Page 1489 - Hematology_ Basic Principles and Practice ( PDFDrive )

1324 Part VII Hematologic Malignancies

rates, and low overall survival. In a phase III randomized trial in TABLE
Japan, researchers compared two multiagent chemotherapy regimens 83.4 HIV-Associated Lymphoma
(vincristine, cyclophosphamide, doxorubicin [Adriamycin], and
prednisone [VCAP], doxorubicin [Adriamycin], ranimustine, and CD4 Association Other
3
prednisone [AMP], and vindesine, etoposide, carboplatin, and pred- Lymphoma (cells/mm ) EBV Association (%) Cofactors
nisone [VECP] [together, VCAP-AMP-VECP] to cyclophosphamide, PCNSL <50 >95%
hydroxydaunomycin (doxorubicin), Oncovin (vincristine), and pred- DLBCL Variable 40%
62
nisone [together, CHOP-14]) in patients with poor prognosis ATL.
VCAP-AMP-VECP was associated with higher complete response BL >100 30%
rates, with a trend toward improved overall survival, although the HL >100 90%
toxicity of this regimen is significant, and the treatment as planned PEL <100 >75% KSHV
was not tolerated by the majority of patients. In a randomized, phase
II study, patients with newly diagnosed aggressive ATL were treated BL, Burkitt lymphoma; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-
Barr virus; HIV, human immunodeficiency virus; HL, Hodgkin lymphoma;
with VCAP-AMP-VECP with or without the humanized anti–CC KSHV, Kaposi sarcoma–associated herpesvirus; PCNSL, primary central
63
chemokine receptor 4 antibody mogamulizimab. Although patients nervous system lymphoma; PEL, primary effusion lymphoma.
treated with the chemotherapy–antibody combination had higher
complete response rates that were deemed to be clinically significant,
infections, severe skin rashes, and other adverse events were also HIV Hodgkin Lymphoma
more common in the combination arm. Several antivirals used in the
treatment of HIV infection have activity against HTLV-1. Among A 42-year-old human immunodeficiency virus (HIV)–positive patient,
them are zidovudine and lamivudine. The combination of interferon on highly active antiretroviral therapy (HAART) with a CD4 count of
(IFN) and zidovudine has yielded promising results, particularly in 324 cells/mm and undetectable viral load, presents with fever, weight
3
61
the leukemic subtype. Proteasome and histone deacetylase inhibi- loss, and a palpable axillary lymph node. Hodgkin lymphoma (HL) is
tors have attracted interest. Given high CD25 and CD52 expression diagnosed on excisional biopsy, and Epstein-Barr virus (EBV) positivity
in ATL, the efficacy of monoclonal antibodies aimed against these is demonstrated by EBV-encoded RNA (EBER) in the Reed-Sternberg
two receptors has been investigated. Thus far, alemtuzumab, an anti- tumor cells. Although he lacks additional lymphadenopathy, a bone
marrow biopsy is performed, and it shows involvement by HL. He has
CD52 monoclonal antibody, may have some activity in ATL based on stage IVB disease. Pneumocystis jiroveci pneumonia prophylaxis is
small phase II studies and case reports. 64,65 Arsenic trioxide combined started despite an adequate CD4 count in anticipation of chemotherapy.
with IFN-α has been shown to induce remissions in relapsed, refrac- His HAART regimen is reviewed for potential antiviral-chemotherapy
tory patients with ATL, although durable responses were limited. drug interactions. He receives six cycles of full-dose, first-line chemo-
In a trial of 20 patients with ATL, all-trans retinoic acid was used, therapy and achieves a complete remission.
with 40% achieving remission. Allogeneic hematopoietic transplant
has been increasingly recognized as an effective therapy for ATL. 66,67
infected, HIV progression is slowed, and there is less likelihood of
lymphomagenesis.
HIV-ASSOCIATED LYMPHOMAS
Viral Biology and Pathogenesis Epidemiology

+
68
HIV-1 is a retrovirus that infects CD4 T cells and monocytes. It Lymphoma is increased in all HIV risk groups, in contrast to Kaposi
+
69
appears to establish a lifelong reservoir in CD4 T cells. Viral sarcoma, which is rarely seen in injection drug users (or in hemo-
74
infection may lead to cell death or establishment of latency in resting philiacs in an earlier era). There is a well-established relationship
+
cells. HIV infection is spread either through new rounds of virion between CD4 cells per cubic millimeter overall and the risk for
production with cellular infection or cell–cell fusion. There is no lymphoma, but the relationship is complex and differs among lym-
evidence to suggest that infected cells are driven to proliferate. This phomas (see Table 83.4).
is in contrast to HTLV-1 and EBV, where proliferation of infected The incidence of non-Hodgkin lymphoma (NHL) in the HIV
cells appears to play a key role in establishing the long-term viral population, particularly PCNSL (Fig. 83.5A–C), has decreased with
reservoir and perhaps in mediating lymphomagenesis. The lympho- the widespread use of highly active antiretroviral therapy (HAART),
mas that are increased in HIV-infected patients (Table 83.4) are of although patients with HIV on HAART still carry an increased risk
B-cell lineage, and many are associated with EBV, KSHV, or both for lymphoma compared with the HIV-negative population. 75,76 In the
+
(see Table 83.4). HAART era, patients with HIV on average have higher CD4 counts
3
There is no substantial evidence that HIV infection of B cells is (often >100 cells/mm ) when diagnosed with lymphoma as compared
important in the pathogenesis of these lymphomas. Rather, it appears with the pre-HAART era. Among patients with HIV with very low
+
75
that the HIV infection compromises cellular immunity, decreasing CD4 counts, NHLs are still seen at rates similar to the pre-HAART
immune surveillance of EBV- and KSHV-infected B cells. In addi- era. Patients with HIV are now living much longer because of effective
tion, HIV infection stimulates proliferation of B lymphocytes and antiretroviral regimens and decreased rates of opportunistic infection.
70
perhaps genetic aberrations in the proliferating cells. Many possible As a result, malignancy has emerged as the major cause of mortality
mechanisms have been invoked, including (1) direct stimulation of in HIV populations with access to antiretroviral therapy. 77,78
B cells by HIV antigens or antigens associated with opportunistic With the widespread use of HAART, the incidence of HL in
+
infection; (2) stimulation of B cells by cellular proteins (CD40 HIV-seropositive patients has not declined; patients with CD4
3
ligand) incorporated into the HIV virion, leading to expression of counts between 150 and 199 cells/mm actually have higher risk for
+
activation-induced deaminase, an enzyme that mediates double- HIV-associated HL than patients with CD4 counts of less than 50
3 79
stranded DNA breaks; and (3) dysregulation of B cells as a conse- cells/mm .
quence of T-cell dysfunction. 16,70,71
There is also some evidence that host biology may contribute to
lymphomagenesis. In particular, there are a variety of genetic poly- Diagnostic Considerations Specific to Lymphoma in
morphisms that influence susceptibility to HIV-1 infection, such as Patients With HIV
CCR5-Δ32. 72,73 Individuals who are homozygous for this polymor-
phism are much less likely than others to be infected by HIV. Some Lymphomas in patients with HIV infection are more likely to present
evidence has emerged to suggest that, in heterozygotes who are with B symptoms such as fever and night sweats, as well as advanced