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1246 Part IX: Lymphocytes and Plasma Cells Chapter 81: Hematologic Manifestations of Acquired Immunodeficiency Syndrome 1247

a viral homologue of interleukin (IL)-6. Other HHV8-related disor- HUMAN IMMUNODEFICIENCY
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ders include Castleman disease and Kaposi sarcoma, both of which may VIRUS–ASSOCIATED HODGKIN LYMPHOMA
coexist with primary effusion lymphoma in a substantial proportion of
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patients. Patients may present with dyspnea from pleural effusions or Hodgkin lymphoma tends to occur at moderate levels immunosup-
new-onset ascites. A high index of suspicion for lymphoma is needed so pression in HIV+ patients, unlike NHL, where the risk increases as the
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that appropriate samples are sent to Hematopathology for analysis. Pri- CD4 count decreases. A retrospective cohort study from the Veterans
mary effusion lymphoma cells have an immunoblastic, plasmablastic, or Administration Clinical Case Registry from 1985 to 2010 showed that
anaplastic appearance and are CD45+ and CD30+; CD20 is expressed Hodgkin lymphoma was most common in patients with CD4 counts
less than 5 percent of the time. The malignant cells are latently infected of 200 to 350 cells/μL. The risk was highest in the first year after start-
with HHV8, which is detectable by immunocytochemistry. There are no ing ART, and was lower in people with a greater percent of time with
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large prospective studies of treatment of primary effusion lymphoma, a an undetectable viral load. Data from 14 U.S. Cancer Registries rep-
consequence of its rarity, and the majority of the available information resenting 25 percent of the U.S. population was used to compare the
is derived from retrospective case series. There are a few case reports of clinical features of HIV+ and HIV– patients with Hodgkin lymphoma
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complete remission following initiation of ART without chemotherapy, in the ART era. In this study, Hodgkin lymphoma occurring in HIV+
and ART should be a component of the treatment plan. Patients have people was shown to be a clinically aggressive disease. Of the 22,355
been treated with CHOP, EPOCH, and other regimens. Approximately patients with Hodgkin lymphoma, 3.8 percent were HIV+. However
50 percent of patients with primary effusion lymphoma achieve a com- this percentage varied depending on sex, ethnicity, and age. Prevalent
plete response, but relapse within the next few months is common, and HIV infection was higher in men (6 percent) than in women (1.2 per-
the median survival is approximately 6 months, with most deaths a cent), and among men in the 40- to 59-year-old age group, those newly
result of progressive lymphoma. In one series, poor prognostic features diagnosed with Hodgkin lymphoma had a 14.2 percent chance of being
included an ECOG performance status greater than 2 and ART non- HIV+. Non-Hispanic blacks with newly diagnosed Hodgkin lymphoma
compliance. Promising preclinical data show that treatment with the had a 16.9 percent chance of being HIV+ and Hispanics with newly
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anti-CD30 agent brentuximab vedotin or bortezomib with or without diagnosed Hodgkin lymphoma had a 9.9 percent chance of being HIV+.
vorinostat can decrease growth of primary effusion lymphoma cell Unlike NHL, the incidence of Hodgkin lymphoma is comparable in the
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lines and prolong survival in a mouse xenograft model. pre- and post-ART era. The pathology of Hodgkin lymphoma in HIV+
cases differs from that of HIV– cases, with a higher percent of HIV+
Prognosis patients having a more aggressive histology (mixed cellularity or lym-
As ART improves, the prognosis for patients with HIV-associated NHL phocyte depleted; Table 81–7). An HIV-AIDS cancer match study that
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is defined mainly by lymphoma-related features, and less by HIV. A linked HIV and cancer registry data found that an even higher percent
retrospective review of patients with HIV-associated diffuse large B-cell of patients with HIV-associated Hodgkin lymphoma had mixed cellu-
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lymphoma diagnosed in the pre-ART era (120 patients), and in the ART larity on biopsy (53.7 percent). The Ann Arbor stage at diagnosis is
era (72 patients) showed a median survival of 8 months in the pre-ART higher in HIV+ Hodgkin patients than in HIV– cases, with 41.5 per-
era and 43 months in the ART era; this held true for each of the dif- cent of those with HIV+ Hodgkin lymphoma having stage IV disease
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ferent International Prognostic Index groups. Pooled data for 1546 at presentation, compared to 17 percent of those with HIV– Hodgkin
patients with HIV-associated diffuse large B-cell lymphoma or Burkitt lymphoma (Table 81–7). B symptoms (drenching night sweats, fever,
lymphoma who had been enrolled in phase II or phase III clinical tri- or loss of 10 percent of body weight) are also more common in HIV+
als was evaluated to identify treatment-related factors associated with patients with Hodgkin lymphoma (Table 81–7). 177
overall survival. The use of rituximab was significantly associated with A retrospective study of Adriamycin, bleomycin, vinblastine, and
improved overall survival (hazard ratio 0.55, p <0.001) for patients with dacarbazine (ABVD) chemotherapy in 62 HIV+ patients newly diag-
a CD4 count of greater than 50 cells/μL but not for those patients with nosed with advanced-stage Hodgkin lymphoma showed that ABVD
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CD4 counts of less than 50 cells/μL. A focus on the 1059 patients with and ART could be given safely together. In this study, the median CD4
diffuse large B-cell lymphoma suggested that treatment with EPOCH count at diagnosis was 129 cells/μL, and all patients had stage III or
resulted in a better overall survival (hazard ratio 0.33, p = 0.031) than stage IV Hodgkin lymphoma. Patients received ABVD with filgrastim
treatment with CHOP. On multivariant analysis of R-EPOCH ver- support, as well as trimethoprim-sulfamethoxazole or pentamidine for
sus R-CHOP, the hazard ratio for overall survival was 0.34 favoring P. jiroveci prophylaxis. The overall survival was 76 percent at 5 years,
R-EPOCH, although this did not achieve statistical significance. An with treatment-related mortality of 10 percent. In a large retrospective
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enhanced internal prognostic index based on 650 adults with de novo study of 93 HIV+ patients and 131 HIV– patients with Hodgkin lym-
diffuse large B-cell lymphoma treated at seven National Comprehen- phoma who were treated with ABVD, (HIV+ patients also received con-
sive Cancer Network Cancer Centers in the rituximab era included a comitant ART), those with stage I or II nonbulky disease received four
small portion of HIV+ patients. Patients were risk stratified on an cycles of ABVD plus involved field radiation therapy; the rest received
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8-point scale. Patients with a low score (0 to 1 points) had a 5-year over- six cycles of ABVD with involved field radiation therapy if bulky disease
all survival of 96 percent; patients with a low intermediate score (2 to 3 was present. All patients received prophylaxis for opportunistic infec-
points) had a 5-year overall survival of 82 percent; patients with a high tions. The HIV+ patients had more advanced-stage Hodgkin lymphoma
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intermediate score (4 to 5 points) had a 5-year overall survival of 64 and a worse International Prognostic Score ; despite this the 5-year
percent, and patients with high risk (6 to 8 points) had an overall 5-year overall survival was 81 percent for the HIV+ patients compared to 88
survival of 33 percent. This scale offered better risk stratification than percent for the HIV– patients, a nonsignificant difference. This retro-
the original International Prognostic Index, which was developed in the spective case series demonstrated comparable overall survival in HIV+
prerituximab era. It is recommended that this enhanced International and HIV– patients with Hodgkin lymphoma, and that ART could be
Prognostic Index be used as a guide, in addition to the very robust data given safely with ABVD chemotherapy.
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that patients with CD4 counts of less than 100 cells/μL at the time of The German HIV Related Lymphoma Study Group conducted a
diagnosis of lymphoma have a much worse outcome than those with prospective multicenter study in which HIV+ patients with early stage
higher CD4 counts. favorable Hodgkin lymphoma were treated with two to four cycles of

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