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Feline Renal Lymphoma Incidence Study

This study investigates the incidence, clinical signs, treatment, and survival outcomes of renal lymphoma in cats, analyzing data from 740 lymphoma cases over a nine-year period. The incidence of renal lymphoma was found to be 3.6%, with median survival times differing between treatment protocols, though no predictive factors for survival were identified. The authors conclude that further prospective studies are needed to determine optimal chemotherapy protocols for renal lymphoma in cats.

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0% found this document useful (0 votes)
15 views9 pages

Feline Renal Lymphoma Incidence Study

This study investigates the incidence, clinical signs, treatment, and survival outcomes of renal lymphoma in cats, analyzing data from 740 lymphoma cases over a nine-year period. The incidence of renal lymphoma was found to be 3.6%, with median survival times differing between treatment protocols, though no predictive factors for survival were identified. The authors conclude that further prospective studies are needed to determine optimal chemotherapy protocols for renal lymphoma in cats.

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mvz.ramon.erh
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd

984363 JFM Journal of Feline Medicine and SurgeryWilliams et al

Original Article

Journal of Feline Medicine and Surgery

Incidence and treatment of feline 1­–9


© The Author(s) 2021
Article reuse guidelines:
renal lymphoma: 27 cases sagepub.com/journals-permissions
DOI: 10.1177/1098612X20984363
https://doi.org/10.1177/1098612X20984363
journals.sagepub.com/home/jfm
This paper was handled and processed
by the American Editorial Office (AAFP)
for publication in JFMS
Ashlyn G Williams1 , Ann E Hohenhaus1
and Kenneth E Lamb2

Abstract
Objectives   Lymphoma is the most common feline hematopoietic malignancy. Incidence of renal lymphoma has
not been reported as a subset of a large population of feline lymphoma cases. Previous studies have reported
renal lymphoma as both a singular entity as well as a component of multicentric disease. The clinical presentation,
diagnostic evaluation, therapy and outcomes related to renal lymphoma have not been reported since Mooney et al
in 1987. This retrospective study aimed to describe the incidence of renal lymphoma, clinical signs, treatment and
survival.
Methods   Using a database of cats diagnosed with lymphoma between January 2008 and October 2017, cats
with renal lymphoma were selected for further analysis. Cases were retrospectively staged according to Mooney
et al (1987) and Gabor et al (1998). Data collected included age, clinical signs, clinicopathologic data, diagnostic
imaging findings, lymphoma diagnostic method(s), treatment protocol(s) and survival time. Analyses comparing
median survival based on therapy administered, renal lymphoma vs multicentric lymphoma, central nervous system
involvement, presence of azotemia, anemia and International Renal Interest Society (IRIS) stage at diagnosis were
performed.
Results   From a population of 740 cats with lymphoma, 27 cats had renal lymphoma (incidence, 3.6%), and 14 of
those cats had multicentric lymphoma. Fewer stage IV and V cases were identified in this data set compared with
Mooney et al; however, not all cats were completely staged. Median survival (range) for cats receiving corticosteroids
alone compared with those receiving an L-CHOP (L-asparaginase, vincristine, cyclophosphamide, doxorubicin,
prednisolone)-based protocol was 50 days (20–1027 days) in the corticosteroid group and 203 days (44–2364
days) for the L-CHOP group (P = 0.753) for cats that died secondary to lymphoma.
Conclusions and relevance   Neither clinical stage nor other factors were predictive of survival. Prospective studies
are required to determine the optimal chemotherapy protocol.

Keywords: Lymphoma; incidence; renal; azotemia; reverse stage migration

Accepted: 6 December 2020

Introduction
Lymphoma is the most common hematopoietic malig- The goals of this study were to retrospectively apply
nancy in cats and is the most common neoplasm reported two staging systems for renal lymphoma in cats to this
in the kidney of cats.1 The incidence of renal lymphoma population of cats and to describe the incidence, clinical
has been reported to range from 7–30% in studies of signs, treatment and outcomes in cats with renal lym-
approximately 100 cats each.2–5 The clinical presentation, phoma. The secondary aim was to evaluate prognostic
results of a diagnostic work-up, therapy and outcomes
related specifically to renal lymphoma have not been
reported since Mooney et al in 1987.1 Since that time, 1The Cancer Institute, Animal Medical Center, New York, NY, USA
advances in diagnostics, such as the widespread use 2Lamb Statistical Consulting, West St Paul, MN, USA
of abdominal ultrasound, have improved the ability to
Corresponding author:
detect changes concerning for neoplastic infiltration and Ashlyn G Williams, DVM, Animal Cancer Care Clinic, 1122 NE 4th
may have resulted in stage migration in feline lymphoma, Avenue, Fort Lauderdale, FL 33304, USA
as has been reported in canine multicentric lymphoma.6 Email: [email protected]
2 Journal of Feline Medicine and Surgery 

factors in renal lymphoma including International Renal Table 1 Animal Medical Center staging system1
Interest Society (IRIS) stage, presence of azotemia and
anemia at diagnosis and evidence of multicentric disease Stage Organ/tissue involvement
at diagnosis. I Single tumor (extranodal) or anatomic area
Our primary hypothesis was that renal lymphoma (nodal)
occurs both as a singular entity within the kidneys and II Two tumors (extranodal), two or more nodal
also as a component of multicentric disease. Our sec- areas on same side of the diaphragm, primary
ondary hypothesis was that the presence of azotemia or resectable gastrointestinal tumor
anemia, diagnosis of multicentric disease, stage of dis- III Two tumors (extranodal) on opposite sides of
ease and type of treatment pursued would significantly the diaphragm, unresectable intra-abdominal
disease, paraspinal or epidural tumors
impact survival. The authors also hypothesized that
IV Stage I–III with liver or spleen involvement
the decrease in the prevalence of feline leukemia virus
V Stage I–IV with central nervous system or bone
(FeLV)-positive cats since 1987 would have an impact on marrow involvement
response to therapy and survival.

Materials and methods


The pathology database of the Animal Medical Center Table 2 Gabor staging system2
(AMC) was searched from January 2008 to October 2017
Anatomical Subcategory Organ/tissue
for cats with a lymphoma diagnosis obtained via cytol- category involvement
ogy or histopathology. Renal lymphoma was defined as
large cell lymphoma in the kidney(s) diagnosed via cytol- Mediastinal Any structure within the
ogy by a board-certified pathologist. Multicentric disease mediastinal space
was defined as large cell lymphoma in the kidney(s) and Abdominal Alimentary GI tract and associated
lymph nodes, excluding
other organs diagnosed via cytology by a board-certified
liver and pancreas
pathologist. Cats diagnosed with large granular lympho- Renal Either or both kidneys
cyte lymphoma were included in the large cell lymphoma Other Organs (liver, spleen)
group. Medical records of cats diagnosed with renal in the absence of GI or
lymphoma were reviewed. Data collected included age, renal involvement
clinical signs, clinicopathologic abnormalities, diagnostic Combination Combination(s) of
imaging abnormalities, diagnostic method(s), treatment the above three
protocol(s) and survival time. subcategories
Prognostic factors for survival (when available), Nodal One or more peripheral
lymph nodes
including IRIS stage, presence of azotemia or anemia
Solitary One peripheral lymph
at diagnosis and evidence of multicentric disease, were
node only
evaluated. Anemia was defined as a hematocrit below
Regional A chain of adjacent
28.2% at diagnosis. Azotemia was defined as a blood lymph nodes in a
urea nitrogen (BUN) greater than 27 mg/dl or a creati- restricted anatomical
nine greater than 1.6 mg/dl. The designated value for region
anemia was selected due to this being the lower end of Multinodal Many or all peripheral
the reference interval for IDEXX reference laboratories, lymph nodes
which provided laboratory testing in these patients. The Atypical Non-lymphoid tissues
high end of the reference interval for BUN and creatinine such as the CNS, skin,
larynx, nasal cavity
are 27 mg/dl and 1.6 mg/dl, respectively. IRIS guidelines
Mixed Combination of two
for creatinine were used to categorize cats by IRIS stage.
or more of the above
Cases were retrospectively staged according to categories
Mooney et al1 and Gabor et al.2 The AMC staging system
is outlined in Table 1. The Gabor staging system is out- GI = gastrointestinal; CNS = central nervous system
lined in Table 2.
Screening for comorbidities was based on avail-
ability of clinical pathologic data, thoracic radiographs Statistical methods
and abdominal ultrasound. Chemotherapy toxicity Baseline descriptive statistics are reported as mean and
was retrospectively graded according to the Veterinary standard deviation for normally distributed variables
Co-operative Oncology Group’s Common Terminology and median and interquartile range for non-normally
Criteria for Adverse Events (VCOG-CTCAE).7 distributed variables. The distribution of error residuals
Williams et al 3

derived from general linear models were assessed by


visual inspection followed by the Kolmogorov–Smirnoff
test. Between-groups analyses of baseline variables were
performed using analysis of variance, as error residu-
als were normally distributed. Analyses for proportions
of categorical variables were evaluated with a χ2 test or
Fisher’s exact analysis as appropriate. Date of study entry
was the time from date of diagnosis with renal lymphoma
while end date was date of death. Time-to-event analyses
were carried out in univariate by way of Kaplan–Meier
product limit estimates. Statistical differences between
Kaplan–Meier product limit estimates strata were deter-
mined by a log-rank test. Time-to-event survival time
analyses represented time from study entry to end date.
Cases lost to follow-up, dead from causes other than lym-
phoma or remaining alive were right censored. Analyses Figure 1 Fine-needle aspiration cytology of renal lymphoma
were performed with statistical software (SAS 9.3, Cary in a cat. In addition to the monomorphic population of large
NC 2016) where P <0.05 was deemed significant. lymphocytes, a renal tubule can be seen on the lower left of
Event-free survival was defined as the time interval the image and a glomerulus in the upper right. Magnification
X 20. Wright-Giemsa. Courtesy of Dr Michael Wiseman,
from the date of diagnosis with renal lymphoma to the
IDEXX Laboratories
date of death. Patients with an unavailable date of death
were considered lost to follow-up at date of last contact
and censored. Pre-treatment hematology results were available for
26 cats and biochemical profile results were available for
Results 27 cats. The most common hematologic abnormality was
Review of the AMC pathology databases identified 740 anemia (17/26 cats). Other hematologic abnormalities
cats with a diagnosis of lymphoma based on histology included thrombocytopenia, leukocytosis, neutrophilia,
or cytology interpreted by a board-certified patholo- monocytosis and lymphopenia. Serum biochemical
gist. Of these cases, 121 cats had a diagnosis of large cell abnormalities included azotemia (17/26 cats), hypoal-
lymphoma confirmed by cytology. Twenty-seven of 121 buminemia (5/26 cats), hypercalcemia (1/26 cats) and
cats diagnosed with large cell lymphoma were found to elevated alkaline phosphatase (1/26 cats). Pre-treatment
have renal lymphoma based on renal aspiration cytology, BUN was available in all 27 cats and creatinine was avail-
making the incidence of renal lymphoma in this popula- able in 16 cats. Thirteen cats had elevated BUN and/
tion 3.6% of all cats with lymphoma and 22.3% of cats or creatinine. Pre-treatment urine specific gravity was
with large cell lymphoma. Thirteen cats were found to available in 11 cats. All 11 cats were diagnosed with renal
have renal lymphoma only and 14 cats were found to azotemia. Two cats were categorized as stage 1, three cats
have multicentric lymphoma. One cat had evidence of as stage 2, two cats as stage 3 and four cats as stage 4
central nervous system (CNS) involvement, which was according to IRIS. Retroviral testing results were available
confirmed with MRI and cytology of the cerebrospinal for five cats. One cat was feline immunodeficiency virus
fluid. One cat with renal lymphoma and sternal lym- (FIV) positive and FeLV negative. The remaining four cats
phadenopathy and a diagnosis of large granular lympho- were FIV and FeLV negative.
cyte lymphoma was included in the large cell lymphoma Diagnostic imaging results were available for all 27
group because of similar outcomes between large cell cats. Abdominal ultrasound was performed in all cats,
lymphoma and large granular lymphoma.8–10 Figure 1 is with the most common ultrasonographic abnormality
a photomicrograph of a fine-needle aspiration cytology being renomegaly (27/27 cats). Other abnormal ultra-
sample from a feline patient with renal lymphoma. Figure 2 sound findings are included in Table 3. Fine-needle aspi-
illustrates case selection. ration was performed on the liver and spleen in all cats
The mean age of the cats included was 7.67 years with ultrasonographic abnormalities of these organs but
(range, 1–18 years; median 11 years). Seventeen were cas- not in cats with a normal appearance of these organs on
trated males and 10 were spayed females. There were 24 ultrasound. Results of fine-needle aspiration cytology
domestic shorthair cats, two domestic longhair cats and performed in abdominal organs are outlined below in
two Maine Coon cats. The most commonly reported clini- Table 3. Thoracic radiographs were available in 19 cats.
cal sign at presentation was anorexia (9/27 cats). Other Radiographic findings are summarized in Table 4. Results
clinical signs included weight loss, polyuria, polydipsia, of fine-needle aspiration cytology of pleural effusion and
pollakiuria, lethargy, hyporexia, dyspnea and hematuria. sternal lymphadenopathy are included in Table 4. Table 5
4 Journal of Feline Medicine and Surgery 

Figure 2 Feline lymphoma diagnoses from the Animal Medical Center between January 2008 and October 2017

illustrates the AMC staging system from Mooney et al1 treated with chemotherapy received steroids orally for
compared with the current study. the duration of their chemotherapy protocol. The most
Each patient was staged according to clinical find- common chemotherapy protocol was a combination
ings using the previously described staging systems.1,2 of L–CHOP, which was administered to nine cats. The
Twenty-four cats were placed in the abdominal stage and L-CHOP protocol utilized is outlined below in Table 6. The
three in the mixed stage based on the Gabor staging sys- cat with large granular lymphocyte lymphoma received
tem. Table 5 compares the staging of cats in the present cytosine arabinoside as a single agent. Five cats received
study and the prior study using the AMC staging system. chemotherapy but had an unknown treatment protocol
Twenty-four cats underwent treatment for lymphoma. owing to incomplete medical records. Nine cats were
Fifteen cats were treated with chemotherapy. All cats treated with corticosteroids alone. Radiation therapy was
Williams et al 5

Table 3 Abdominal ultrasound abnormalities Table 6 L-CHOP chemotherapy protocol

Ultrasound Number Cytology findings Week Drug Dose Route of


abnormalities of cats administration

Renomegaly 27 Large cell 0 L-asparaginase 400 IU/kg IM


lymphoma (27) 1 Vincristine 0.5 mg/m2 IV
Renal subcapsular 5 Large cell 2 Cyclophosphamide 200 mg/m2 IV
edema lymphoma (5) 3 Vincristine 0.5 mg/m2 IV
Intestinal mass(es) 13 Large cell 4 Doxorubicin 1 mg/kg IV
lymphoma (13)
Bladder wall thickening 1 Corticosteroids administered at 1–2 mg/kg daily according to clinician
Muscularis thickening 1 preference
Segmental enteropathy 1
Pancreatitis 2
Ascites 3
Hyperechoic liver 2 Large cell
lymphoma (1)
Hepatic lipidosis (1)
Hepatomegaly 1 Large cell
lymphoma
Peritonitis/retroperitonitis 1
Lymphadenopathy 5 Large cell
lymphoma (5)

Table 4 Thoracic radiograph findings

Thoracic radiograph Number Cytology findings


findings of cats Figure 3 Survival of cats treated with L-CHOP (blue line)
Normal thorax 13 compared with cats treated with corticosteroids alone (red line)
Pleural effusion 1 Large cell lymphoma
Pneumonia 4 protocols included a MOPP (mechlorethamine, vincris-
Cardiomegaly 3 tine, procarbazine, prednisolone) protocol and single-
Sternal lymphadenopathy 1 Large cell lymphoma agent lomustine. Radiation therapy was administered to
the brain and spinal cord of one cat diagnosed with CNS
lymphoma at relapse. Survival was known in nine cats
Table 5 Animal Medical Center staging system results treated with corticosteroids alone and nine cats treated
from Mooney et al1 compared with the current study with an L-CHOP chemotherapy protocol. The median
survival in cats treated with an L-CHOP-based chemo-
Mooney et al1 Current study
therapy protocol was 203 days, which was not statisti-
Number of cats* Number of cats†
cally significant when compared with cats treated with
Stage I 0 0 corticosteroids alone (median survival 42 days, P value
Stage II 11 13 = 0.0753). Figure 3 compares survival of cats treated with
Stage III 5 10 L-CHOP and cats treated with steroids.
Stage IV 6 2 Weeks 1–4 were repeated four times, initially at a 7-day
Stage V 5‡ 1§ interval with a 1-week break after the first two cycles,
*No abdominal ultrasounds performed
then the treatment interval was extended to 14 days for
†19/27 thoracic radiographs performed the final two cycles.
‡8/28 cats underwent bone marrow aspiration
Adequate medical records for grading chemotherapy
§1/27 cats underwent MRI/cerebrospinal fluid tap, no cats underwent
toxicity were available in 10/27 patients. Chemotherapy
bone marrow aspiration
toxicity was typically mild with the most common effect
being loose stool. Vincristine administration was associ-
administered to the brain of the stage V cat with CNS ated with the most adverse effects including grade 1 vom-
involvement in addition to L-CHOP chemotherapy. iting in one cat, grade 1 diarrhea in three cats and grade 2
Three cats received rescue protocols after treatment lethargy in two cats. One cat developed grade 3 lethargy
failure with an L-CHOP chemotherapy protocol. Rescue following mechlorethamine administration. No other
6 Journal of Feline Medicine and Surgery 

grade 3 or 4 toxicities were reported. Gastrointestinal data set appears to identify an increase in the incidence
signs were commonly mild and managed at home with of renal lymphoma in the AMC feline population over the
supportive medications (maropitant [Cerenia; Zoetis], past three decades.5
ondansetron, metronidazole). Stage has had variable impact on survival and response
Cats with renal lymphoma as a singular entity within to therapy in the literature on feline lymphoma. 1,4,13
the kidneys had a median survival of 50 days. The dif- Neither staging system evaluated predicted outcome in
ference between the two groups was not statistically this group of cats, potentially owing to the small number
significant (P = 0.8428). Azotemia at diagnosis was not of cases or lack of complete staging in the cats included
found to have a significant impact on survival (median in this and previous studies; however, the authors also
75 days in azotemic cats, 47 days in non-azotemic believe there are likely inherent problems with the two
cats, P = 0.4100). Anemia at diagnosis also had no sig- staging systems. Tumor staging serves the purpose of
nificant impact on survival (median 44 days in anemic identifying patients with increasing tumor burden and
cats, 86 days in non-anemic cats, P = 0.1735). Cats with determining prognosis from that information. The Gabor
stage II disease had a median survival of 97 days and staging system provides an anatomic description of
cats with stage III disease had a median survival of tumor location, which would not be expected to correlate
45 days, which was not statistically different (P = 0.6595). with tumor burden.2 The AMC staging system attempts
A median survival could not be calculated for the cats to define increasing tumor burden with increasing stage
in the remaining stages due to low case numbers. Cats by having higher stages correlate with disease identified
within the abdominal stage had a median survival of in an increasing number of anatomic sites.1 Despite the
50 days and cats in the mixed stage had a median sur- cats included in this study not receiving full staging, the
vival of 114.5 days, which was not statistically significant authors feel that the staging that was performed is reflec-
(P = 0.9586). tive of the typical clinical staging performed in cats with
The primary cause of death in 22 of the 27 cats was lymphoma. The cats included in the Mooney et al1 manu-
lymphoma. Four cats died of causes other than lym- script had no abdominal ultrasounds performed and only
phoma. The first cat died of a second malignancy, oral eight of 28 cats had bone marrow aspirates performed.
squamous cell carcinoma, 2639 days post diagnosis. This The cats included in Gabor et al2 only had thoracic radio-
cat was treated with an L-CHOP chemotherapy protocol. graphs performed if dyspneic or if the heart was in an
The second cat was euthanized secondary to neurologic abnormal location based on physical examination find-
disease with no evidence of recurrent lymphoma based ings. Abdominal ultrasound was also not performed in
on complete blood count (CBC), biochemical profile, tho- all cats in Gabor et al.2
racic radiographs, abdominal ultrasound and MRI 2363 Since the routine use of abdominal ultrasound became
days post diagnosis. This cat was treated with an L-CHOP commonplace at the AMC after 1984, we hypothesized
chemotherapy protocol. The third cat was euthanized for that the three decades between Mooney et al1 and this
an unknown cause but had no evidence of lymphoma on data set would result in stage migration. Stage migration
physical examination, CBC, biochemical profile, thoracic is defined as the addition of newer and more sensitive
radiographs, or abdominal ultrasound 1026 days post- staging tests, which can identify previously undetectable
diagnosis after treatment with steroids alone. The fourth lesions resulting in ‘migration’ into higher stages.6 Stage
cat had a complete necropsy performed by a board-certi- migration has been documented in humans, dogs and
fied pathologist, which revealed no evidence of recurrent cats.6,14–16 Our data showed that there were fewer stage
lymphoma on histopathology examination 666 days post- IV and stage V cases, an increased number of stage III
diagnosis. This cat received an L-CHOP chemotherapy cases and similar numbers of stage I and II according to
protocol as well as rescue protocols including radiation the AMC staging system, although no bone marrow aspi-
therapy to the brain and spinal cord, a MOPP chemother- ration cytology was performed in any cats in this study,
apy protocol and single-agent cytarabine arabinoside. which may have resulted in underestimation of stage.
One cat was lost to follow-up and censored from survival Our data suggests, but cannot confirm, the presence of
data 1 day post-diagnosis. reverse stage migration. Reverse stage migration has
been previously documented in men with prostate can-
Discussion cer after the implementation of prostate-specific antigen
This study reports an incidence of renal lymphoma of testing.17 Our hypothesis to explain the potential reverse
3.6% in a population of 740 cats diagnosed with lym- stage migration observed in our patient population is that
phoma and a 22.3% incidence in a population of 121 cats routine use of advanced diagnostics with greater sensi-
with large cell lymphoma. Others reported a similar renal tivity provides a more accurate assessment of internal
lymphoma incidence of 2.2–3.9%.11,12 However, renal organs than palpation and less sensitive imaging tech-
large cell lymphoma was reported to have an incidence niques such as radiography, which was used previously.1
of 15%, which is lower than reported here.5 The current However, since neither the current data set nor the data
Williams et al 7

sets in Mooney et al1 or Gabor et al2 had complete stag- Mooney et al1 since FeLV infection has been shown to
ing data on all cats, reverse stage migration in feline renal confer a shorter median survival time.4 The median sur-
lymphoma remains speculative. vival time of cats in Mooney et al1 is difficult to determine
Clinical staging of feline cancer patients is inherently but 17/28 cats had a complete response with a reported
imprecise because samples are not typically collected median survival of 169 days, which does not appear to
from normal-appearing tissues that might harbor lym- differ from the median survival reported in this study.
phoma. In many studies, costs associated with testing, This finding was unexpected.
risks of adverse outcomes from testing and the fact that Lymphoma of the CNS appears to be less common
complete staging is not required for successful treatment in this study than in Mooney et al.1 We speculate the
limit the number of cats undergoing an extensive staging decrease in CNS lymphoma may be related to a decrease
evaluation. It is likely that nearly all reports of clinical in FeLV infection.1 The median survival in the present
staging of feline lymphoma patients over- or underesti- study is comparable to Mooney et al1, yet only one cat
mate stage to some degree. developed CNS lymphoma during treatment compared
The authors acknowledge that this study may under- with eight cats in the previous report. The low number
estimate stage because 19/27 cats had thoracic radio- of cases with CNS involvement in this case series calls
graphs and no cats underwent bone marrow aspiration. into question the recommendation to include cytosine
In the previous study, only 8/28 cats underwent bone arabinoside in the treatment protocol for renal lymphoma
marrow aspiration, and no abdominal ultrasounds or as previously described.1 Cytosine arabinoside has been
MRIs were performed. Stage may have been over- and recommended as prophylaxis for CNS lymphoma due
underestimated in that group of cats.1 However, given to its ability to cross the blood–barrier and cats treated
that similar limitations exist in all publications reporting with a protocol containing this chemotherapy agent were
feline lymphoma stage, there may still be value in com- reported to have a lower rate of CNS lymphoma than cats
paring staging in different studies even though none of not treated with cytosine arabinoside.1 Prospective stud-
those studies are perfect. ies are indicated to determine the optimal chemotherapy
The presence of azotemia and anemia at diagnosis is protocol for renal lymphoma in cats and if CNS prophy-
considered of potential prognostic significance in renal laxis with cytosine arabinoside or any drug is indicated.
lymphoma. Based on Boyd et al,18 we hypothesized severe Another difference between this study and the prior
azotemia would result in poorer responses to chemother- one is the use of L-CHOP chemotherapy in nine cats. The
apy and shorter survival times. Previously, in cats with chemotherapy protocol used previously to treat renal
chronic kidney disease, IRIS stage at diagnosis has been lymphoma did not include doxorubicin.1 Doxorubicin
shown to predict outcome.18 Boyd et al18 also reported a was added to the chemotherapy protocol used in some
short median survival time in patients with chronic kid- cats in this study with the expectation that the addition
ney disease and anemia requiring treatment. Our study of this drug would improve survival, though statistical
did not identify azotemia or anemia as prognostic factors analysis did not confirm this outcome. Prior reports of
for survival, but anemia is one difference that might have the efficacy of doxorubicin in feline lymphoma have been
influenced survival between the cats previously reported mixed. Some studies report long survival times using
and these cats. In this study, a greater number of cats protocols without doxorubicin, some report no difference
(17/27) were anemic compared with Mooney et al,1 where in survival times between protocols with and without
14/28 cats were anemic. In at least one study of canine doxorubicin and single-agent doxorubicin chemotherapy
lymphoma, anemia was a predictor of survival.19 Dogs has not been as successful in the cat as in the dog.1,3,9,10,21–28
diagnosed with anemia and lymphoma had a median Three of the four long-term survivors (and cats poten-
hematocrit 10% lower than dogs with lymphoma with- tially ‘cured’ of renal lymphoma) were initially treated
out anemia. Both remission duration and survival were with the L-CHOP protocol, suggesting the addition of
shorter in dogs with anemia compared with dogs without doxorubicin to the treatment protocol of some cats with
anemia. This study may have been too small to identify renal lymphoma is beneficial. The infrequent occurrence
anemia as a prognostic factor for survival but the subject of renal lymphoma in this population of over 700 cats
warrants further investigation. results in a small number of cases, causing a challenge
The decrease in FeLV infections and the decrease in in detecting differences between groups. Thus, we can-
its role in lymphomagenesis has made FeLV infection not conclusively say the addition of doxorubicin is not
uncommon in cats with lymphoma.20 FeLV infection is of benefit in at least some cats with renal lymphoma.
uncommon in our patient population and thus testing Cats included within the current study treated with an
is no longer routine, as evidenced by the small number L-CHOP protocol had a treatment duration of 25 weeks,
of cats tested. Because the cats in this study likely had a unless there was evidence of progressive disease requir-
low prevalence of FeLV infection, we hypothesized the ing a change in protocol prior to that time. Cats included
survival would be longer in these cats compared with in Mooney et al1 were treated with chemotherapy for
8 Journal of Feline Medicine and Surgery 

several years. Considering the median survival time in practice’) of individual veterinary clinical patient care were
Mooney et al1 was not longer when compared with the followed. Ethical approval from a committee was therefore not
current data set, prolonged maintenance chemotherapy necessarily required.
treatment may not have clinical benefit. The efficacy of
prolonged maintenance chemotherapy has been ques- Informed consent Informed consent (either verbal or writ-
tioned in canine lymphoma.29 An interesting and unex- ten) was obtained from the owner or legal custodian of all
plainable finding regarding survival time observed in animal(s) described in this work (either experimental or non-
experimental animals) for the procedure(s) undertaken (either
both this study and Mooney et al1 is the report of a few
prospective or retrospective studies). No animals or humans
cats with very long survival times. In Mooney et al,1 at
are identifiable within this publication, and therefore addi-
least three cats survived >1 year and in the present study, tional informed consent for publication was not required.
four cats survived >1 year. The prolonged survival in the
four cats ‘cured’ of renal lymphoma in the present study
suggests prolonged maintenance chemotherapy is not ORCID iD Ashlyn G Williams https://orcid.org/0000-
0001-6100-7052
required in at least a subset of cats with renal lymphoma.
In Australian2 and Dutch cats,28 a predilection for
lymphoma in young, purebred cats, specifically Oriental References
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1473–1477.
The inclusion of two Abyssinian cats, a Siamese and a
2 Gabor LJ and Canfield PJ. Clinical and anatomical features
Burmese cat may have had an impact on survival in the of lymphosarcoma in 118 cats. Aust Vet J 1998; 76: 725–732.
prior study and explain in part why the cats in the present 3 Taylor SS, Goodfellow MR and Browne WJ. Feline extra­
study, which included no young, Oriental cats, have a nodal lymphoma: response to chemotherapy and survival
similar survival time to Mooney et al, despite there being in 110 cats. J Small Anim Pract 2009; 50: 584–592.
fewer FeLV-positive cats in this study.1 The two purebred 4 Vail DM, Moore AS and Ogilvie GK. Feline lymphoma
cats in this study were both older, 13 and 17 years of age. (145 cases): proliferation indices, cluster of differentiation
3 immunoreactivity, and their association with prognosis
in 90 cats. J Vet Intern Med 1998; 12: 349–354.
Conclusions
5 Mooney SC and Hayes AA. Lymphoma in the cat: an
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approach to diagnosis and management. Semin Vet Med
phoma in a population of 740 cats diagnosed with lym- Surg 1986; 1: 51–57.
phoma and a 22.3% incidence in 121 cats with large cell 6 Flory AB, Rassnick KM and Stokol T. Stage migration in
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unexpectedly and disappointingly short, although some 7 Veterinary Co-operative Oncology Group (VCOG). Com­
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Prospective studies are required to determine the optimal
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Acknowledgements The authors thank Drs KZ Wright and leukemia: primary intestinal origin with predominance
AM Verrilli and Ms S Vaughan-Wasser for use of their feline of a CD3/CD8 (alpha) (alpha) phenotype. Vet Pathol 2006;
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Conflict of interest The authors declared no potential pathological findings, treatment and outcome of feline
conflicts of interest with respect to the research, authorship, large granular lymphocyte lymphoma (1996–2004). Vet
and/or publication of this article. Comp Oncol 2008; 6: 102–110.
11 Chino J, Fujino Y, Kobayashia T, et al. Cytomorphological
Funding The authors received no financial support for the and immunological classification of feline lymphomas:
research, authorship, and/or publication of this article. clinicopathological features of 76 cases. J Vet Med Sci 2013;
75: 701–707.
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