosis tends to be unfavorable. We present the case of a 38-year-old white man who had HIV and HL diagnosed in 1990. Despite presenting with stage IV HL, having recurrence of HL after initially attaining remission, and being hospitalized on several occasions for opportunistic infections, he ultimately achieved complete remission of HL and is alive 9 years after initial diagnosis. This case illustrates that although unusual, prolonged survival of an HIV-infected patient with HL associated with poor prognostic features is possible.

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BOTH high and intermediate grade non-Hodgkin's lymphomas and Hodgkin's lymphoma (HL) have an increased incidence in patients infected with HIV. (1) However, it is difficult to assess whether HL is increased in the setting of HIV infection because HL and HIV frequently occur among patients in a similar age group. (2) Nevertheless, some reports indicate that the incidence of HL is increased in patients infected with HIV, though not to the same extent as non-Hodgkin's lymphoma or Kaposi's sarcoma. (3,4)

Several studies have focused on the clinical presentation and behavior of HL in HIV-infected patients. In the setting of HIV infection, HL is increased among intravenous drug abusers. (5-7) Human immunodeficiency virus-related HL is more common in men (5,6) and is characterized by an advanced stage at presentation, the presence of B symptoms (fever, night sweats, or weight loss >10% of body weight), mixed cellularity histology, involvement of bone marrow, and an aggressive clinical course. (5,6,8)

Not surprisingly, therefore, long-term survival of HIV-infected patients with HL is low. One study of 114 patients reported a median survival of 7 months for patients with the acquired immunodeficiency syndrome (AIDS) at the time of HL diagnosis. (5) Based on their findings, Tirelli et al (5) indicated the following favorable risk factors: achievement of complete remission, CD4 counts > 250/[micro]L, and no previous diagnosis of AIDS. However, when the diagnosis of HL precedes that of AIDS, the median survival is still low (20 months). In another stud of 46 cases, projected 3-year survival was 19%. (6)

We describe a patient in whom HIV infection and HL were diagnosed during the same hospitalization. He received chemotherapy, achieved complete remission initially, and had relapse before achieving complete remission again. He is alive 9 years after initial diagnosis.

CASE REPORT

This 29-year-old bisexual white man was admitted to the hospital in September 1990 for evaluation of syncopal episodes. Admission physical examination showed splenomegaly and axillary lymphadenopathy; laboratory data showed severe leukopenia (white blood cell count 2,100/[mm.sup.3]), anemia (hemoglobin value, 6 g/dL), and normal platelet count (249,000/[mm.sup.3]). Biopsy of an axillary lymph node 4 days after admission yielded histologic findings consistent with follicular hyperplasia. Flow cytometric immunophenotyping studies done on a sample from the initial lymph node biopsy revealed 20% B cells and 75% T cells with reduced ratio (0.75) of helper T cells (CD4) to suppressor T cells (CD8). Absolute values of CD4 were not reported. Human immunodeficiency virus infection was subsequently diagnosed with enzyme-linked immunosorbent assay and confirmed by Western blot analysis. Repeated axillary lymph node biopsy 2 weeks after admission led to a diagnosis of HL, lymphocyte depletion type. However, review of the earlier histologic sections showed nodules composed of lacunar-type Reed-Sternberg cells, small lymphocytes, and plasma cells separated by birefringent collagen bands, findings more compatible with the nodular sclerosis type of HL. A staging bone marrow biopsy showed extensive involvement, and stage IV HL was diagnosed.

Radiologic Studies

Computed tomography of the abdomen 1 day after admission showed right subcrural and periaortic lymphadenopathy, as well as splenomegaly. An admission chest x-ray film did not show active cardiopulmonary disease or hilar adenopathy.

Treatment and Follow-Up

The patient received one round of chemotherapy, MOPP-ABV (nine cycles of nitrogen mustard, vincristine, procarbazine, and prednisone [MOPP], alternating with Adriamycin [doxorubicin], bleomycin, and vinblastine [ABV]). After this course, the patient was found to be free of HL. However, 3 years later, in December 1993, right cervical lymphadenopathy recurred. Biopsy of the cervical lymph node showed recurrent nodular sclerosis HL. Staging bone marrow biopsy showed a normocellular specimen without evidence of HL. Another round of MOPPABV (4 cycles) was administered, and the patient achieved complete remission. Seven months later, in July 1994, the patient was hospitalized for treatment of Pneumocystis carinii pneumonia, herpes simplex viral infection, oral candidiasis, and pulmonary cytomegalovirus infection. His CD4 count at the time was 8/mm.sub.3]. Bone marrow biopsy during this hospitalization did not show HL or acid-fast or fungal organisms. He was treated and discharged in August 1994 and was lost to foll ow-up until 4 years later, when he presented with localized axillary adenopathy in March 1998. Lymph node biopsy showed follicular hyperplasia and other reactive changes.

DISCUSSION

In patients with HIV infection and Hodgkin's disease, the prognosis is usually poor because of advanced disease at presentation, unfavorable histologic subtype, aggressive clinical course, and associated opportunistic infections. (5) Reported causes of death have included infection, HL, a combination of both infection and HL, or treatment-related toxicities. (5)

This HIV-positive man had stage IV nodular sclerosis HL, with extensive bone marrow involvement. In one series of 45 cases of HIV-associated HL, the overall incidence of bone marrow involvement was 24%. (8) While 40% of the patients (18 of 45) in the same series had nodular sclerosis ML, the incidence of marrow involvement in the specific subtype was not provided. However, less than 10% of patients who have nodular sclerosis HL without H1V infection are reported to have bone marrow involvement at the time of diagnosis. (9, 10) Thus, our patient had an unusually aggressive form of nodular sclerosis HL.

Despite the presence of clinically aggressive disease, this 29-year-old man achieved complete remission but had relapse after 3 years. He again attained complete remission with additional chemotherapy and remained free of disease for 9 years, even though he had several opportunistic infections. This is unusual, since MW-associated HLs are notoriously difficult to teat, despite routine use of granulocyte colony-stimulating factor (G-CSF), as shown by Levine et al. (11) Of the 21 patients studied by these authors, 10 had life-threatening neutropenia, despite G-CSF administration. These authors documented a 29% incidence of opportunistic infections, with a median survival of 1.5 years. (11) Although durable long-term remission and cure of advanced stage ML in patients with HIV infection is unusual, a small number of patients in one large series of 114 patients have had such favorable clinical outcome. (10)

References

(1.) O'Connor PG, Scadden DT: AIDS oncology. Infect Dis Clin North Am 2000; 14:964

(2.) Medeiros LJ, Greiner TC: Hodgkin's disease. Cancer 1995; 75(suppl):357

(3.) Hessol NA, Katz MH, Liu JY, et al: Increased incidence of Hodgkin's disease in homosexual men with HIV infection. Ann Intern Med 1992; 117:309

(4.) Lyter Dw, Kingsley LA, Rinaldo CR, et al: Malignancies in the Multicenter AIDS Cohort Study (MACS), 1984-1994. Proc Am Soc Clin Oncol 1996; 15:852

(5.) Tirelli U, Errante D, Dolcetti R, et al: Hodgkin's disease and human immunodeficiency virus infection: clinicopathologic and virologicc features of 114 patients from the Italian Cooperative Group on AIDS and Tumors. J Clin Oncol 1995; 13:1758

(6.) Rubio R, for the Cooperative Study Group of Malignancies Associated with HIV Infection of Madrid: Hodgkin's disease associated with human immunodeficiency virus infection. Cancer 1994; 73:2400

(7.) Andrieu JM, Roithmann 5, Tourani JM, et al: Hodgkin's disease during HIVI infection: the French Registry experience. Ann Oncol 1994; 5:S37

(8.) Levy R, Colonna P, Tourani JM, et al: Human immunodeficiency virus associated Hodgkin's disease: report of 45 cases from the French Registry of HIV-Associated Tumors. Leuk Lymph 1995; 16:451

(9.) O'Carroll DI, McKenna RW, Brunning RD: Bone marrow manifestations of Hodgkin's disease. Cancer 1976; 38:1717

(10.) Rosenberg SA: Hodgkin's disease of the bone marrow. Cancer Res 1971; 31:1814

(11.) Levine AM, Li P, Cheung T, et al: Chemotherapy consisting of doxorubicin, bleomycin, cinblastine, and dacarbazine with granulocyte-colony-stimulating factor in HIV-infected patients with newly diagnosed Hodgkin's disease: a prospective, multi-institutional AIDS clinical trials group study (ACTG 149). J AIDS 2000; 24:444

RELATED ARTICLE: KEY POINTS

* HIV-infected individuals with Hodgkin's lymphoma tend to have an advanced stage of lymphoma at diagnosis.

* HIV-infected individuals with Hodgkin's lymphoma have a very unfavorable prognosis, with increased morbidity and mortality.

* Although extremely unlikely, long-term survival of HIV-infected individuals with Hodgkin's lymphoma is possible.

From the Departments of Pathology and Medicine, University of South Alabama, Mobile.

Reprint requests to A. Hafeez Diwan, MD, PhD, 1922 7th Ave 5, KB 506, Birmingham, AL 35233.