Page 1493 - Hematology_ Basic Principles and Practice ( PDFDrive )

1328 Part VII Hematologic Malignancies

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liver and salivary glands, as well as the spleen. Unusual presenta- mas, standard antiviral drugs do not have a role in treatment. There
tions of low-grade HCV-associated lymphomas have been described, are several exceptions, however, and these are worth highlighting.
including subcutaneous “lipoma-like” MALT lymphoma predomi- Antiviral therapy for HCV-associated splenic lymphoma with villous
123
nantly in elderly, HCV-positive women. An HCV prognostic score, lymphocytes is accepted as a standard approach and likely has a role
comprised of poor performance status, hypoalbuminemia, and high in the treatment of other HCV-associated indolent lymphomas.
HCV-RNA viral load, effectively risk stratified patients into three Similarly, ganciclovir or valganciclovir appears to have a role in the
groups with significantly different progression-free and overall sur- management of MCD associated with KSHV in patients with HIV.
vival outcomes. 124 Of course, in addition, there is an established role for antiretroviral
therapy in the treatment of patients with HIV patients and malig-
nancy. There are virus-targeted therapies that are broadly accepted as
Therapy standard, including adoptive immunotherapy with EBV-specific T
cells for PTLD. The use of targeted T cells also has promise in other
In patients with indolent lymphomas and untreated HCV infection, settings, including EBV-associated HL. Other virus-targeted therapies
antiviral treatment with pegylated IFN-α and ribavirin may obviate are being developed. Some involve vaccination; others involve induc-
the need for cytotoxic chemotherapy and should be considered as an tion of viral genes in tumor cells, rendering them more susceptible
initial therapeutic strategy. Tumor regression with antiviral therapy to pharmacologic treatment. Finally, it may ultimately be possible to
was first reported in 2002 and is now further supported by subsequent prevent some kinds of lymphoma by preventing viral infection or
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reports. In a recent cohort study from Italy, antiviral treatment altering the host response to viral infection.
resulting in virologic response was shown to be effective as first-line
treatment for indolent HCV-associated lymphomas, with not only
high overall response rates but also a survival advantage on multivari- SUGGESTED READINGS
125
ate analysis. Since 2011, new antiviral agents have become avail-
able, notably protease inhibitors specific for the HCV protease. Balsalobre P, Diez-Martin JL, Re A, et al: Autologous stem-cell transplanta-
Likelihood of response to older therapy is a function of viral genotype, tion in patients with HIV-related lymphoma. J Clin Oncol 27:2192, 2009.
host genetics (IL28R polymorphisms play a critical role in response Barta SK, Lee JY, Kaplan LD, et al: Pooled analysis of AIDS malignancy
to protease inhibitors), and other factors. The field is rapidly evolving, consortium trials evaluating rituximab plus CHOP or infusional EPOCH
and colleagues with specific expertise in appropriate antiviral chemotherapy in HIV-associated non-Hodgkin lymphoma. Cancer
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approaches should be consulted. In general, treatment of the 118:3977, 2012.
underlying HCV is favored in chronically infected patients who Bazarbachi A, Suarez F, Fields P, et al: How I treat adult T-cell leukemia/
develop indolent lymphoma, given the potential for tumor regression lymphoma. Blood 118:1736, 2011.
with antiviral therapy, as well as the theoretical reduction in relapse Bower M, Newsom-Davis T, Naresh K, et al: Clinical features and outcome
that might accompany virologic responses. in HIV-associated multicentric Castleman’s disease. J Clin Oncol 29:2481,
Rituximab has posed an interesting dilemma for the treatment of 2011.
patients with HCV and lymphoma. It has been reported that HCV Carbone A, Cesarman E, Spina M, et al: HIV-associated lymphomas and
plasma RNA increases following rituximab treatment, and there is gamma-herpesviruses. Blood 113:1213, 2009.
certainly the possibility that elimination of B cells for 3–18 months Choi I, Tanosaki R, Uike N, et al: Long-term outcomes after hematopoietic
following treatment may compromise humoral responses to the SCT for adult T-cell leukemia/lymphoma: results of prospective trials.
evolution of HCV quasispecies. However, in studies to date, overall Bone Marrow Transplant 46:116, 2011.
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survival is not inferior. Similarly, combination chemotherapy is safe Chuang SS, Liao YL, Chang ST, et al: Hepatitis C virus infection is sig-
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in patients with HCV infection. Rituximab does not seem to nificantly associated with malignant lymphoma in Taiwan, particularly
increase the risk of hepatotoxicity with anthracycline-based chemo- with nodal and splenic marginal zone lymphomas. J Clin Pathol 63:595,
124
therapy regimens. Rituximab is specifically recommended for the 2010.
treatment of HCV-associated cryoglobulinemia (although, as in the Engels EA, Pfeiffer RM, Landgren O, et al: Immunologic and virologic
treatment of Waldenström macroglobulinemia, it must be appreci- predictors of AIDS-related non-Hodgkin lymphoma in the highly
ated that the initial response to rituximab may be an increase in the active antiretroviral therapy era. J Acquir Immune Defic Syndr 54:78,
IgM paraprotein level, necessitating plasmapheresis). Unlike in cases 2010.
of indolent lymphoma, where antiviral therapy alone may be suffi- Epeldegui M, Hung YP, McQuay A, et al: Infection of human B cells with
cient, rituximab-containing multiagent chemotherapy regimens are Epstein-Barr virus results in the expression of somatic hypermutation-
recommended for HCV-associated DLBCL, and attempts to con- inducing molecules and in the accrual of oncogene mutations. Mol
comitantly treat with antivirals are generally not advised, given the Immunol 44:934, 2007.
added risks of cytopenias and hepatotoxicity. Evens AM, Roy R, Sterrenberg D, et al: Post-transplantation lymphoprolif-
erative disorders: diagnosis, prognosis, and current approaches to therapy.
Curr Oncol Rep 12:383, 2010.
Aspects of Therapy Giordano TP, Henderson L, Landgren O, et al: Risk of non-Hodgkin lym-
phoma and lymphoproliferative precursor diseases in US veterans with
With regard to the use of rituximab to treat B-cell lymphomas in hepatitis C virus. JAMA 297:2010, 2007.
patients with HCV, overall survival is not inferior, although there do Guech-Ongey M, Simard EP, Anderson WF, et al: AIDS-related Burkitt
appear to be increased rates of hepatotoxicity and rises in HCV viral lymphoma in the United States: what do age and CD4 lymphocyte
load during therapy. Similarly, combination chemotherapy is safe in patterns tell us about etiology and/or biology? Blood 116:5600, 2010.
patients with HCV infection, although HCV RNA levels can rise Heslop HE, Slobod KS, Pule MA, et al: Long-term outcome of EBV-specific
during treatment. Interestingly, patients with HCV and splenic MZL T-cell infusions to prevent or treat EBV-related lymphoproliferative
have had regression of their tumors with treatment for HCV infection disease in transplant recipients. Blood 115:925, 2010.
with IFN-α and ribavirin, an effect not seen in HCV-negative Hishizawa M, Kanda J, Utsunomiya A, et al: Transplantation of allogeneic
patients with splenic MZL treated with the same regimen. hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospec-
tive study. Blood 116:1369, 2010.
Ito M, Kusunoki H, Mochida K, et al: HCV infection and B-cell lymphoma-
FUTURE DIRECTIONS genesis. Adv Hematol 2011:835314, 2011.
Jaffe ES, Campo E, Swerdlow SH, et al: The 2008 WHO classification
In this chapter, a variety of virus-associated lymphomas and lympho- of lymphoid neoplasms and beyond: evolving concepts and practical
proliferative diseases have been reviewed. For most of these lympho- applications. Blood 117:5019, 2011.