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Leukemias, Acute   587


             including lymph nodes, nervous system,   aleukemic or subleukemic patients, evaluation   •  Anemia requiring transfusion
             kidneys, and GI tract.            of the bone marrow is necessary for diagnosis   •  GI toxicosis
  VetBooks.ir   DIAGNOSIS                       ○   Neoplastic cell count ≥ 20% of nucleated   Recommended Monitoring  Diseases and   Disorders
                                               (p. 1068).
                                                                                  •  Tumor lysis syndrome
                                                  cells in bone marrow is diagnostic for AL.
           Diagnostic Overview
                                                  nostic information or direct treatment
           Immature neoplastic cells on peripheral blood   ○   No studies are available to provide prog-  •  Physical  exam  and  CBC:  q  1-2  weeks,
                                                                                    more  frequently  during  induction  period;
           smears or increased numbers on bone marrow   based on bone marrow cytology results.  to monitor remission and myelosuppression
           smears suggest a diagnosis of AL or stage V   ○   Phenotyping is performed on bone   •  Serum chemistry profile, urinalysis: 1 month
           lymphoma.  ALL, AML,  and lymphoma are   marrow  aspirates  with  flow  cytom-  after starting therapy, then at least q 3-4
           typically differentiated by immunophenotyping   etry and on core biopsy samples with   months: more frequently if indicated
           with flow cytometry. In the future, cytogenetic   immunohistochemistry.
           and molecular genetic/epigenetic analysis will                          PROGNOSIS & OUTCOME
           allow more accurate classification and prognos-   TREATMENT
           tication of AL. Mutations in genes associated                          Prognosis is poor for AL. Most patients are ill at
           with development of cancer have been identified   Treatment Overview   diagnosis, and survival times without treatment
           in canine ALL and AML.              Goal is to eradicate leukemic cells with chemo-  are 0-4 weeks. Because ALs are uncommon and
                                               therapy. Supporting the patient until normal   many patients are euthanized at diagnosis, there
           Differential Diagnosis              hematopoiesis resumes is critical. ALL can   is limited information describing treatment
           •  ALL versus  AML:  it is extremely difficult   respond  to  chemotherapy  for  short  periods;   outcomes.
             to distinguish ALL from AML based on   AML is less responsive. Consultation with a   •  CD34 (stem cell marker): in dogs, expression
             morphology (i.e., cytology).      veterinary oncologist is strongly suggested.  supports diagnosis of AL; possibly associated
           •  Available diagnostics do not allow typing of                          with poorer prognosis (median survival, 16
             all ALs. ALs that do not express recognized   Acute General Treatment  days;  range,  3-128  days).  CD34  is  also
             markers are classified as acute undifferentiated   •  Intensive supportive care is important.  expressed in some canine lymphomas.
             leukemias (AUL). It is not always possible to   ○   Broad-spectrum antibiotic therapy for   •  ALL:  no  available  prognostic  information
             distinguish ALL from stage V lymphoma.  treating/preventing secondary infections   for cats in post-FeLV era. Historically, 65%
           •  Stage V lymphoma                    with severe neutropenia (prophylaxis not   response rate for median of 7 months. Infor-
           •  Ehrlichiosis                        required in cats)                 mation about prognosis in dogs confounded
                                                ○   Intravenous fluid therapy       by difficulty distinguishing ALL from stage
           Initial Database                     ○   Peripheral veins for venipuncture/catheter   V lymphoma and treatment with a variety
           •  CBC/blood smear: leukocytosis with blasts   placement if severe thrombocytopenia  of  protocols;  30%-65%  respond,  with  an
             and cytopenias. Nonregenerative anemia   ○   Transfusions (p. 1169)    average survival of days to 4 months. With
             and thrombocytopenia common and may   ○   Nutritional support          CHOP-based protocols, 85% respond, with
             be severe. Neutropenia is more common,   •  Chemotherapy: hospitalization for supportive   a remission duration 16-218 days (median,
             but neutrophilia is possible. Aleukemic   care during induction period is indicated.   41 days).
                                                                                         +
             or subleukemic patients have low-normal   Clinically significant myelosuppression is   ○   CD8  (cytotoxic  T-cell) lymphocytosis
             white blood cell (WBC) count with no or   expected due to myelophthisis. Appropri-  (dog):  abnormal  cell  counts  > 30,000/
             some circulating immature neoplastic cells,   ate safety precautions must be taken when   mcL associated with shorter survival (131
             respectively.                      handling antineoplastic drugs.        vs. 1098 days).*
                                                                                          +
           •  Flow  cytometry  is  the  primary  diagnostic   ○   Consultation with referral to an oncolo-  ○   CD21  (B-cell) lymphocytosis with large
             for confirming and classifying AL. Flow   gist is recommended due to the need for   cells (dog): median survival of 129 days*
             cytometry counts and immunophenotypes   intensive support, risk of severe adverse   ○   This study(*) included dogs with stage V
             neoplastic cells. Blood in EDTA should be   effects, and for AML, the requirement for   lymphoma, CLL, and ALL.
             submitted for this test if blasts seen on CBC.   intense chemotherapy protocols that are   •  AML: a few cases surviving 3-4 months have
             Because cells must be alive, samples must   not routine.               been reported.  Treatments have minimal
             arrive at lab within 24-48 hours.  ○   ALL:  L-CHOP  (L- asparaginase, cyclo-  effect on the course of the disease, and
           •  Polymerase chain reaction (PCR) for antigen   phosphamide,  hydroxydaunorubicin  prognosis is grave.
             receptor rearrangement (PARR) identifies   [doxorubicin], Oncovin [vincristine],
             clonal expression of genes for lymphoid   and prednisone)–based chemotherapy    PEARLS & CONSIDERATIONS
             receptors using blood or bone marrow smears.   protocols (p. 602). Radiation has been
             A recent study showed AML in dogs is fre-  used  for  central  nervous  system  (CNS)   Comments
             quently associated with clonal rearrangements   involvement; prednisone for palliative care  •  Cytologic  exam  of  a  blood  smear  is
             of lymphoid receptors, so this test is not useful   ○   AML:  protocols  not  well  defined  and   imperative if leukocytosis or cytopenias on
             for differentiating ALLs from AMLs.  results are disappointing. First-line therapy   CBC.
           •  Serum chemistry profile and urinalysis  is cytosine arabinoside and doxorubicin;   •  Patients with AL present with nonspecific
           •  FeLV/feline immunodeficiency virus ELISA   anecdotal responses to L-asparaginase plus   signs. Cytologic evaluation of peripheral
             test (cats) ± FeLV PCR using bone marrow   corticosteroid              blood and bone marrow smears diagnoses AL,
             (p. 1342).                         ○   Bone marrow/stem cell transplantation   but flow cytometry is needed to differentiate
           •  Ehrlichia serology, if indicated (p. 285)  limited by short remission times and   ALL, AML, and stage V lymphoma. Because
           •  Diagnostic imaging (for staging): thoracic   difficulty identifying a suitable donor  ALs progress rapidly, consultation with an
             radiography, abdominal ultrasonography                                 oncologist should be pursued quickly and
           •  ± Cytology of enlarged  lymph nodes  or   Chronic Treatment           emergency referral considered.
             organs: to detect infiltration    Patients responding to treatment receive   •  Owners  should  be  advised  of  the  poor
                                               chemotherapy for the remainder of their lives.  prognosis and potential for adverse effects
           Advanced or Confirmatory Testing                                         with  treatment  of  AL.  Supportive  care  is
           Bone marrow aspiration or core biopsy is used   Possible Complications   needed.
           for evaluation of cell morphology, percentage of   •  Myelosuppression:  neutropenia,  thrombo-  •  Better characterization of AL and develop-
           neoplastic cells, and evaluation of cell lines. For   cytopenia          ment of novel treatments targeting the
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