Page 737 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 715

Treatment of Chronic Lymphocytic Leukemia
been used by the author (DMV) and others for dogs with ALL;
Because of the indolent and often asymptomatic nature of CLL,
however, responses and durability of response are generally disap-
VetBooks.ir the decision to treat is often based on the clinical and laboratory pointing. The standard of care in humans with acute leukemia
findings in the individual dog. Most oncologists recommend
generally involves bone marrow ablative treatments with stem cell
active surveillance (monthly or bimonthly physical examination or marrow replacement, technology that is not widely available or
and CBC) over active therapy when CLL is identified inciden- often pursued in veterinary oncology.
tally, there are no accompanying clinical signs, and other signifi-
cant hematologic abnormalities are not identified. If the dog is Prognosis
significantly anemic or thrombocytopenic or is showing evidence
of significant lymphadenopathy or hepatosplenomegaly, therapy In general, CLL is an indolent disease (with the aforementioned
should be considered. There is no consensus on what degree of exception of atypical CLL), and many dogs will not require ther-
lymphocytosis is used to initiate therapy; the definition of “exces- apy for some time after diagnosis; several dogs have been reported
sively high” varies among oncologists, and a standard has not been to survive a year or more without treatment. 400,414 For those
established in veterinary medicine. The author (DMV) prefers dogs that are treated, normalization of lymphocyte counts can be
to base treatment decisions on the presence of significant consti- expected in 70% of cases. In one report of 17 dogs treated with
tutional signs and peripheral cytopenias rather than an absolute vincristine, chlorambucil, and prednisone, MST was approxi-
lymphocyte count. Currently, the most effective drug available for mately 12 months with an expected 30% survival at 2 years. 405
treatment of CLL, once therapy is deemed necessary, is chloram- In larger compilations of cases that include immunophenotypic
bucil. 400,405 Chlorambucil is given orally at a dose of 0.2 mg/kg analysis, treatment protocols were poorly documented, although
2
or 6 mg/m PO once daily for 7 to 14 days; the dose can then be most received chlorambucil and prednisone. The immunopheno-
reduced to 0.1 mg/kg or 3 mg/m PO daily. For long-term main- type of CLL has been shown to be prognostic; in a report of 43
2
tenance, a dose of 2.0 mg/m every other day can be used. The cases, MSTs of 930 days, 480 days, and 22 days were reported for
2
dose is adjusted based on clinical response and bone marrow toler- T-CLL, B-CLL, and atypical CLL, respectively. 400 In this group
2
ance. Pulse-dose chlorambucil (20–30 mg/m q 2 weeks) has been of dogs, young age and anemia were also associated with a poor
anecdotally used for CLL in some cases; however, no compilations prognosis. In another series with limited treatment information,
+
of cases have been reported to assess effectiveness of this protocol. dogs with CLL of a CD8 immunophenotype that presented
Oral prednisone is used concurrently with chlorambucil at doses with less than 30,000 lymphocytes/μL or greater than 30,000
of 1 mg/kg daily for 1 to 2 weeks, then 0.5 mg/kg every other day lymphocytes/μL had MSTs of 1098 and 131 days, respectively. 400
thereafter. The addition of vincristine or the substitution of cyclo- Prognosis for dogs with ALL is generally very poor. In a study
phosphamide for chlorambucil has been advocated in animals that of 21 dogs treated with vincristine and prednisone, dogs achieving
do not respond to chlorambucil. complete or partial remission (29%) had an MST of 120 days,
Treatment of CLL, once initiated, is primarily palliative with and few dogs survived longer than 8 months. 408 In one report of
rare complete remissions and a uniformly fatal course. Owing to 46 cases of ALL with a CD34 phenotype, dogs had a MST of
+
the indolent nature of this disease, however, STs have been in the 16 days (range, 3–128 days), even though the majority received a
range of 1 to 3 years with a good quality of life. 400,405,410 The CHOP-based treatment protocol. 394 In addition, dogs with B-cell
phenotype of CLL is usually stable over months to years; however, ALL (CD21 ) in which the lymphocytes were large cells (forward
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the disease may evolve into an acute phase, and some dogs will scatter lymphocyte/forward scatter neutrophil ratio of greater than
develop a form of lymphoma that is rapidly progressive and char- 0.58 by flow cytometric analysis) had a MST of only 129 days,
acterized by the presence of pleomorphic large lymphocytes 411,412 ; independent of treatment protocol. 394
in humans, this is termed Richter’s syndrome. 413 Based on a data set
of 153 cases, 2% of T-CLLs and 10% of B-CLLs progressed to a
Richter-like acute disease often characterized by lymphadenopa- SECTION B: FELINE LYMPHOMA AND
thy, coughing, vomiting, weight loss, and neurologic signs. 412 In LEUKEMIA
these eight dogs, the progression to acute disease occurred 2 to
16 months after initial diagnosis of their CLL and MST after this
progression was only 41 days despite aggressive (CHOP-based) DAVID M. VAIL AND MARIE PINKERTON
chemotherapy in half of the cases. 412
Lymphoma
Treatment of Acute Lymphocytic Leukemia
Lymphoma (malignant lymphoma or lymphosarcoma) comprises
Much of the morbidity in dogs with ALL results from effacement a diverse group of neoplasms that have in common their origin
of bone marrow (myelophthisis) and subsequent life-threatening from lymphocytes. The neoplasms usually arise in lymphoid tis-
peripheral cytopenias. Neutropenia, thrombocytopenia, and ane- sues such as lymph nodes, spleen, and bone marrow; however,
mia may be severe. Dogs often require supportive therapy, such as they may arise in almost any tissue in the body. Lymphoma is one
fresh whole-blood transfusions, broad-spectrum antibiotics, fluid of the most common neoplasms seen in the cat. See Box 33.4.
therapy, and nutritional support. Careful monitoring for sepsis,
hemorrhage, and DIC is important. Specific treatment of ALL Incidence
would require aggressive chemotherapy; however, consistently
efficacious protocols have not been developed in veterinary medi- Epidemiologic reports before 1990 suggested that lymphoma
cine, and there are few published reports. CHOP-based proto- accounted for 50% to 90% of all hematopoietic tumors in the
cols, similar to those used for lymphoma (see Table 33.4), have cat, 421,422 and because hematopoietic tumors (lymphoid and