Page 760 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition
P. 760

738   PART IV    Specific Malignancies in the Small Animal Patient


         sometimes appears disorderly, and there may be variation in the   morphology (especially shape), and leukoerythroblastosis. Bone
         size and shape of neutrophils at the same level of maturation. In   marrow aspiration is usually unsuccessful, resulting in a “dry tap.”
                                                               This necessitates a bone marrow biopsy obtained with a Jamshidi
         addition, neoplastic leukocytes may disintegrate more rapidly and
  VetBooks.ir  appear vacuolated. 697  Because of the invasive nature of CML,   needle. 740  The specimen is processed for routine histopathologic
                                                               examination and, if necessary, special stains for fibrous tissue can
         biopsy of liver or spleen may also help distinguish true leukemia
         from a leukemoid reaction, assuming the animal can tolerate the   be used. Because myelofibrosis occurs secondary to other dis-
         procedure. Fluorescent in situ hybridization analysis is available   eases of bone marrow, such as chronic hemolytic anemia or bone
         to identify chromosomal rearrangements, including translocations   marrow necrosis, the clinician should look for a primary disease
         (e.g., Raleigh chromosome), inversions, and deletions, in dogs;   process.
         some of these aberrations are associated with certain forms of leu-  The concept of clinical staging of patients with AML, MPD,
         kemia, and continued investigations will likely yield a larger data-  and MDS is obviously much different than that of patients with
         base of cytogenetic abnormalities and their links to hematologic   solid tumors. As these hematologic tumors are “liquid,” that is
         malignancies. 614,624–630,678,679,681,699–702         they involve primarily the peripheral blood and bone marrow
            Basophilic leukemia is diagnosed by finding excessive num-  compartments, clinical staging is generally not performed beyond
         bers of basophils in circulation and in bone marrow. Basophilic   these two compartments. Certainly, infiltration of peripheral
         leukemia must be differentiated from mastocytosis based on the   nodes and other organs occurs; however, documentation of their
         morphology of the cell type present. Basophils have a segmented   involvement with advanced imaging or tissue aspirates does not
         “ribbon-like” nucleus and variably sized granules, whereas mast   alter treatment or prognosis in any significant way. Two studies
         cells have a round-to-oval nucleus that may be partially or totally   have documented the proof-of-concept use of 3-T body MRI to
         obscured by small, round, metachromatic-staining granules. This   distinguish diffuse versus focal bone marrow and/or parenchymal
         distinction is usually easy to make; however, in basophilic leuke-  involvement of hematopoetic neoplasia; however, the clinical util-
         mia, changes in the morphology of the nucleus and granules make   ity of this methodology is currently unknown. 741,742  
         the distinction less clear. 706
            ET has been diagnosed based on finding persistent and exces-  Treatment
         sive thrombocytosis (>600,000/μL) without circulating blast cells
         and in the absence of another MPD (e.g., PV), myelofibrosis, or   Acute Myeloid Leukemia
         disorders known to cause secondary thrombocytosis, 710  includ-  Treatment of acute nonlymphocytic leukemias has been unre-
         ing iron deficiency anemia, chronic inflammatory diseases, recov-  warding to date. There is limited information on the response
         ery  from severe hemorrhage,  rebound  from immune-mediated   of specific subtypes of leukemia to uniform chemotherapeutic
         thrombocytopenia,  and absence of a spleen. Thrombocytosis is   protocols, in part owing to the rarity of these diseases and the
         transient in these disorders or abates with resolution of the pri-  paucity of cases in the literature. Veterinarians are advised to
         mary disease. In ET, platelet morphology may be abnormal with   contact a veterinary oncologist for discussion of new protocols
         bizarre giant forms and abnormal granulation. 713  In the bone   and appropriate management of these cases, as novel agents
         marrow, megakaryocytic hyperplasia  is a consistent feature and   are currently in development and may become available in the
         dysplastic changes may be evident in megakaryocytes. 712  Spurious   future.
         hyperkalemia may be present in serum samples from dogs with   The overriding therapeutic goal is to eradicate leukemic cells
         thrombocytosis from any cause due to the release of potassium   and  reestablish  normal  hematopoiesis.  Currently,  this  is  best
         from platelets during clot formation. 738  Measuring potassium in   accomplished by cytoreductive chemotherapy and the agents most
         plasma is recommended in these cases and usually demonstrates a   commonly utilized include combinations of anthracyclines, such
         potassium concentration within reference interval. Platelet aggre-  as doxorubicin, cyclophosphamide, vincristine, 6-thioguanine,
         gability has been variably reported as impaired 713  or enhanced. 712    and prednisone. 618–620,640,644,646,707,743–746  In dogs, cytosine arabi-
         In the one dog in which it was measured, plasma thrombopoietin   noside (Ara-C), 100 to 200 mg/m , given by slow infusion (12–24
                                                                                         2
         (TPO) concentration was normal. 711  It is unclear whether TPO   hours) daily for 3 days and repeated weekly, has been used, as well
         plays a role in ET or is suppressed by the high platelet mass.  as several other variations using subcutaneous injections of Ara-C
            In MDS, abnormalities in two or three cell lines are usually   (see  Chapter 12). Several variations of CHOP- or COP-based
         manifested in peripheral blood as neutropenia with or without a left   protocols (see Section A of this chapter), with or without Ara-C,
         shift, nonregenerative anemia, or thrombocytopenia. Other changes   have been used as well. The overall prognosis with currently avail-
         include macrocytosis and metarubricytosis. The bone marrow is typi-  able treatment is poor. Although response rates to multiagent pro-
         cally normocellular or hypercellular with an increased M : E ratio, and   tocols are relatively high (50%–70%), responses are not durable
         blasts cells, although increased, constitute less than 20% of nucleated   and MSTs, despite aggressive protocols, are generally 0.5 to 2.0
         cells; in a report of 13 dogs with primary or secondary MDS, in all   months. 618–620  Obviously, effective therapies for AML in dogs
         but one dog the blast cell percentage was less than 20%. 739  Dys-  await further investigation.
         plastic changes can be detected in any cell line. Dyserythropoiesis is   Regardless of the chemotherapy protocol used, significant cyto-
         characterized by asynchronous maturation of erythroid cells typified   penias either persist or are sequela to chemotherapy, and intensive
         by large hemoglobinized cells with immature nuclei (megaloblastic   supportive care will be necessary. Transfusions of whole blood or
         change). If the erythroid component is dominant, the MDS is called   platelet-rich plasma may be required to treat anemia and throm-
         MDS-Er (see Table 33.13). 615,638  In dysgranulopoiesis, giant neu-  bocytopenia, and infection should be managed with aggressive
         trophil precursors and abnormalities in nuclear segmentation and   antibiotic therapy. Because of the generally poor response, many
         cytoplasmic granulation can be seen. Finally, dysthrombopoiesis is   clients will choose palliative supportive care; however, the acute
         characterized by giant platelets and micromegakaryocytes.  progression of disease does not allow for prolonged palliation in
            Myelofibrosis should be suspected in animals with nonregen-  most cases and MSTs with supportive care are generally only 1 to
         erative anemia or pancytopenia, abnormalities in erythrocyte   2 weeks. 
   755   756   757   758   759   760   761   762   763   764   765