Page 1306 - Small Animal Internal Medicine, 6th Edition

1278 PART XII Oncology

TABLE 77.2
VetBooks.ir Modified Veterinary Cooperative Oncology Group – Common Terminology Criteria for Blood Adverse Events (VCOG-
CTCAE) Associated With Chemotherapy (see Supplemental Reading)
GRADE
ADVERSE EVENT 1 2 3 4 5

HGB Dog: 10 G/dL to <LLRI Dog: 8 G/dL -10 G/dL Dog: 6.5 G/dL-8 G/dL Dog: <6.5 G/dL Death
Cat: 8 G/dL to <LLRI Cat: 6.5 G/dL-8 G/dL Cat: 5 G/dL-6.5 G/dL Cat: <5 G/dL Death
HCT or PCV Dog: 30% to <LLRI Dog: 20%-30% Dog:15%-20% Dog: <15% Death
Cat: 25% to <LLRI Cat: 20%-25% Cat: 15%-20% Cat: <15% Death
Neutrophils 1500/µL to >LLRI 1000-1499/µL 500-999/µL <500/µL Death
Platelets 100,000/µL to LLRI 50,000-99,999/µL 25,000-49,999/µL <25,000/µL Death

HCT, Hematocrit; HGB, hemoglobin concentration; LLRI, lower limit of the reference interval; PCV, packed cell volume.
(Courtesy Veterinary Cooperative Oncology Group, 2011.)

occur necessitate the temporary or permanent discontinua- Neutropenia usually constitutes the dose-limiting cytope-
tion of the offending agent or agents. Table 77.1 lists agents nia and occasionally leads to life-threatening sepsis in dogs;
commonly implicated in this type of toxicity. although neutropenia does occur in cats receiving chemo-
It is easy to anticipate the cell line that will be affected on therapy, it rarely leads to the development of clinically rec-
the basis of the bone marrow transit times and circulating ognizable sepsis. The nadir (i.e., lowest point in the curve)
half-lives of blood-formed elements. For example, the bone of neutropenia for most drugs usually occurs 5 to 7 days after
marrow transit time and circulating half-life of red blood treatment, and the neutrophil counts return to normal
cells in the dog are approximately 7 and 70 to 120 days, those within 36 to 72 hours of the nadir. With certain drugs, the
of the platelets are 3 to 5 days and 4 to 6 days, and those of nadir of neutropenia is delayed (i.e., ≈3 weeks for carboplatin
neutrophils are 5 to 6 days and 4 to 8 hours, respectively. On in dogs and cats). Dogs with neutrophil counts less than
the basis of this, neutropenia usually occurs first, followed 2000 cells/µL should be closely monitored for the develop-
by thrombocytopenia. Chemotherapy-induced anemia is ment of sepsis, although overwhelming sepsis rarely occurs
rare in dogs and cats and, if it occurs, is of late onset (3-4 in animals with neutrophil counts of more than 1000 cells/µL.
months after initiation of therapy); in some dogs on chemo- As reported in a recent study, the development of sepsis in
therapy, iron deficiency anemia is due to chronic gastro- neutropenic cats is extremely rare or may go unrecognized.
intestinal bleeding from gastroduodenal ulcers or erosions In this collaborative study from 8 institutions where patients
(see Chapters 30 and 82). Other patient-related factors (e.g., were selected based on the authors’ recall, only 20 cats with
malnutrition, old age, concurrent organ dysfunction, prior febrile neutropenia while undergoing chemotherapy were
extensive chemotherapy) and tumor-related factors (e.g., identified. Most cats had lymphoma and were receiving
bone marrow infiltration, widespread parenchymal organ either lomustine and/or vinca alkaloids (Pierro et al., 2016).
metastases) can also affect the degree of myelosuppression. We have also observed severe, long-lasting myelosuppres-
Although thrombocytopenia is probably as common as sion associated with administration of lomustine in a limited
neutropenia, it is rarely severe enough to cause spontaneous number of cats (Fig. 77.1).
bleeding, and therefore it is not discussed at length here. In The pathogenesis of sepsis in neutropenic animals is as
general, in most dogs with chemotherapy-induced thrombo- follows: First, the chemotherapy-induced death and desqua-
cytopenia, the platelet counts remain above 50,000 cells/µL; mation of gastrointestinal crypt epithelial cells occur simul-
spontaneous bleeding usually does not occur until platelet taneously with myelosuppression; next, enteric bacteria are
counts are below 30,000/µL. Some drugs and protocols are translocated through the damaged mucosal barrier into the
associated with predictable thrombocytopenia, including systemic circulation; and, finally, because the number of neu-
doxorubicin and dacarbazine (ADIC), D-MAC (see the table trophils in the circulation is not sufficient to phagocytose
on cancer chemotherapy protocols in page 1337), lomustine, and kill the invading organisms, multiple organs become
and melphalan in dogs; platelet counts associated with these colonized with the bacteria and death ensues, unless the
protocols can be lower than 50,000/µL. Chemotherapy- animal is treated appropriately.
induced thrombocytopenia is extremely rare in cats; however, It is important to identify the septic neutropenic patient
because platelet clumping is common in cats, pseudothrom- using laboratory means due to the fact that the cardinal signs
bocytopenia (i.e., low platelet “count” but platelet aggregates of inflammation (i.e., redness, swelling, increased tempera-
on the analyzer graphics or blood smear) is seen frequently. ture, pain, abnormal function) may be absent because there
Thrombocytosis is common in cats and dogs receiving vin- are not enough neutrophils to participate in the inflamma-
cristine or corticosteroids. tory process. The same holds true for radiographic changes