Page 733 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 711

lymphoma depends on the extent of disease. Solitary lesions have Proliferative assays such as analysis of bromodeoxyuridine
a better prognosis and may be treated with surgical excision or RT, (BrdU) uptake, Ki67 antibody reactivity, and AgNOR indices to
measure proliferative activity of tumor cells have been shown to
although thorough staging for systemic disease should be undertaken
VetBooks.ir before local therapy and active surveillance for subsequent develop- provide prognostic information in dogs treated with combina-
tion chemotherapy; however, different studies are contradictory
ment of recurrent or systemic involvement should be implemented.
Fractionated RT has been associated with long-term control. 366,367 and the information is rarely helpful clinically. In addition, in one
Diffuse cutaneous lymphoma is best managed with systemic therapy, report, the proportion of tumor cells undergoing apoptosis was
although the rate and durability of response is generally less than in modestly predictive of remission duration. 123,174
multicentric lymphoma. The most widely used protocols for epi- The anatomic site of disease is also of considerable prognostic
theliotropic and nonepitheliotropic cutaneous T-cell lymphoma importance. Primary diffuse cutaneous, diffuse GI, hepatosplenic,
(CTCL) include CCNU (with or without l-asparaginase [see Table and primary CNS lymphomas tend to be associated with a poor
33.6]) along with prednisone, pegylated l-asparaginase (very costly), prognosis. Dogs with indolent cutaneous T-cell lymphocytic infil-
77
and oral retinoic acid analogs (limited availability; acitretin, etretinate, tration experience long-term survivals. Sex has been shown to
isotretinoin). 269,366,368–372 Multiagent protocols (generally CHOP- influence prognosis in some studies. 235,237 Neutered females tend to
based) may also be used, but have generally been instituted after sin- have a better prognosis; male dogs may have a higher incidence of
gle-agent therapies have failed. Although reported response rates can the T-cell phenotype, which may account for the poorer prognosis.
range from 40% to 80%, median remission durations are generally Reported biomarkers of prognosis, summarized in Table 33.8,
short (approximately 3–6 months); occasionally, durable remissions include increased circulating levels of glutathione-S-transferase,
are encountered. Sporadic reports of other therapies for cutaneous thymidine kinase, lactate dehydrogenase, C-reactive proteins,
lymphoma in small numbers of cases include the use of COAP (cyclo- and VEGF. Finally, one report suggests that a history of chronic
phosphamide, vincristine [Oncovin], Ara-C, and prednisone), topical inflammatory disease of several types predicts likelihood of early
mechlorethamine (Mustargen), rabacfosadine, recombinant human relapse. 202,398 These putative prognostic indicators require further
interferon-alpha, and masitinib. 132,269,368,373 All these reports involved confirmation in larger trials.
small numbers of cases and resulted in relatively short response dura- Of particular interest is the capacity of gene expression analysis
tions. Whole-body surface RT has also been explored for the treat- to predict and indeed subcategorize the lymphomas into prognos-
ment of diffuse cutaneous lymphoma in preliminary trials. 348,374 tic categories. 14,20,178,179,384 Although these types of analysis are not
A form of cutaneous lymphocytic infiltration has been char- currently widely available in the veterinary clinical setting, they are
acterized as an indolent T-cell lymphoma based on clonality. It routinely used for prognostication and therapeutic decision making
77
is associated with slow progression and long-term survival after in people and are likely to become more readily available to veteri-
corticosteroid management; however, it does have the potential to nary clinicians in the next decade. The potential of genetic molecular
178
progress to high-grade lymphoma. profiling in veterinary oncology is illustrated by Frant et al : they
were able to subcategorize dogs with peripheral nodal lymphoma into
Prognosis three prognostic categories based on a benchtop quantitative real-time
(qRT)-PCR diagnostic analysis of expression of only four genes. 178
The prognosis for dogs with lymphoma is highly variable and
depends on a wide variety of factors that are documented or The Indolent Lymphomas
presumed to affect response to therapy. Although rarely curable Histologic grade (subtype) greatly influences prognosis. Dogs
(<10% of cases), CRs and a good quality of life during extended with lymphoma classified as intermediate or high grade tend
remissions and survival are typical. Factors that have been shown to respond to chemotherapy, but can relapse early. Dogs with
to influence treatment response and survival for peripheral nodal low-grade indolent lymphomas have a poorer response to che-
lymphoma are summarized in Tables 33.7 and 33.8. The prognos- motherapy, yet have a survival advantage over dogs with inter-
a
tic factors most consistently identified for peripheral nodal lym- mediate- and high-grade lymphomas (see Fig. 33.12). Several
phoma are immunophenotype, WHO substage (see Fig. 33.11B), case compilations have documented that dogs with indolent lym-
and an indolent subclassification (Fig. 33.12). Many reports have phoma (e.g., MZL, MCL, TZL) experience prolonged STs, often
confirmed that dogs with nonindolent intermediate- and high- in the absence of any or aggressive chemotherapy; that is, they
grade T-cell lymphomas have significantly shorter remissions and often enjoy prolonged survival despite intervention rather than
survival durations than dogs with intermediate or high-grade because of intervention. 100–102 One caveat is that canine nodal
B-cell disease. 68,69,112,113,116,277,391 This holds true primarily for marginal zone lymphoma, which is designated as an indolent dis-
dogs with multicentric lymphoma because the immunopheno- order, is generally more aggressive with median progression-free
type of solitary or extranodal forms of lymphoma has not been intervals of 5 months and overall STs of only 8.5 months; this
thoroughly investigated with respect to prognosis. In addition, is substantially less than splenic MZL, which is associated with
it has been shown that dogs with B-cell lymphomas that express long-term survival or cure after splenectomy. 108 Many dogs with
lower than normal levels of B5 antigen (expressed in 95% of non- indolent lymphoma will live near normal life-spans and ultimately
neoplastic lymphocytes) or low levels of class II MHC expression die of non–lymphoma-related disorders. Generally, with the indo-
experience shorter remissions and survival durations. 69,391 Dogs lent lymphomas, unless the presence of disease is having an effect
presented with WHO substage b disease (i.e., clinically ill) also do on the quality of life or results in clinically significant cytopenias
poorly compared with dogs with substage a disease. 68,112,116,235,387 (myelophthisis), active surveillance in the absence of treatment is
Dogs with stage I and II disease have a better prognosis than those recommended. If treatment is deemed necessary, more conserva-
dogs in more advanced stages (stage III, IV, and V). tive protocols (e.g., chlorambucil/prednisone or cyclophospha-
mide/prednisone) are initiated. The goal of therapy is to control
a 108, 111, 123, 139, 177–179, 207, 210, 213, 235, 237, 273, 276–278, 287, the disease (stable disease or partial response) as CRs are unusual
290, 293, 294, 299, 328, 365, 375–397. with the indolent lymphomas.