Chemotherapeutic Treatment for Leukemia in a Bearded
Dragon (Pogona vitticeps)
Authors: Gwen Jankowski, Jeffrey Sirninger, Jessica Borne, and Javier G.
Nevarez
Source: Journal of Zoo and Wildlife Medicine, 42(2) : 322-325
Published By: American Association of Zoo Veterinarians
URL: https://doi.org/10.1638/2010-0150.1
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Journal of Zoo and Wildlife Medicine 42(2): 322–325, 2011
Copyright 2011 by American Association of Zoo Veterinarians
CHEMOTHERAPEUTIC TREATMENT FOR LEUKEMIA IN A
BEARDED DRAGON (POGONA VITTICEPS)
Gwen Jankowski, D.V.M., Jeffrey Sirninger, D.V.M., Ph.D., Dipl. A.C.V.P., Jessica Borne, D.V.M., and
Javier G. Nevarez, D.V.M., Ph.D.
Abstract: A 4.5-yr-old, captive-bred, male bearded dragon (Pogona vitticeps) presented for lethargy, anorexia,
and increased mucoid salivation with upper respiratory clicks. Diagnostics were declined and the bearded dragon
was prescribed ceftazidime 20 mg/kg i.m. q 72 hr. The patient presented again 1 wk later with a marked
monocytosis, heterophilia, and lymphocytosis, and a clinical diagnosis of chronic monocytic leukemia was made.
Chemotherapy with cytosine arabinoside (100 mg/m2 over 48 hr i.v.) was initiated. Forty-four hours into the
treatment the dragon became acutely unresponsive and died within 1 hr. Adverse effects as a result of i.v. cytosine
arabinoside therapy were not identified despite previous reports suggestive that the drug induces renal failure.
Key words: Bearded dragon, chemotherapy, cytosine arabinoside, leukemia, neoplasia, Pogona vitticeps.
BRIEF COMMUNICATION
A 4.5-yr-old, captive-bred, male bearded dragon (Pogona vitticeps) presented with lethargy,
anorexia, weight loss, and increased mucoid
salivation with occasional respiratory clicks. The
dragon had lost 122 g over the previous year,
weighing 348 g upon presentation. Husbandry
was considered good to excellent. Physical examination revealed 5% dehydration, mucoid respiratory discharge, and upper respiratory noise. The
owner declined diagnostics and elected to treat
empirically. The dragon was given intracoelomic
fluids and discharged with instructions to give
ceftazidime (20 mg/kg i.m. q 72 hr; Fortaz,
GlaxoSmithKline, Brentford, Middlesex TW8
9GS, United Kingdom) and soak the dragon in
warm water twice daily.
The patient presented 1 wk later for regurgitation and diarrhea along with the previously
described clinical signs, and was hospitalized. It
was dehydrated (8%) and lethargic, and had been
anorexic for over 2 wk. The owner had been
occasionally soaking the animal in warm water
and force-feeding insects and oatmeal. Radiographs showed a severely distended colon, and
fecal floatation was positive for pinworms (Oxyuris spp). Complete blood count (CBC) and
chemistry revealed anemia (hematocrit: 18%;
From the College of Veterinary Medicine at the
University of Illinois, 1008 West Hazelwood Drive,
Urbana, Illinois 61802, USA (Jankowski); and the Louisiana State University School of Veterinary Medicine, Skip
Bertman Road, Baton Rouge, Louisiana 70803, USA
(Sirninger, Borne, Nevarez). Present address (Jankowski):
Lincoln Park Zoo, 2001 North Clark Drive, Chicago,
Illinois 60614, USA. Correspondence should be directed to
Dr. Jankowski (gwen.jankowski@gmail.com).
reference range: 24.4–34.6),8 and hyperglycemia
(.1,100 g/dl; reference range 172–242).8 A severe
leukocytosis (322 3 103 cells/ll;reference range:
5.5–13.3 3 103)8 characterized by a heterophilia
(48.4 3 103 cells/ll; reference range: 1.7–4.5 3
103),8 lymphocytosis (29 3 103 cells/ll; reference
range: 1–9 3 103),8 and marked monocytosis (243.5
3 103 cells/ll; reference range: 0.09–0.25 3 103)8
led to presumptive diagnosis of chronic monocytic leukemia. Several mitotic figures were noted on
the blood smear. The prolific cell line was
determined to be monocytic, based upon the
presence of multiple concurrent phenotypic criteria typical for mature monocytes, including moderate size; lightly basophilic cytoplasm; low to
moderate nuclear-to-cytoplasmic ratios; pleomorphic nuclear shape (round, oval, reniform, or
lobated, but nonsegmented); frequent occurrence
of moderate numbers of variably sized, welldelimited, clear cytoplasmic vacuoles; and euchromatic chromatin patterns without distinct
nucleolar rings (Fig. 1). A hematologic diagnosis
of leukemia was based on the presence of the
profound monocytosis and mitotic figures in cells
with similar cytoplasmic features.
Initial therapy included i.v. Normosol R (20
ml/kg/day; Hospira Inc., Lake Forest, Illinois
60045, USA), ceftazidime 20 mg/kg i.m. q 72 hr,
warm water enemas, and tube-feeding with Critical Care (Oxbow Animal Health, Murdock,
Nebraska 68407, USA) every 48 hr. One dose of
ivermectin (0.2 mg/kg i.m.; Ivomec, Merial,
London, CM19 5TG United Kingdom) was given
to treat the pinworm infection. The lizard improved clinically with supportive care and its
weight increased to 418 g. A CBC several days
after hospitalization showed a leukocytosis of 420
3 103 cells/ll characterized by 304.5 3 103
322
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JANKOWSKI ET AL.—TREATMENT OF LEUKEMIA IN A BEARDED DRAGON
323
Figure 1. A blood smear from Pogona vitticeps
showing neoplastic leukocytes characterized by pleomorphic nuclear shape, moderate numbers of variably
sized, well-delimited, clear cytoplasmic vacuoles, and
euchromatic chromatin patterns without distinct nucleolar rings.
Figure 2. Bone marrow aspirate from Pogona vitticeps showing a vast majority of leukocytic precursors
consisting of neoplastic cells with identical morphology to those found in peripheral blood supports a
diagnosis of monocytic leukemia.
monocytes/ll, 63 3 103 heterophils/ll, and 48.3 3
103 lymphocytes/ll. The concurrent presence of
heterophilia and lymphocytosis was interpreted as
paraneoplastic inflammation. Plasma chemistry
showed resolution of previously noted hyperglycemia. A bone marrow aspirate was taken from
the right femur using sterile technique and a 25g
5/8-inch needle. Cytologic evaluation of the
marrow confirmed a leukemia with a vast majority
of leukocytic precursors consisting of neoplastic
cells with identical morphology to those found in
peripheral blood; additionally myeloid (heterophilic) and lymphoid hyperplasia were present
(Fig. 2).
Chemotherapy with cytosine arabinoside (Cytosar; Pharmacia and Upjohn Ltd., Peapack, New
Jersey 07977, USA) was initiated at a dose of 100
mg/m2. The enclosure was kept at a temperature
range of 90 to 1008F during the treatment period
to encourage higher metabolic rates during drug
administration. Normosol R was used to dilute
the stock solution of 12.5 mg/ml Cytosar to a 0.78
mg/ml solution which was administered i.v. at a
rate of 0.3 ml/hr for 48 hr. A total dose of 11.2 mg
was to be administered over a 48-hr period.
Respiratory rate and activity level were observed
every 3 hr during the treatment phase and
remained stable until the dragon became acutely
unresponsive at approximately 44 hr into treatment. Resuscitation attempts were initially successful; however, less than 1 hr later the patient
died.
Necropsy was performed the day following
death and showed significant infiltration of can-
cerous cells in the heart, skeletal muscle, gastrointestinal tract, liver, kidney, lung, and cloacal
tissue. Grossly, multiple thrombi were noted in
the liver and lungs along with petechiation of the
intestines, suggestive of disseminated intravascular coagulation. The cancerous cells were round
cells with moderate amounts of cytoplasm and
indistinct cell borders. The nuclei were round to
oval with finely stippled chromatin and occasional
prominent nucleoli. There was marked anisocytosis and anisokaryosis, but mitosis was noted in
less than one per five high-power fields. In the
tissue, the neoplasm was infiltrative and nonencapsulated with pronounced perivascular cuffing.
Immunohistochemistry for CD3 cell markers was
performed and was negative in the neoplastic cell
population.
Several slides were submitted to a second
pathology service for a second opinion given the
difficulty of interpreting cell lineage in reptiles,
particularly when the cells are atypical in appearance as were the neoplastic cells. The second
interpretation was similar to the original, describing the cells as round to ovoid with hyperchromatic nuclei, central nucleoli, and occasional
mitoses; however, the cell line was interpreted as
lymphoid, most likely a B-cell tumor based on
plasmacytoid cell morphology. Renal nephrolithiasis with secondary ductular rupture and associated coelomitis also were reported.
Neoplasia is becoming more frequently diagnosed and characterized in reptiles. This may be a
result of longevity in captivity;13 however, many of
the lizards in which neoplastic processes are seen
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324
JOURNAL OF ZOO AND WILDLIFE MEDICINE
are middle aged.4 Types C and A retroviruses have
been identified in several patients that have died
from lymphoid neoplasms.19 Sarcomas and lymphomas are the most frequent tumors recognized
in reptiles.4,25 Lymphoblastic leukemias are less
common and may be seen with or without
lymphoma recognized on histopathology.4,13
These patients typically present with systemic
signs, oral pathology, or occasionally, multiple
subcutaneous masses.1,5,11 Myeloid leukemias are
rare in humans and small animals and generally
have a poor prognosis.3,12 They have been identified in only a few reptile species, including an
Aruba Island rattlesnake (Crotalus unicolor), a
carpet python (Morelia spilota),5 a Mobile terrapin
(Pseudemys elegans),3 and an Honduran milk snake
(Lampropeltis triangulum hondurensis).7 Treatment
was not attempted in any of these cases. Acute
monocytic leukemia has been diagnosed in one
bearded dragon, but treatment was not attempted.15
As neoplasias only relatively recently have
been recognized as important pathologic processes in reptiles, therapy is still in the experimental
stages. A king cobra (Ophiophagus hannah) with
lymphoma was treated with L-asparagine aminohydrolase, vincristine, and prednisolone initially,
then with prednisolone and chlorambucil. The
snake was found dead 15 mo after presentation.
Cytosine arabinoside has been used to treat
lymphoma in a rhinoceros viper (Bitis nasicomis)
at a dose of 30 mg/kg s.c. q 24 hr for 48 hr.9 The
snake died 24 hr after the first treatment. Severe
tubular necrosis was considered the cause of
death and was suggested to be a result of cytosine
arabinoside; however, the animal had received
gentamicin, which also is known to cause multifocal tubular necrosis.9,10 Cytosar also was used in
combination therapy with good results in a
diamondback terrapin (Malaclemys terrapin) suffering from lymphoblastic leukemia.14 The animal
was treated with prednisone, cytosine arabinoside, and chlorambucil. At 24 days posttreatment, the white blood cell count had improved
and the patient’s activity level had increased to
preillness levels. However, the patient died 46
days after beginning treatment.14
An aggressive chemotherapeutic regimen was
used, in this case, because of the advanced clinical
state of the patient and poor prognosis. Furthermore, i.v. administration mimicked the most
appropriate method of administration in mammalian species and provided immediate and
accurate chemotherapeutic dosing. The coccygeal
vein was selected for ease of maintenance and
decreased risk of bending or obstruction of the
catheter. Despite the relatively high dose and i.v.
administration of cytosine arabinoside, no evidence of renal failure or other organ failure
related to administration of the drug was noted
on histopathologic evaluation. In the case of
suspected cytosine arabinoside toxicity in a
rhinoceros viper, toxic effects were seen within
24 hr.9 Patients in earlier stages of disease may
benefit from treatment with cytosine arabinoside.
It is possible that the adverse effects of cytosine
arabinoside were not identified in this case due to
acute toxicity or changes secondary to neoplasia
and coelomitis.
This case illustrates the difficulty of determining cell lineage in reptiles, particularly antemortem. Identification of T lymphocytes through
CD3 markers typically is accurate in reptilian
species; however, B-cell markers, including
CD79a, are not as reliable.15 Therefore, much of
the interpretation relies on cellular characteristics, which may be modified in neoplastic processes. Given this dilemma, determining the most
appropriate treatment may be difficult. Prednisone therapy is widely used and accepted for
patients with lymphoid leukemia and lymphoma,
but was not used in this case because typically it is
not as effective for myeloid leukemias.2 Cytosine
arabinoside was chosen because it is the most
frequently used treatment for mammals with
chronic monocytic leukemia.2 The dose administered, 100 mg/m2, was extrapolated from recommendations for mammalian patients as no basis
exists for chemotherapeutic dosing in reptilian
species.6,10 Because mammalian metabolic rates
are higher than those of reptilian species, the
temperature gradient in the enclosure was kept
high to help maintain a high metabolic rate in this
patient. Electron microscopy and further immunochemical and cyto-histochemical staining were
not pursued in this case, but may have helped
elucidate the origin of the neoplastic cells in this
bearded dragon.
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Received for publication 3 September 2010
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