Full text of DOI:10.1111/j.1751-0813.2001.tb10923.x

Clinical
Therapy for Australian cats with
lymphosarcoma
Australian
VETERINARY
JOURNAL
a
ab
a
c
b
R MALIK , LJ GABOR , SF FOSTER , BE McCORKELL and PJ CANFIELD
Faculty of Veterinary Science, The University of Sydney, New South Wales, 2006
C L I N I C A L S E C T I O N
EDITOR
Objective
To determine the response of Australian cats with lymphosarcoma to
MAUREEN REVINGTON
chemotherapy and/or surgery in relation to patient and tumour characteristics,
haematological and serum biochemical values and retroviral status.
ADVISORY COMMITTEE
ANAESTHESIA
PETER GRAY
Design
Prospective study of 61 client-owned cats with naturally-occurring
lymphosarcoma subjected to multi-agent chemotherapy and/or surgery.
AQUATIC ANIMAL MEDICINE AND HEALTH
BRADLEY CHADWICK
Procedure An accepted chemotherapy protocol utilising l-asparaginase,
AVIAN MEDICINE AND SURGERY
vincristine, cyclophosphamide, doxorubicin, methotrexate and prednisolone was
modified and used to treat 60 cats with lymphosarcoma. Clinical findings were
recorded before and during therapy. As far as practical, cases were followed to death,
euthanasia or apparent cure. Owner satisfaction with the results of chemotherapy
was determined using a questionnaire sent after the completion of chemotherapy.
SHANE RAIDAL
CLINICAL PATHOLOGY/BIOCHEMISTRY
MARY McCONNELL
CRITICAL CARE/EMERGENCY MEDICINE
ALICIA FAGGELLA
EPIDEMIOLOGY
CHRIS BALDOCK
Results
One cat, with lymphosarcoma limited to a single mandibular lymph node,
EQUINE MEDICINE AND SURGERY
was treated using surgery alone and was cured. The other 60 cats were treated using
multi-agent chemotherapy, although seven cats with localised intestinal, ocular and
subcutaneous lesions had these lesions partially (2 intestinal lesions) or completely (2
eyes, 2 intestinal lesions and a cluster of regional lymph nodes) resected prior to
starting chemotherapy. The median survival time for these 60 cats was 116 days. Of
the 60 cats, 48 rapidly went into complete remission following the administration of l-
asparaginase, vincristine and prednisolone (complete remission rate 80%) and these
cats had a median survival of 187 days.
KATE STEEL
LABORATORY ANIMAL MEDICINE/HEALTH
DAVID PASS
OPHTHALMOLOGY
ZIGRIDA CHESTER
PRODUCTION ANIMAL MEDICINE
HELEN CHAPMAN
SMALL ANIMAL MEDICINE
PETER IRWIN
SURGERY
RICK READ
Three cats were censored from further analysis as their long-term survival data
were uninterpretable because they died of causes unrelated to lymphosarcoma or
were prematurely lost to follow-up. Twenty cats were classed as ‘long-term survivors’
based on survival time in excess of one year and at least 14 were ‘cured’ based on
the absence of physical evidence of lymphosarcoma 2-years after initiating treatment.
In other words, of the 48 cats that reached complete remission, in excess of 29%
were ‘cured’.
WILDLIFE AND EXOTIC ANIMAL
MEDICINE/SURGERY
RALPH SWAN
EDITORIAL ASSISTANT AND
DESKTOP PUBLISHING
ANNA GALLO
Despite detailed analysis, few meaningful prognostic indicators based on patient or
tumour characteristics were identified, although long-term survivors were more likely
to be less than 4-years (P= 0.04) and to have tumours of the T-cell phenotype (P=
0.06). Excluding the one FeLV ELISA-positive cat with mediastinal LSA, 7 of 9 cats
less than 4 years-of-age were long-term survivors (median survival time >1271 days).
There was a strong association between achieving complete remission and long-term
survival (P = 0.003).
On the basis of 27 replies to a questionnaire, owners were generally very satisfied
with the response to chemotherapy, irrespective of the survival time of the individual
patient. Eighty five percent of owners expressed complete satisfaction with their
decision to pursue chemotherapy and 70% believed their cat’s health status improved
during the first 2-weeks of treatment. Importantly, 78% of owners considered that
chemotherapy required a very substantial time commitment on their part.
CONTRIBUTIONS INVITED
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invited to contribute clinical articles to the
Australian Veterinary Journal. We will
consider material in a variety of formats,
including clinically orientated reviews,
reports of case series, individual case
studies, diagnostic exercises, and letters
containing
comments
or
queries.
Practitioners are also invited to contribute
to the case notes feature, where accepted
articles are not peer reviewed but are
edited for publication. Contributors should
consult instructions to authors and recent
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Send all contributions to:
Conclusions It was possible to cure approximately one quarter of cats with
lymphosarcoma using sequential multi-agent chemotherapy and/or surgery. FeLV-
negative cats younger than 4 years (typically with mediastinal lymphosarcoma) had a
particularly favourable prognosis. The decision to embark on chemotherapy should
be based on the results of induction chemotherapy with l-asparaginase, vincristine
and prednisolone, as the response to this was a good predictor of long-term survival.
Cats surviving the first 16 weeks of chemotherapy generally enjoyed robust
remissions (in excess of 1 year) or were cured of their malignancy.
Editor, AVJ Clinical Section
Aust Vet J 2001;79:808-817
Key words: Lymphosarcoma, malignant lymphoma, cat, feline leukaemia virus, feline immunodeficiency
virus, chemotherapy, doxorubicin, l-asparaginase.
AVA House, 272 Brunswick Road,
Brunswick, Vic. 3056,
Phone: (03) 9387 2982
Fax: (03) 9388 0112
a
Email: desktop@ava.com.au
Department of Veterinary Clinical Sciences
b
Veterinary Anatomy and Pathology
c
Department of Primary Industries, Water and Environment
808
Aust Vet J Vol 79, No 12, December 2001

Clinical
his is the final paper in a series that has examined a large
cohort of cats with naturally-occurring LSA from the
Sydney region. Cats were recruited into the study to
are progressing in canine LSA28 and similar data are emerging
for cats also. To date, the most useful prognostic indicators in
cats are FeLV status, the anatomical distribution of lesions and
the initial response to chemotherapy.11,12,15-25 Attempts to relate
prognosis to surface antigens and proliferation indices have not
been fruitful.23,25 The literature suggests that cats with LSA
treated using chemotherapy have shorter median remissions,
fewer side effects and a higher proportion of patients that are
eventually cured compared to dogs with LSA. There seems to be
a consensus that protocols containing doxorubicin result in
longer remissions and survival times,21-24 although this agent
alone is less effective in inducing remission in cats compared
with vincristine (with or without l-asparaginase).13 Best results
to date have been obtained using multi-agent protocols similar
to those introduced by Matus and McEwen and their colleagues
from the Donaldson-Atwood Cancer Clinic, AMC (New York
city) and the University of Wisconsin.24,29
In the present study, the outcomes for a cohort of 60
Australian cats with LSA treated with the same multi-agent
chemotherapy protocol were determined in an attempt to
identify patient and tumour factors associated with a favourable
long-term prognosis. The results of chemotherapy, measured
quantitatively in terms of survival statistics, and qualitatively in
terms of a questionnaire distributed to owners subsequent to
completion of the chemotherapy protocol, are reported. The
questionnaire also covered a variety of issues concerning the
process of referral and owner expectations relevant to
veterinarians about to embark on this course of therapy.
T
encompass the range of presentations of LSA encountered
commonly by veterinary practitioners. The first three papers
defined patient and tumour characteristics and
clinicopathological derangements that occurred in cats with LSA
and provided information on the spectrum of disease conditions
that develop with this malignancy.1-3 The subsequent two papers
examined the potential contribution of FeLV and FIV infection
to the development of LSA.4,5
The prime motivation for embarking on this study was to
attempt to correlate signalment, tumour characteristics,
laboratory findings and the retroviral status of cats with the
response to a single treatment regimen, in order to predict those
cats in eastern Australia most likely to benefit substantially from
chemotherapy. This aim was relevant to mainstream small
animal practice, as LSA is probably the most common tumour
of cats.6-8 It was considered that the information generated by
this project would be especially useful to Australian practitioners
because the gene pool in our cat population9 and the particularly
high prevalence of FIV in relation to FeLV10 would make
extrapolation from overseas data unreliable. The relative ease of
administration of chemotherapy drugs and the limited side-
effects typically experienced by feline patients at dosages
commonly used11,12 make chemotherapy a good alternative to
euthanasia or palliative dosing with prednisolone. Indeed,
treatment of cats with LSA is considerably less expensive than
treating dogs with LSA (especially large canine patients), as
cytotoxic drugs are used in much smaller quantities. The recent
decrease in the cost of doxorubicin13 has further improved the
affordability of multi-drug protocols incorporating this agent,
while the availability of sevoflurane anaesthesia14 to restrain
temporarily cats during IV chemotherapy makes the mechanics
of performing the procedure simpler, easier and quicker than in
the past. Finally, recent detailed reports of survival times for
North American cats treated with chemotherapy protocols are
promising in terms of remission times, quality of life and the
possibility of cure in a select proportion of cases.11,12,14-25
Materials and methods
Case selection/Diagnosis/Investigation
In the present study, 60 of 118 cats diagnosed with LSA
received treatment with curative intent using a single multi-
agent chemotherapy regimen. A further cat with LSA restricted
to a single lymph node was treated by simple surgical excision
alone. The chemotherapy regimen was based on an AMC
protocol,29 except that the order and route of some treatments
were altered to make the course of therapy more convenient to
owners. Also, increased doses of vincristine, l-asparaginase and
doxorubicin were utilised once cats were in remission in an
attempt to increase the proportion of cats that would be cured
or be maintained in robust clinical remission. In seven cases,
resectable lesions (typically involving the gut, eye or
subcutaneous tissue) were excised prior to starting drug therapy.
The 62 cases of feline LSA that form the basis of this study
have already been described in detail with respect to a number
of characteristics.1-5 These features were also considered in the
analysis of this study. In summary, veterinarians in Sydney and
its environs were provided with free diagnostic laboratory
services for suspected cases of feline LSA. In those cases where
the diagnosis was confirmed, subsidised treatment was offered.
Cats were recruited into the study over an 18 month period
from September 1995 to February 1997 and followed until
November 2000 in order to assess the response to therapy in
terms of disease free interval, long-term survival and incidence
of unforseen sequellae. The consent of owners for inclusion in
this trial was obtained in all cases.
In human patients with lymphoma, histological classification,
clinical staging and presence or absence of secondary clinical
signs are well correlated with response to specified chemo-
therapy protocols.26,27 Attempts to identify similar correlations
AMC
DSH
ELISA
FeLV
FIV
HIV
IBD
IM
IP
Animal Medical Centre
Domestic short haired cat
Enzyme-linked immunosorbent assay(s)
Feline leukaemia virus
Feline immunodeficiency virus
Human immunodeficiency virus
Inflammatory bowel disease
Intramuscularly
Intraperitoneally
Intravenously
Lost to follow-up
Lymphosarcoma(s)
IV
LTFU
LSA
PO
Orally
Patient characteristics and physical findings were recorded.
LSA was diagnosed on the basis of physical findings, radio-
graphic and/or sonographic images and results of needle-
aspirate cytology and/or histology. In all patients that went on
to receive treatment, enough tissue was obtained, using either
PCR
PCV
RBC
SC
Polymerase chain reaction
Packed cell volume
Red blood cell
Subcutaneously
University Veterinary Centre, Sydney
UCVS
Aust Vet J Vol 79, No 12, December 2001
809

Clinical
surgery or a core biopsy device, to make a histological diagnosis
of LSA and to determine the histological grade and
immunophenotype of the tumour. A modified scheme for
anatomical classification of LSA was devised, including a ‘mixed’
category for cases that involved two or more anatomical forms.1
Histological classification of neoplasms followed the Working
Formulation Classification System.2,30 Four multispecies cross-
reactive antibodies were used to classify tumours as having a B-
or T-cell phenotype.2 Haematological analysis usually included
determination of PCV, haemoglobin concentration, RBC and
leukocyte counts, differential leukocyte count, reticulocyte
count and examination of buffy-coat smears for neoplastic cells.3
Serum biochemical analysis was primarily done with a Cobas
Mira wet chemistry analyser and included a panel of commonly
used analytes. An ELISA was used to detect FeLV p27 antigen in
serum and a PCR was used to detect FeLV DNA in formalin-
fixed, paraffin-embedded tissue sections containing neoplastic
lymphoid cells. The PCR was designed to amplify a highly
conserved region of the untranslated long terminal repeat of
FeLV provirus.4 When only core biopsy specimens had been
obtained, there was insufficient tissue for FeLV PCR studies.
Western blot analysis was used to determine the presence of FIV
antibodies in serum.5
which the agents were administered was altered such that
treatments requiring a visit to the clinic were given once a
fortnight (rather than weekly) during the 15 week induction
stage. The initial dose of prednisolone administered (4 mg/kg
PO once daily) was higher than has been used previously for
feline LSA. l-asparaginase was administered twice rather than
once and given SC or IM, rather than IP. Finally, after week 1,
the administered doses of vincristine, and in some cases
doxorubicin, were slightly higher than currently recommended
for cats. Specific details of the protocol are given in Table 1.
Generally, IV chemotherapy was given via the external jugular
vein of cats restrained using light anaesthesia. Cats were not
premedicated with antihistamines but sedated with
a
combination of ketamine (3-6 mg/kg) and either midazolam
(0.3 mg/kg) or acepromazine (0.05 mg/kg), mixed together in
the same syringe and given SC or IM. About 5 minutes after the
injection of the sedative combination, a light plane of gaseous
anaesthesia was induced and maintained by inhalation of
halothane or isoflurane in a 2:1 mixture of nitrous oxide and
oxygen using a tight-fitting face-mask attached to a non-
rebreathing system. The fur over the external jugular vein was
clipped, the area prepared with 70% ethanol, the vein raised,
and venipuncture was performed using a 23 gauge butterfly
Almost all cats were encouraged to enrol in the trial, even
those with advanced or severe disease, anaemia or
substantial loss of body mass. Thus many cats with
advanced or disseminated disease and/or loss of body
condition were entered into the trial in spite of a likely
poor prognosis. In discussing potential therapy with
clients, the only recruiting bias was the strong
encouragement to owners of young cats with mediastinal
LSA to undergo therapy, as our experience, that of others
(V Menrath, personal communication) and anecdotal
reports in the literature31 indicated that these cats often
did very well.
Table 1. Sequential multi-agent chemotherapy protocol used to treats cats with LSA
Induction phase Drugs and route of administration
Place of administration
Week 1
Vincristine 0.025 mg/kg IV;
l-asparaginase 450 IU/kg SC;
prednisolone 4 mg/kg PO daily
Hospital
Week 2
Week 3
Cyclophosphamide 10 mg/kg PO
Home
Doxorubicin 20 mg/m2 or 1 mg/kg IV;
prednisolone 3 mg/kg PO daily
Hospital
Week 4
Week 5
Week 6
Week 7
Week 8
Week 9
No IV or PO cytotoxic therapy;
prednisolone 2 mg/kg daily
Home
Treatment
Vincristine 0.03 mg/kg IV;
Prednisolone 2 mg/kg daily
Hospital
Home
Of 118 cats in which LSA was diagnosed, 62 cases were
treated. One cat, with involvement of a solitary peripheral
lymph node, was treated by excision of the affected node;
the owners of this cat declined the adjuvant chemotherapy
that was recommended. One cat was treated, but incorrect
doses of chemotherapy agents were administered, so data
from this patient were excluded. The remaining 60 cats all
received essentially the same multi-agent chemotherapy
protocol. Early in the trial, in the light of evolving
experience and new information in the literature, the total
duration of chemotherapy was reduced from 2 years to 18
Cyclophosphamide 10 mg/kg PO;
prednisolone 1 mg/kg daily
Doxorubicin 25 mg/m2 or 1.1 mg/kg IV;
prednisolone 1 mg/kg daily
Hospital
Home
No IV or PO cytotoxic therapy;
stop prednisolone
Vincristine 0.03 mg/kg IV;
Hospital
l--asparaginase 450 IU/kg SC
Week 10
Week 11
Week 12
Week 13
Week 14
Week 15
Cyclophosphamide 10 mg/kg PO
Vincristine 0.03 mg/kg IV
Home
Hospital
Home
months and the dose of doxo-rubicin that was initially
Methotrexate 0.8 mg/kg PO
Vincristine 0.03 mg/kg IV
based on surface area was subsequently based on body
weight.32 Likewise, l-asparaginase was initially administered
SC, but the route of administration was changed later to
IM.33 Owners were encouraged to bring their cats to the
UCVS for treatment, but where this was not possible,
drugs were delivered to the referring veterinarians who
then administered the agents according to our protocol. In
some cases, local veterinarians administered vincristine,
while doxorubicin and l-asparaginase were administered at
UCVS.
Hospital
Home
Cyclophosphamide 10 mg/kg PO
Doxorubicin 25 mg/m2 or 1.1 mg/kg IV
Hospital
Maintenance phase
Week 17
Week 19
Week 21
Week 23
Vincristine 0.03 mg/kg IV
Hospital
Home
Cyclophosphamide 10 mg/kg PO
Vincristine 0.03 mg/kg IV
Hospital
Home
Methotrexate 0.8 mg/kg PO
The AMC chemotherapy protocol29 was modified in a
number of ways. Cyclophosphamide and methotrexate
were administered PO rather than IV. The order in
The maintenance cycle was repeated, with biweekly treatments, that is, hospital
visits every month. After year, the maintenance cycle was continued, except
1
treatments were given every 4 weeks rather than every 2 weeks. After 18 months, a final
treatment of doxorubicin was administered before treatment was discontinued.
810
Aust Vet J Vol 79, No 12, December 2001

Clinical
Study limitations, definition of short-term and long-term survival
and clinical cure
needle, which was subsequently threaded all the way to its hub.
The integrity of the vein was checked by aspiration of blood
and test injection of 3 to 4 mL of sterile saline, prior to
administration of the cytotoxic agent. The calculated dose of
vincristine (0.1 mg/mL solution) was given undiluted over 5 to
10 seconds. The calculated dose of doxorubicin was diluted to a
total volume of 5 to 6 mL with sterile saline, and administered
slowly IV over 1 to 2 minutes. Following administration of
these agents, the butterfly needle was flushed using a further 5
to 10 mL of sterile saline to ensure that, if extravasation
occurred, irritant drugs would not reach the subcutaneous
tissues. In some critical cases, typically cats with dyspnoea due
to mediastinal masses, vincristine was administered via the
cephalic vein under sedation (rather than using gaseous
anaesthesia) and prednisolone was initially administered IV or
SC (rather than PO). l-asparaginase was administered SC or IM
using a 2000 U/mL solution. All other drugs were administered
PO. Cats were treated on an outpatient basis, except in cases
with renal LSA, where patients were initially diuresed using IV
fluids until kidneys had returned to normal size and function, as
assessed by resolving azotaemia and return of appetite. The
majority of cats were given doxycycline (5 mg/kg PO twice
daily) or enrofloxacin (5 mg/kg PO daily) for antimicrobial
prophylaxis during the induction phase of chemotherapy.
There were a number of difficulties in determining the
response to multi-agent chemotherapy for this cohort of LSA
cats. Firstly, it was difficult to ensure good follow-up of all cases,
especially when cats did not do well and owners were
unprepared to permit additional investigations or necropsy. This
meant that it was sometimes impossible to determine whether a
cat’s demise was attributable to recurrent LSA, side-effects of the
chemotherapy protocol (drug toxicity, pancreatitis), secondary
infections (eg bacterial sepsis, toxoplasmosis) or concurrent
disease (eg nephritis). Secondly, it was very difficult to determine
whether a patient had been cured (defined as complete remission
for 2-years after starting chemotherapy), especially in older cats
that remained in remission but succumbed to other disease
processes, for example renal failure. Although necropsy
examination and appropriate histology would have resolved this
issue, this was not always possible. Thirdly, many cats died
during the course of chemotherapy for completely unrelated
reasons, such as motor vehicle trauma, which made
interpretation of their survival time problematic. Finally, it was
impossible to determine with accuracy whether disease processes
(eg myocardial failure, renal failure) which resulted in a given
cat’s demise were attributable to age per se as opposed to a side
effect of the chemotherapy protocol (for example doxorubicin-
induced nephrotoxicity).
Follow-up
As a result of these difficulties we adopted a different approach
to the presentation and analysis of the survival data for LSA cats
treated using chemotherapy, by dividing patients into ‘long-term
survivors’ (alive in excess of 12-months following initiation of
chemotherapy) and ‘short-term survivors’ (death or euthanasia
occurring during the first year of chemotherapy). Also, we
deliberately delayed analysis of the data until at least two years
after completion of chemotherapy regimens in all cats in an
attempt to determine whether long-term survivors were indeed
‘cured’ and to ascertain the longevity of treated cats.
Clinical remission was assessed by physical examination and
sometimes radiography or ultrasonography depending on the
site and extent of the tumour. Complete remission was defined
as disappearance of all palpable tumour and associated clinical
signs. For cats without palpable abnormalities, responses were
gauged on the basis of physical findings and clinical signs, for
example, maintenance of body mass or weight gain, resolution
of vomiting, diarrhoea, nasal discharge (as appropriate) and
improved appetite. In cats with mediastinal involvement,
remission was determined using follow-up radiography. A
partial response was defined as > 50% decrease in the size of
tumour(s). Duration of first remission was defined as time from
administration of the first chemotherapy to relapse of clinical
disease. Survival time was the time from onset of treatment
until death, euthanasia or last contact with the owners (when
the case was lost to follow-up). These times were calculated
electronically using a 360 day calendar year. At the time of first
relapse, owners were given the option of stopping all treatment
or continuing some portion of the protocol, as specific rescue
protocols were not utilised. Cats were considered cured if they
were alive 2-years after starting chemotherapy. Unfortunately,
many cats died of reasons other than LSA or were lost to follow-
up 1 to 2 years after starting chemotherapy; these cases were
considered as ‘probably cured’.
Statistical analysis
Cases were analysed statistically for response (complete
remission, partial remission or no remission), duration of first
remission and survival time. Factors examined included patient
characteristics (age, breed, sex, FIV and FeLV status) and
tumour characteristics (anatomical classification, tissue
involvement, immunophenotype, histological grade, FeLV
status) and clinicopathological values. To simplify the statistical
analysis, the histological subtypes were reduced from six2 to
three categories: low grade (type A, B and C), medium grade
(type G and F) and high grade (type H and I). For categorical
data, a combination of likelihood χ2 and log-linear regression
was used. All conceivable 2-factor models were used to test for
potential associations. When the expected frequencies were less
than five, Fischer’s exact tests were used. The ages of long-term
and short-term survivors were compared using the Mann
Whitney U test. The outcomes for cats less than 4-years and cats
older than 4-years were compared using Fisher’s Exact test. The
statistical analysis was performed using Genstat and Instat
statistical software programmes. P values less than 0.05 were
Adverse side effects were assessed by evaluating owners’
reports and by physical examination. When adverse side effects
were encountered, the doses of agents given subsequently were
usually reduced empirically and/or the agents were given at
longer intervals than normal. Episodes of presumed sepsis were
treated using alternative antibiotics, typically amoxicillin
clavulanate or enrofloxacin.
considered significant
.
Survey of owner satisfaction with therapy
Results
On 15th January 1999 all owners of treated cats were sent a
questionnaire (Table 5) and a stamped self-addressed envelope.
Of the 61 letters sent, 27 replies were received.
Sixty cats received chemotherapy using the protocol described
in Table 1, while one additional cat, which is considered
Aust Vet J Vol 79, No 12, December 2001
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Clinical
Long-term survivors
separately, was treated using surgery alone. Of the 60 cats
treated using chemotherapy, 48 went into complete remission
following administration of l-asparaginase, vincristine and
prednisolone (Table 1, week 1; complete remission rate 80%),
two were considered to be in partial remission, while the
remaining 10 cases showed little or no response. The response
to chemotherapy was typically rapid, with most cats achieving
remission within 5 to 7 days of starting therapy. The overall
median survival period for all 60 cats was 116 days, with a range
of 7 to >1491 days. The corresponding median duration of
complete remission was 112 days (range 0 to >1491 days).
Considering only the 48 cats that had a complete remission, the
median survival was 187 days (range 9 to >1491days). It should
be borne in mind that the stated survival times are
underestimates, as several cats died of causes unrelated to LSA
(for example vehicular trauma) or were LTFU; for the purpose
of our analysis, survival times in these cats were recorded as
either the time of death or greater than the last time of contact
with the patient, respectively.
Of the 57 cats treated using chemotherapy and for which
long-term survival data could be interpreted, 20 (35%) were
considered ‘long-term survivors’, while 37 (65%) cats were
considered ‘short-term survivors’. Three cats could not be
categorised as being short as opposed to long-term LSA
survivors and were therefore censored from the statistical
analysis; one of these cats was killed by vehicular trauma (while
in remission) 88 days after starting chemotherapy, one cat was
LTFU (while in remission) after 85 days because of the marital
breakdown of its owners, while the remaining cat with nodal
LSA developed renal failure while in complete remission and
died 200 days after starting chemotherapy.
The 20 cats in this category had a median age of 90 months
(range 9 to 192 months) at diagnosis and 14 (70%) were male.
These 20 cats had a median survival time of >835 days (range
>365 to >1491 days). Long-term survivors were significantly
younger than short-term survivors (median age 90 months
versus 120 months; P = 0.02). Eight were either alive (5 cats;
survival times greater than 1168, 1169, 1271, 1327 and 1405
days ) or thought to be alive (3 cats; LTFU at 365, 538 and 669
days ) at the time of writing. Two other long- term survivors
probably developed recurrent LSA (19 and 27 months after
starting chemotherapy) and were euthanased. A further 10 cats
experienced a number of variably characterised disease
conditions (8 cats) or accidents (2 cats) that resulted in death 17
to 43 months after starting chemotherapy (Table 2). It is
conceivable that at least some of the disease conditions that
resulted in the demise of this subgroup were referable to
undiagnosed recurrent LSA or long-term sequellae of
chemotherapy drugs (for example doxorubicin induced
myocardial damage or nephrotoxicity); it is also possible that
these disease conditions were related merely to the age of the cats
or pre-existing chronic conditions such as FIV infection,
pancreatitis, interstitial nephritis etc.
It is very difficult to determine with certainty whether a cat
with LSA had been cured, as evidenced by two cats in the
present series which probably developed recurrent LSA, 19 and
27 months after starting treatment. However, survival beyond 2-
years is likely to represent a cure in most instances, and 17 of the
20 long-term survivors either lived longer than 2-years, were
shown not to have LSA at necropsy or died of motor vehicle
trauma while in long-standing clinical remission.
One cat with LSA restricted to a single lymph node was
treated using simple surgical excision of the affected node,
without follow-up chemotherapy. This cat remained well 4-years
following surgery, with no evidence of recurrent LSA.
Another way of presenting the same information was to
consider the long-term survival of cats alive at the end of the 15
week induction phase of chemotherapy. The 29 cats surviving
this phase of chemotherapy comprised nearly half of the cats
subjected to chemotherapy and had a median survival time of
>728 days (range 120 to >1491 days).
Factors affecting long-term survival
Despite rigorous analysis of the data (Table 3), very few
associations between patient and tumour characteristics and
long-term survival were detected. Cats achieving a complete
remission were more likely to be long-term survivors (P =
0.003). Tumour immunophenotype had a significant effect on
survival (P = 0.03): cats with T-cell tumours were more likely to
be long-term survivors (P = 0.06), whereas cats with B-cell
tumours were more likely to be short-term survivors (P = 0.05).
Age was also a factor affecting survival, as long-term survivors
were significantly younger than short term survivors (see earlier).
Stated another way, 7 of 10 (70%) cats less than 4 years-of-age
were long-term survivors, compared with 13 of 47 (28%) cats
older than 4 years (P= 0.02; Fisher’s Exact test). The likelihood
of long-term survival in young cats would have been even higher
(7 of 9 cats; P = 0.007) had the 2-year-old cat with FeLV
antigenaemia and mediastinal LSA been excluded from the
analysis, as this patient survived only 26 days. This case was
atypical because FeLV infection is rare in eastern Australia,10
with only 2 of 118 LSA cats in the present cohort having FeLV
antigenaemia.4 It is impossible to determine with certainty
whether the excellent prognosis for the 7 FeLV antigen-negative
cats less than 4-years was related to age per se,
immunophenotype or anatomical form (mediastinal: 4 T-cell, 2
non B-/non T-cell; abdominal: 1 B-cell). The influence of age on
outcome in cats with mediastinal LSA is shown in Table 4.
Short-term survivors
The 37 cats in this category had a median age of 120 months
(range 12 to 180 months) at diagnosis and 24 (65%) were male.
These 37 cats had a median duration of first remission of 56
days (range 0 to 253 days) and a median survival time of 69
days (range 7 to 288 days). Ten cats did not go into remission
and either died or were euthanased as a result of their LSA, with
survival times of 7, 19, 21, 23, 24, 26, 28, 37, 69 and 107 days.
Two cats went into partial remission and survived 65 and 165
days. The remaining 25 cats went into complete remission, but
subsequently came out of remission and died or were
euthanased (20 cats) or died of other causes (wasting syndrome
- 2 cats; renal failure - 1 cat; toxoplasmosis - 2 cats). The two
patients that succumbed to a ‘wasting syndrome’ were
apparently in remission but died 81 and 171 days after starting
chemotherapy. One cat with renal LSA went into remission but
remained azotaemic, probably as a result of pre-existing chronic
interstitial nephritis, and was euthanased 9 days after starting
treatment. Two cats died of acute toxoplasmosis: one cat (FIV-
positive) with mediastinal LSA went into remission following
induction therapy but died of mediastinal toxoplasmosis 13
days later, while another cat (FIV-negative) died of recurrent
LSA and concurrent toxoplasmosis 28 days after starting
therapy.
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Aust Vet J Vol 79, No 12, December 2001

Clinical
Table 2. Data concerning 12 LSA cats that were ‘long-term’ survivors (alive in excess of 12 months following
initiation of chemotherapy) but died; an additional 3 long-term survivors were lost to follow up, while 5 more
were known to be alive at the time of writing.
of chemotherapy being spread
over
a 6-month period as
opposed to an up-front fee.
Case No.
Comment
Survival period
(days)
FIV status
(Western blot)
Discussion
1
2
3
4
Run-over by a truck; in remission
512
517
728
753
Negative
Negative
Positive
Positive
The results of multi-agent
chemotherapy for our cohort of
cats with LSA (complete
remission rate 80%; median
survival time 116 days) are
broadly similar to those reported
for similar protocols used in
Died acutely at home; cause not determined; no necropsy
Died of chronic renal failure; no evidence of LSA at necropsy
Initially had intestinal LSA; developed LSA of larynx 195 days after
finishing 18 months of chemotherapy; given further chemotherapy,
but died of undetermined disease while in remission; no evidence of
LSA at necropsy
North
Specific comparison
individual North American
series is problematic, as different
referral centres have differing
American
studies.
with
5
6
Euthanased because of ‘arthritis’ while still in remission; no necropsy
781
820
Negative
Negative
Ocular LSA; developed likely recurrent LSA in contralateral eye
resulting in euthanasia; no necropsy
7
8
9
Died quietly at home; cause of death not determined
Run-over by the owners car while in remission
824
845
912
Positive
Negative
Positive
proportions
of
various
anatomical forms (sometimes
correlated with different survival
statistics), different percentages
of FeLV/FIV positivity and cats
Initially had solitary nodal LSA. Developed IBD 11 months into the
chemotherapy protocol; treated with prednisolone, metronidazole
and chlorambucil; eventually euthanased because of refractory IBD;
necropsy not permitted
of
a
differing
genetic
Furthermore,
chemotherapy
10
11
12
Initially had nasal LSA. Later developed a prednisolone-responsive
laryngeal condition. Eventually was euthanased because of a solitary
lung mass and renal failure.
753
Positive
Positive
Negative
constitution.
different
protocols were often adopted,
even within the same study
cohort. Reported complete
remission rates vary between 50
and 87%, while median survival
times range from 50 to 281
days.11,12,15-25
Initially had mediastinal LSA. Died of chronic renal failure. Possibly
1294
referable to doxorubicin (4.2 mg/kg cumulative dose) administered during
chemotherapy, FIV infection, or concurrent renal disease.
Myocardial failure detected 1300 days following start of chemotherapy;
treated medically, died at home; clinically in remission, no necropsy.
1400
In agreement with previous
Other tumour and patient characteristics, such as anatomical
form (P values range from 0.43 to 0.96), tissue involvement (P
values range from 0.12 to 0.92), histological grade (P = 0.12),
studies of feline LSA, a favourable response to induction with
vincristine, l- asparaginase and prednisolone was strongly
associated with long-term survival; thus, the median survival
period for the 48 cats experiencing a complete remission was
187 days, as opposed to 116 days for the entire cohort of 60
cats. Furthermore, of the 45 cats that went into remission and
for which survival data could be interpreted, 20 were considered
‘long-term survivors’ on the basis of living in excess of 12
months following the initiation of chemotherapy, and the
median survival for this subgroup was >834 days. Considering
the advanced age of many of these cats and the high prevalence
of concurrent diseases (including FIV infection), this probably
corresponds with clinical cure of perhaps 25 to 30% of the
original cohort of cats. In short, response to induction therapy
provided a good indicator of prognosis for cats with LSA.
We believe there should be a rethink about the way survival
statistics are presented to owners of cats with LSA, as the
decision on whether or not to embark on the full course of
multi-agent chemotherapy is best delayed until the initial
response to induction therapy is known. This is because one of
the key prognostic indicators is the response to induction
therapy, that is, whether the patient obtains a complete
remission. Ideally, induction should be achieved using l-
asparaginase (400 to 450 U/kg IM), vincristine (0.025 mg/kg
IV) and prednisolone (2-4 mg/kg PO daily), although l-
asparaginase may be omitted when cost considerations are
limiting. Work done in Australia has shown convincingly that
doxorubicin is unreliable in producing complete remission in
feline LSA,13 in contrast to the situation in the dog.34
FeLV (P = 0.93) status, FIV (P = 0.45) status, breed (P = 0.97), an
d
clinicopathological values (data not shown) all had no significant
association with long-term survival. In summary, clinical and
pathological characteristics of the tumour in a given cat with LSA
were of limited value in predicting long-term survival.
Chemotherapy was generally well tolerated with most cats
showing minor side effects only, principally self-limiting
inappetence and lethargy, typically following administration of
doxorubicin or methotrexate.
Owner satisfaction with chemotherapy
Although only 27 owners responded to the survey, the replies
obtained were representative of both short-term (16
respondents) and long-term (11 respondents) survivor groups.
Although 78% of respondents to the questionnaire were initially
apprehensive or somewhat apprehensive about embarking on
chemotherapy, 85% expressed complete satisfaction with their
decision to pursue this option and 70% believed their cat’s
overall health markedly improved during the first 2 weeks of
treatment (Table 5). Importantly, 78% of owners considered
that chemotherapy required an excessive time commitment on
their part. Although 55% of respondents stated that cost alone
was not a major factor in the decision to proceed with
chemotherapy, only 70% would have opted for treatment had
they been charged $1200 for the first 6 months (rather than the
subsidised cost actually charged). Owners clearly preferred costs
Aust Vet J Vol 79, No 12, December 2001
813

Clinical
Table 3. Effect of patient and tumour characteristics on survival following chemotherapy for
lymphosarcoma.
most cats showing minor side effects
only. Although routine haematological
and biochemical monitoring was not
undertaken, our experience with a small
number of cats supports the contention
of others that doxorubicin may be
nephrotoxic to cats36 (see later). As has
a
Patient or tumour characteristic
Age (median, range; months)
Sex (male: female; %)
Long-term survivors (n =20)
90 (9 to 192)
Short-term survivors (n = 37)
120 (12 to 180)
14:6 (70:30)
24:13 (65:35)
Breed
been reported, cats developed
a
Domestic crossbred
Siamese/Oriental
Non-Siamese purebred
FeLV provirus in tumour
13/20 (65%)
5/20 (25%)
25/37(67%)
8/37(22%)
characteristically soft coat after three to
four months of chemotherapy as a result
of loss of guard hairs; whiskers were shed
also.11,12,15-25
2/20 (10%)
4/37 (11%)
2/12 tumours tested (17%)
9/20 sera tested (45%)
5/28 tumours tested (18%)
20/36 sera tested (56%)
FIV antibody detected by
Western blot analysis
The data from this cohort of Australian
cats suggest there is little or no benefit
from an exhaustive work-up of LSA cases
for ‘staging’, as very few measurable
factors have sufficient impact on
prognosis to make their determination
mandatory. A T-cell phenotype and/or an
age of less than 4-years at diagnosis were
associated with a greater likelihood of
long-term survival. A favourable outcome
for T cell tumours has been reported in
one of the few reports to attempt
correlation of immunophenotype with
outcome.23 However, despite all the
factors considered in this and previous
studies, it is impossible to predict why
individual feline patients responded
Immunophenotype
B-cell
9/20 (45%)
8/20 (40%)
3/20 (15%)
27/37(73%)
6/37 (16%)
4/37 (11%)
T-cell
non-B/non-T
Histological grade
Low
7/20 (35%)
8/20 (40%)
5/20 (25%)
17/37 (46%)
17/37 (46%)
3/37 (8%)
Medium
High
Anatomical type
Mediastinal
3/20 (15%)
7/20 (35%)
4/20 (20%)
5/20 (25%)
5/20 (25%)
3/20 (15%)
3/37(8%)
8/37 (22%)
9/37 (24%)
9/37 (24%)
13/37 (35%)
3/37 (8%)
b
Mediastinal plus nodal
Abdominal
Nodal
favourably
or
unfavourably
to
Mixed
chemotherapy. In particular, we were
unable to determine any common factors
that might have explained why some
cases in all categories did very well with
chemotherapy and were likely cured.
Counter-intuitively, FIV status had no
discernable impact on the response to
chemotherapy. Thus, although FIV may
contribute to lymphomagenesis,5 there is
no evidence that it defines an AIDS-like
stage,5 as FIV-positive cats had similar
survival statistics to FIV-negative cats.
Cases with solitary nodal involvement
were not common, accounting for six
Atypical
Tissue involvement
Mediastinal
Alimentary
Renal
7/20 (35%)
4/20 (20%)
1/20 (5%)
8/37 (22%)
12/37 (32%)
7/37 (19%)
19/37 (51%)
3/37 (8%)
Nodal
10/20 (50%)
1/20 (5%)
Blood
Response to initial chemotherapy
20/20 (100%)
25/37 (68%)
a
3 cases were censored because they could not be confidently placed in either category and a further case
was treated using surgery alone.
b
Mediastinal mass plus involvement of one or more adjacent lymph nodes.
cases in this series. Interestingly, the single case treated using
surgical excision alone was probably cured, as has been
mentioned anecdotally for a similar case in a previous survey of
feline LSA cases.30 Of the cases treated using chemotherapy
alone, only 2 of 5 cats went on to become long-term survivors.
Although we have insufficient data to make firm
recommendations, cats with involvement of a single lymph
node may be best treated surgically, and either monitored, or
given a short cycle of adjuvant chemotherapy; administration of
the full 18-months of multi-agent chemotherapy to these cats is
probably not justifiable on the basis of available information.
Surgery also has a place in the management of some patients
with regional nodal LSA, ocular LSA and in some cats with
alimentary LSA. For example, the cat in the present study that
developed an intussusception around a LSA lesion clearly
required surgical intervention; likewise, surgery is indicated in
cases where perforation of gastrointestinal LSA occurs resulting
in bacterial peritonitis.22
The present work suggests that cats surviving the first 15
weeks of chemotherapy are likely to enjoy robust clinical
remissions. Unfortunately, the present study provides no useful
information to clarify whether on-going maintenance
chemotherapy is required in cats with LSA and it could well be
that not all cats actually require maintenance therapy following
the intensive induction phase of the present protocol.35 More
work needs to be done to address this issue, as the 18-month
chemotherapy protocol used in the present study is very
demanding of both cats and their owners.
It is pleasing that median survival data for the present study
are comparable to those reported from the United States despite
using a slightly altered drug regimen, no routine haematological
monitoring and only fortnightly hospital visits during the
induction period (with administration of cyclophosphamide
and methotrexate PO rather than IV). Despite using slightly
higher than recommended29,35 doses of l-asparaginase and
vincristine, chemotherapy was generally well tolerated, with
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Aust Vet J Vol 79, No 12, December 2001

Clinical
Table 4. Outcome of multi-agent chemotherapy in cats with mediastinal lymphosarcoma.
Two cats developed
acute
toxoplasmosis
during the induction
phase of chemotherapy.
One 7-year-old DSH
with mediastinal LSA
went into remission,
Long-term survivors
Age (months) Survival time
Short-term survivors
Comment(s)
Age (months)
Survival time
(days)
Comment(s)
(days)
> 1271
1294
9
Alive and well
12
146
Died of LSA
11
Renal failure -
doxorubicin?
14
24
112
26
Died of LSA
Died of LSA
however
toxoplasmal
mediastinitis resulted in
dyspnoea and ultimately
death 15 days after
starting chemotherapy.
An 8-year-old DSH
developed toxoplasmal
hepatitis and pancreatitis
28 days after starting
chemotherapy, at a time
when the cat had come
15
22
517
512
Died; diagnosis open
(FeLV-positive)
84
13
Died of toxoplasma
mediastinitis
Hit by truck;
In remission
(cured?)
24
36
> 1405
> 1169
> 538
Alive and well
Alive and well
96
55
Died of LSA
Died of LSA
108
120
168
Lost to follow- up;
cat and owner
relocated to Singapore
120
132
21
37
Died of LSA
Died of LSA
out
of
remission.
T o x o p l a s m o s i s
presumably developed in
these two cats as a result
of recrudescence of a
Table 5. Owner satisfaction with therapy for 27 cats with feline lymphosarcoma.
Question
Answer
Somewhat
quiescent
encysted
focus of
bradyzoites,
Yes
No
(% owners)
(%owners)
(%owners)
presumably as a result of
the immunosuppression
associated with the
1. Was the quality of your cat’s life satisfactory:
a) immediately before chemotherapy?
30
58
52
18
31
26
52
11
22
b) during the first 15 weeks of chemotherapy?
c) after the first 15 weeks of chemotherapy?
administration
prednisolone
of
and
cytotoxic drugs. To the
best of our knowledge,
toxoplasmosis has not
been reported previously
as a complication of
cytotoxic chemotherapy
in the cat, although it has
been reported following
immun osuppressive
2. If your cat was referred to the UVCS, did your regular veterinarian explain
the likely procedures that would be carried out?
50
15
35
3. Were the costs quoted maintained within reasonable limits?
4. Were you apprehensive about your cat undergoing chemotherapy?
5. Were the possible side effects of chemotherapy explained adequately?
93
41
93
70
7
37
0
0
22
7
6. Was there a marked improvement of your cat’s condition within 2 weeks
of commencing chemotherapy?
15
15
7. Was cost a major factor in deciding to go ahead with chemotherapy?
8. Was chemotherapy too time consuming?
19
78
26
18
55
4
therapy
for
severe
bowel
inflammatory
9. Would you consider chemotherapy if the cost was:
disease.37 Perhaps the
a) $1200 over 6 months
70
18
26
27
4
higher
doses
of
b) $1200 in one initial payment
55
prednisolone used in the
present chemotherapy
protocol was responsible
for this phenomenon.
We chose to use twice
the usual recommended
dose of prednisolone as
part of the induction
10. Were you satisfied with the service that you received at the UVCS
during chemotherapy
100
85
0
0
3
11. Looking back over the chemotherapy of your cat, are you now glad
that you attempted treatment?
12
Please feel free to make any additional comments in the space provided overa
aowners were given space to write additional comments on the back of the questionnaire sheet.
protocol, as many authorities recommend using 4 mg/kg
prednisolone daily for treating feline immune-mediated
disease38 (twice the dose commonly recommended for dogs), so
it was hoped these higher doses would similarly have improved
efficacy in treatment of LSA over doses recommended previously
(typically 2 mg/kg daily). Alternatively, toxoplasmosis may be
more of a risk in the Australian setting than in North America,
because feeding of fresh meat (including kangaroo) is much
more commonplace here. There may be some justification in the
prophylactic treatment of cats receiving chemotherapy to
minimise the risk of recrudescent toxoplasmosis, using either
trimethoprim/sulfonamide preparations or clindamycin. Other
opportunistic pathogens have been described as a cause of
morbidity or mortality in cats being given chemotherapy for
13
LSA, including Salmonella species,24 Cryptococcus neoformans
and Mycobacterium avium complex.39
There seems to be a consensus in the recent literature that the
addition of doxorubicin to protocols utilising vincristine and
cyclophosphamide has extended the median survival time in cats
with LSA given sequential multi-agent chemotherapy.21-24 The
median survival times and proportion of long-term survivors
observed in the present study are in accord with this
Aust Vet J Vol 79, No 12, December 2001
815

Clinical
observation. However, two cats treated using the present
protocol developed renal failure during or after the course of
chemotherapy, and it is possible that doxorubicin contributed to
the deterioration of renal function in these cats. In one cat, a 7-
year-old-male DSH, with regional multinodal involvement,
marginal azotaemia was present initially (urea 15 mmol/L
[reference range < 11 mmol/L]; creatinine 190 µmol/L [reference
range < 180 µmol/L]); inappetance and weight loss that
developed 146 days after starting therapy was shown to be
referable to worsening azotaemia. The second cat, an 11-month-
old Siamese, had been treated successfully for mediastinal LSA,
but developed renal failure 3.6 years after starting therapy; the
baseline urea and creatinine concentrations in this patient were
within reference ranges prior to therapy. These two cat had
received cumulative doxorubicin doses of 3.1 and 4.2 mg/kg,
respectively. Also, a 3-year-old cat treated for abdominal LSA
developed myocardial failure 4-years after starting treatment for
LSA, the cat having received a cumulative doxorubicin dose of
4.2 mg/kg . Echocardiography demonstrated reduced myocardial
contractility, normal left ventricular and septal dimensions and
left atrial dilatation. Although the myocardial dysfunction in this
cat may have been related to primary myocardial disease or
myocarditis, the possibility that the observed changes were
referable to doxorubicin should be considered, even though
experimental work suggests this agent is less cardiotoxic in the cat
than in the dog.40 As a result of these concerns in relation to
doxorubicin, the authors now recommend that no more than 3
mg/kg of doxorubicin be given cumulatively to cats as part of a
LSA chemotherapy protocol and that urea and creatinine
concentrations be determined prior to administering each dose of
doxorubicin. Some workers suggest that old cats with pre-existing
renal disease are particularly vulnerable to the nephrotoxic effects
of doxorubicin and may benefit from saline diuresis prior to
administration of the drug.40
All cats in the present study received l-asparaginase on two
occasions as part of the chemotherapy regimen. Although this
agent is used commonly in both canine and feline LSA
chemotherapy protocols, it is not commonly used to treat
human patients with lymphoma. More work is required to
determine the contribution of this drug to the efficacy of the
present drug regimen, as currently this agent represents the most
expensive component of therapy, especially in practices where it
is not possible to spread the cost of a vial over several feline
patients. A prospective study comparing the present protocol (or
a similar one), with and without the inclusion of l-asparaginase,
should readily resolve this issue.
An interesting and important finding of the present study was
that young cats with LSA were more likely to be long-term
survivors. This has not been well documented previously and
may reflect the tendency for young cats with genetically-
transmitted mediastinal LSA to account for the majority of cases
in cats less than 4-years-of-age.13 Mediastinal LSA accounted for
all but one of the cases less than 4 years-of-age, the other being a
DSH cat with abdominal (renal and alimentary) LSA that was
cured using chemotherapy. Table 4 shows that survival in cats
with mediastinal LSA was correlated with young age at time of
diagnosis. Whatever the underlying basis, youth per se would
appear to be a positive prognostic indicator in cats treated for
LSA.
Indeed, most of the responding owners took the time to write
additional comments on the questionnaire, all of which were
positive endorsements of the experience. Interestingly, a number
of owners volunteered that helping the cause of veterinary
medicine was a motivating factor for including their cats in this
study. The chemotherapy protocol we used required biweekly
visits for 15 weeks, followed by monthly visits until 18 months
after starting the protocol; clearly this was a substantial
commitment for the owners, as reflected by their comments in
relation to the time-consuming nature of therapy. This may be
less of an issue for private practitioners conducting
chemotherapy close to the owners place of residence, and where
chemotherapy can be done at a more convenient time (such as
weekends). Further, the ability to use sevoflurane14 to
immobilise cats rapidly and reversibly for chemotherapy has
substantially improved the speed and readiness with which IV
chemotherapy can be conducted; this may make the process of
out-patient chemotherapy even more convenient for owners and
the veterinary team. Overall, the results of the survey suggest
that when confronted with a reasonably priced chemotherapy
protocol, most well-motivated owners found the results of
therapy rewarding, irrespective of the survival time of the
individual cat. Although cats occasionally appeared to be unwell
for a few days following dosing with cytotoxic drugs (especially
doxorubicin), on the whole they did well constitutionally. Two
cats inexplicably became lethargic, lost weight and had poor
appetite and vigour during chemotherapy. It was not determined
whether these cats had occult recurrent LSA, intercurrent disease
(such as pancreatitis) or were suffering an AIDS-like phase of
FIV infection. Necropsies were not permitted on these ‘fading’
cats to decide between these possibilities. Anecdotally, cats
destined to be long-term survivors tended to do very well from
the start during multi-agent chemotherapy, whereas cats
destined to come out of remission, or develop complications or a
wasting syndrome often had problems referable to the drug
regimen right from the start. Thus, a common sense approach
on the part of both the owner and the veterinary team should
readily decide which cats deserve on-going chemotherapy based
on the clinical status of the cat. Finally, a stable or increasing
body weight was a reliable sign that the patient was doing well
and remained in remission.
Acknowledgments
The authors thank the many veterinarians who provided clinical
material for this study. The project was supported by a grant from
the Australian Companion Animal Health Foundation. L Gabor
was the recipient of an FH Loxton Fellowship and a Goldia and
Susie Lesue Fellowship. R Malik was supported by the Valentine
Charlton Bequest of the Post Graduate Foundation of Veterinary
Science of The University of Sydney. The IDEXX Company
kindly donated the ELISA kits and Dr J Beatty, a Wellcome Fellow,
kindly provided Witness tests.
References
1. Gabor LJ, Malik R, Canfield PJ. Clinical and anatomical features of
lymphosarcoma in 118 cats in Sydney. Aust Vet J 1998;76:725-732.
2. Gabor LJ, Canfield PJ, Malik R. Immunophenotypical and histological
characterisation of 109 cases of feline lymphosarcoma. Aust Vet J 1999;77:436-441.
3. Gabor LJ, Canfield PJ, Malik R. Haematological and biochemical changes in
cats with naturally occurring lymphosarcoma. Aust Vet J 2000;78:456-461.
4. Gabor LJ, Jackson ML, Trask B et al. Feline leukaemia virus status of
Australian cats with lymphosarcoma. Aust Vet J 2001;79:476-481.
5. Gabor LJ, Love DN, Malik R, Canfield PJ. Feline immunodeficiency virus
status of Australian cats with lymphosarcoma. Aust Vet J 2001;79:540-545.
6. Jarrett WFH, Crighton GW, Dalton RG et al. Leukaemia and lymphosarcoma
Finally, the results of the owner survey and our impression as
clinicians suggested that cats generally coped well with the
chemotherapy protocol and enjoyed a good quality of life.
816
Aust Vet J Vol 79, No 12, December 2001

Clinical
in animals and man. I- lymphosarcoma or leukaemia in the domestic animals.
Vet Rec 1966;79:693-699.
7. Hardy WD Jr. Haematopoietic tumours of cats. J Am Anim Hosp Assoc
1981;17: 921-940.
association with prognosis in 90 cats. J Vet Intern Med 1998;12:349- 354.
24. Mauldin GE, Mooney SC, Meleo KA, et al Chemotherapy in 132 cats with
lymphoma: 1988-1994 (abstract) In: Proc Vet Cancer Soc 15th Annu Conf 1995;
35-36.
8. Couto C, Hammer A. Oncology. In: Sherding RG, ed. The cat. Diseases and
clinical management. 2nd edn. Churchill Livingstone, New York, 1994: 755-818.
9. Auer L, Bell K. The AB blood group system of cats. Anim Blood Groups and
Biochem Genet 1981;4:287-297.
10. Malik R, Kendall K, Cridland J et al. Prevalences of feline leukaemia virus
and feline immunodeficiency virus infection in cats in Sydney. Aust Vet J
1997;75: 43-47.
25. Rassnick KM, Mauldin GN, Moroff SD et al. Prognostic value of argyrophilic
nucleolar organizer region (AgNOR) staining in feline intestinal lymphoma. J Vet
Int Med 1999;13:187-190.
26. Aisenberg AC. Coherent view of non-Hodgkin’s lymphoma. J Clin Oncol
1995;13:2656-2675.
27. Grogan TM, Miller TP. Immunobiologic correlates of prognosis in lymphoma.
Seminars in Oncology 1993:20;58-74.
11. Cotter SM. Treatment of lymphoma and leukaemia with cyclophosphamide,
vincristine and prednisolone: II. Treatment of cats. J Am Anim Hosp Assoc
1983;19:166-172.
28. Keller ET, MacEwen EG, Rosenthal RC, et al. Evaluation of prognostic
factors and sequential combination chemotherapy with doxorubicin for canine
lymphoma. J Vet Int Med 1993; 7:289-295.
12. Jeglum KA, Whereat A, Young K. Chemotherapy of lymphoma in 75 cats. J
Am Vet Med Assoc 1987;190:174- 178.
13. Peaston AE, Maddison JE. Efficacy of doxorubicin as an induction agent for
cats with lymphosarcoma. Aust Vet J 1999;77:442-444.
14. Tzannes S, Govendir M, Zaki S et al. The use of sevoflurane in a 2:1 mixture
of nitrous oxide and oxygen for rapid mask induction of anaesthesia in the cat. J
Fel Med Surg 2000;2:83-90.
15. Mooney SC, Hayes AA, Matus RE, MacEwen EG. Renal lymphoma in cats:
28 cases (1977-1984). J Am Vet Med Assoc 1987;191:1473-1477.
16. Mooney SC, Hayes AA, MacEwan EG et al. Treatment and prognostic
factors in lymphoma in cats: 103 cases (1977-1981). J Am Vet Med Assoc
1989;194:696-699.
17. Elmslie RE, Ogilvie GK, Gillette EL, McChesney-Gillette S. Radiotherapy
with and without chemotherapy for localized lymphoma in 10 cats. Vet Radiol
1991:32:277-280.
18. Spodnick GJ, Berg J, Moore FM, Cotter SM. Spinal lymphoma in cats: 21
cases (1976-1989). J Am Vet Med Assoc 1992;200:373-376.
19. Lane SB, Kornegay JN, Duncan JR, Oliver JE. Feline spinal
lymphosarcoma: a retrospective evaluation of 23 cats. J Vet Intern Med
1994;8:99-104.
20. Mahony OM, Moore AS, Cotter SM et al. Alimentary lymphoma in cats: 28
cases (1988-1993). J Am Vet Med Assoc 1995;207:1593-1598.
21. Moore AS, Cotter SM, Frimberger AE et al. A comparison of doxorubicin and
COP for maintenance of remission in cats with lymphoma. J Vet Int Med
1996;10:372-375.
29. Matus RE. Chemotherapy of lymphoma and leukaemia. In: Kirk RW ed.
Current veterinary therapy X: small animal practice. Saunders, Philadelphia
1989;482-488.
30. Valli VE, Jacobs RM, NorrisA, et al. The histologic classification of 602 cases
of feline lymphoproliferative disease using the National Cancer Institute working
formulation. J Vet Diagn Invest 2000;12:295-306.
31. Lorimer HE. Hereditary lymphosarcoma in Oriental Shorthair cats. Feline
Pract Suppl 1999:29.
32. Hahn KA, Frazier DL, Cox CK, Legendre AM. Effect of infusion regime on
doxorubicin pharmacokinetics in the cat. J Am Anim Hosp Assoc 1997;33:427-433.
33. Valerius KD, Ogilvie GK, Fettman MJ, et al. Comparison of the effects of
asparaginase administered subcutaneously versus intramuscularly for treatment
of multicentric lymphoma in dogs receiving doxorubicin. J Am Vet Med Assoc
1999;214: 353-356.
34. Carter RF, Harris CK, Withrow SJ et al. Chemotherapy for canine lymphoma
with histopathological correlation: doxorubicin alone compared with COP as first
treatment regimen. J Am Anim Hosp Assoc 1987;23:587-596.
35. Moore AS. Treatment of feline lymphoma. Fel Pract 1996;24:17-20.
36. Cotter SM, Kanki PJ, Simon M. Renal disease in five tumor-bearing cats
treated with Adriamycin. J Am Anim Hosp Assoc 1985;21:405-409.
37. Petersen JL, Willard MD, Lees GE et al. Toxoplasmosis in two cats with
inflammatory intestinal disease. J Am Vet Med Assoc 1991;199:473-476.
38. Thompson JP. Disorders of the immune system. In: Sherding RG, ed. The
Cat. Diseases and clinical management. 2nd edn, Churchill Livingstone, New
York 1994; 685
22. Zwahlen CH, Lucroy MD, Kraegel SA, Madewell BR. Results of
chemotherapy for cats with alimentary malignant lymphoma: 21 cases (1993-
1997). J Am Vet Med Assoc 1998;213:1144-1149.
23. Vail DM, Moore AS, Ogilvie GK, Volk LM. Feline lymphoma (145 cases):
proliferation indices, cluster of differentiation 3 immunoreactivity, and their
39. Malik R, Gabor LJ, Martin P et al. Subcutaneous granuloma caused by
Mycobacterium avium complex infection in a cat. Aust Vet J 1998; 76: 604-607.
40. O’Keefe DA, Sisson, DD, Gelberg HB et al. Systemic toxicity associated with
doxorubicin administration to cats. J Vet Int Med 1993;7:309-317.
(Accepted for publication 20 June 2001)
Laryngeal rhabdomyoma in a dog
a
b
c
AJ O’HARA, M MCCONNELL , K WYATT and C HUXTABLE
Division of Veterinary and Biomedical Science, Murdoch University, Murdoch, Western Australia 6150
Email: aohara@central.murdoch.edu.au
to report the clinico-pathological presentation of a laryngeal
A 4-year-old spayed female Golden Retriever was presented
for investigation of progressive loss of bark, continuous
panting and increased upper respiratory noise. Examination
of the larynx and pharynx under general anaesthesia
identified a spherical 5 x 3 cm mass involving the right
arytenoid cartilage. Cytological examination of fine needle
aspirates from the mass suggested the tumour was a
carcinoma, however histological examination in association
with immunoperoxidase and histochemical staining identified
the mass as a laryngeal rhabdomyoma.
rhabdomyoma in a dog and demonstrate the value of
immunoperoxidase and histochemical staining in the diagnosis
of these tumours.
Case report
A 4-year-old spayed female Golden Retriever was referred to
the Murdoch University Veterinary Hospital for investigation of
progressive loss of bark, continuous panting and increased
upper respiratory noise. Clinical examination identified mild
left submandibular lymphadenomegaly, bilateral loud harsh
breath sounds over the chest and along the length of the
trachea, and discomfort on palpation of the larynx. A complete
blood count and biochemical profile demonstrated only mild
Aust Vet J 2001;79:817-821
Key words: Larynx, rhabdomyoma, dog, neoplasia, cytology, desmin, myoglobin
he cytological diagnosis of rhabdomyoma is difficult
when the aspirated cells lack cross striations and there is
a
VETPATH Laboratory Services, PO Box 18, Belmont, Western Australia 6984
Murdoch Animal Cancer Care Unit, Division of Veterinary and Biomedical
T
a predominance of round/polygonal cells. Desmin and
b
myoglobin immunohistochemistry plus ultrastructural
examination are required to confirm the diagnosis if routine
light microscopy is not definitive. The purpose of this paper is
Science, Murdoch University, Murdoch, Western Australia 6150
c
Department of Biomedical Science, College of Veterinary Medicine, Cornell
University, Ithaca, NY 14853, USA
Aust Vet J Vol 79, No 12, December 2001
817