Page 761 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 739

Polycythemia Vera lymphoid or myeloid. 751 Dogs with blast crisis have a poor progno-
In treating PV, therapy is directed at reducing RBC mass. The sis, despite rescue with more aggressive multiagent chemotherapy.
PCV should be reduced to 50% to 60% or by one-sixth of its
VetBooks.ir starting value. Phlebotomies should be performed as needed, Essential Thrombocythemia
Few cases have been reported, but one dog was treated success-
administering appropriate colloid and crystalloid solutions to
replace lost electrolytes; 20 mL of whole blood/kg of body weight fully with a combination chemotherapy protocol that included
can be removed at regular intervals. 687 In humans, phlebotomy vincristine, Ara-C, cyclophosphamide, and prednisone. 714 Treat-
continues to be the therapeutic approach used most frequently. ment is controversial in humans because of the lack of evidence
The chemotherapeutic drug of choice is hydroxyurea, an inhib- that asymptomatic patients benefit from chemotherapy. Patients
itor of DNA synthesis. This drug should be administered at an with thrombosis or bleeding are given cytoreductive therapy.
initial dose of 30 mg/kg for 10 days and then reduced to 15 mg/ Hydroxyurea is the drug of choice for initially controlling the
kg PO daily. 690 The major goal of treatment is to maintain the thrombocytosis. 710 JAK2 small molecule inhibitors have been
PCV as close to normal as possible. Radiophosphorus ( P) has used in people with ET, 680 and although no studies have investi-
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been shown to provide long-term control in people with PV and gated JAK2 mutations in dogs with ET, one could speculate on the
ET but has seen only limited use in veterinary medicine. 747,748 A use of oclacitinib (Apoquel) in dogs. Radiophosphorus treatment
JAK2 inhibitor, ruxolitinib (Jakafi), has been approved for second- is also occasionally used in people with ET. 747
line use in people with PV. 680 A mutation in the JAK2 gene that
is identical to that observed in people was documented in one of Myelodysplastic Syndrome
five dogs with PV 681 ; therefore one could speculate that oclaci- There is no standard therapeutic regime for MDS. Often, humans
tinib (Apoquel), which has some JAK2 inhibitory activity and is receive no treatment if the cytopenias do not cause clinical signs.
FDA-approved for use in dogs with atopy, could have therapeu- Transfusions are given when necessary, and patients with fever
tic potential for PV in some dogs. This potential application for are evaluated aggressively to detect infections. Growth factors,
oclacitinib has not, as yet, been investigated. such as EPO, GM-CSF, G-CSF, and IL-3, are sometimes used in
patients who require frequent transfusions to increase their blood
Chronic Myelogenous Leukemia cell counts and enhance neutrophil function. 752,753 In one case
It has now been documented that a subset of CML in dogs is report, human EPO was administered (100 U/kg SQ q48 hours)
associated with a BCR–ABL chromosomal abnormality (“Raleigh to a dog with MDS because of profound anemia. The rationale
chromosome”) similar to the “Philadelphia chromosome” translo- for use of EPO was to promote terminal differentiation of dys-
cation responsible for a large majority of CML in humans. Ima- plastic erythrocytes. Human recombinant EPO should be used
tinib mesylate (Gleevec), a tyrosine kinase inhibitor, is known to with caution in animals, as anti-EPO antibodies may be induced
be an effective therapy for CML in humans. For dogs with CML and target endogenous EPO. The PCV increased from 12% to
that have the Raleigh chromosomal abnormality, it is intuitive 34% by day 19 of EPO treatment. This dog remained in remission
that these types of drugs may have activity, and indeed tyrosine for more than 30 months. 638 Other factors that induce differen-
kinase inhibitors have been investigated in dogs with BCR–ABL tiation of hematopoietic cells include retinoic acid analogs, 1,25
translocation CML. 701 One dog with chronic monocytic leukemia dihydroxyvitamin D3, interferon-α, and conventional chemo-
treated with toceranib (Palladia) and prednisone therapy achieved therapeutic agents, such as 6-thioguanine and Ara-C. 754–756 The
a clinical remission (before developing progressive disease) and a propensity of these factors to enhance progression to leukemia is
partial cytogenetic response. In addition, molecular techniques not known in many cases, but the potential risk exists.
may be used to monitor cytogenetic aberrations, such as DNA
copy number aberrations and BCR–ABL translocations, after Prognosis
treatment to gauge the cytogenetic response to therapy. 627,701 The
author (DMV) and others have anecdotally used toceranib and/ In general, the prognosis for animals with MPN is better than for
or imatinib in a handful of CML cases with responses that have dogs with AML, in which it is grave. The prognosis for PV and
lasted several months; the true activity and durability of response CML is guarded, but significant remissions have been achieved
with these agents in dogs awaits further investigation. with certain therapeutic regimes and careful monitoring. Animals
CML has also been managed with chemotherapy to control the commonly survive a year or more. 696,714
proliferation of the abnormal cell line and improve the quality of
life. Hydroxyurea is the most effective agent for treating CML dur- SECTION D: MYELOMA-RELATED DISORDERS
ing the chronic phase. 627,696,749 The initial dosage is 20 to 25 mg/kg
twice daily. Treatment with hydroxyurea should continue until the
leukocyte count falls to 15,000 to 20,000 cells/μL. 694,696,705 Then DAVID M. VAIL
the dosage of hydroxyurea can be reduced by 50% on a daily basis
or to 50 mg/kg given biweekly or triweekly. In humans, the alkyl- Myeloma-related disorders (MRDs) arise when a cell of the
ating agent busulfan can be used as an alternative. 750 An effective plasma cell or immunoglobulin-producing B-lymphocyte pre-
dosage has not been established in the dog, but following human cursor lineage transforms and proliferates to form a clonal neo-
protocols, 0.1 mg/kg/day PO is given until the leukocyte count is plastic population of similar cells. This population is believed in
reduced to 15,000 to 20,000 cells/μL. Vincristine and prednisone most instances to be monoclonal (i.e., derived from a single cell)
therapy resulted in a short remission in one dog with CML. 627 because they typically produce homogeneous immunoglobulin,
Despite response to chemotherapy and control for many months, although some examples of biclonal and polyclonal MRD neo-
most dogs with CML will eventually enter a terminal phase of plasms exist. A wide variety of clinical syndromes are represented
their disease. In one study of seven dogs with CML, 4 dogs under- by MRDs, including multiple myeloma (MM), extramedullary
went terminal phase blast crisis. 696 In humans, blast crisis may be plasmacytoma (EMP [both cutaneous and noncutaneous]), IgM