FIV and Lymphoma
1. Introduction
2. Tumor Characteristics
3. FIV and Pathogenesis
4. Therapy
5. Variables to Consider
6. Prognosis
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1. Introduction
The attachment of the term "Feline AIDS" to infection with FIV has had the effect, ironically, of
deflecting many cat owners' attention away from the consequence of the infection that probably
presents the greatest threat to their cats’ lives. AIDS conjures up fears of plunging white cell
counts, cascading infections, wasting, and the like. Reports suggest, however, that the
commonest fatal consequence of FIV infection is cancer and that the commonest of the fatal
cancers is lymphosarcoma (LSA), also called lymphoma. FIV has been more loosely associated with other
cancers, such as myeloproliferative disease (MPD),squamous cell carcinioma, mast cell carcinoma, and fibrosarcoma [Magden].
But according to a recent Australian study, "The most compelling data arises from cats infected
with various local strains of FIV and living in SPF [Specific Pathogen Free] colonies around the
world. In these cats, LSA would appear to be the most common cause of death thus far
documented, rather than the expected range of diseases traditionally ascribed to longstanding FIV
infection in conventionally-reared and housed cats" [Gabor]. Lymphosarcoma is a cancer of the
immune cells called lymphocytes, which the feline immunodeficiency virus preferentially infects.
It is classified by site of occurrence: alimentary (the GI tract), mediastinal, (in cats more often
involving cranial mediastinal lymph nodes rather than the thymic region of the chest),
multicentric (in diffuse lymph nodes with possible involvement of lungs, kidneys, liver, spleen or
bone marrow), and extranodal (a miscellaneous category involving origin in sites not covered by
the other categories).
Lymphoma has been said to be the commonest tumor in cats generally, and has been identified
in all studies as being much more common in FIV+ than in FIV- cats. Cats with FIV share the
common predisposition for development of lymphoma with humans infected with HIV and
simians with SIV, with whom their tumors share a number of features [Beatty]. A retrospective
study covering sera collected in a 20 year period between 1968 and 1988 in metropolitan areas on
both U.S. coasts found an incidence of lymphosarcoma 5.6 times greater in sera positive for FIV
than in sera negative for FIV [Shelton]. (Cats co-infected with FIV and FeLV have an incidence
higher than either alone, an astounding 77.3 times greater than uninfected cats.) The study in
Australia (where the incidence of FIV in the general feline population is higher than anywhere
else that incidence statistics have been collected except Japan) found a 6- to 14-fold likelihood of
lymphosarcoma in the FIV+ versus FIV- cats studied [Gabor], the range indicating inclusion or
exclusion of cats based on varying results on FIV-status obtained with different assays. This rate,
while well below that recorded for FeLV infection, is nonetheless significant. In the Australian
study, 50% of the cats with lymphosarcoma were FIV+, a rate explained in part by the fact that
feline leukemia virus is much less prevalent in Australia than in (for instance) the U.S. [Gabor].
Younger cats with LSA tend to be FeLV+. Otherwise, most large studies show LSA as
statistically a disease of older cats. In the aforementioned Australian study, 10 years old was the
median age for diagnosis of both FIV+ and FIV- cats; the mean period post-FIV infection
diagnosis was 9 years [Gabor]. In another, the median age of cancer diagnosis was a bit lower
at 8 [Hutson]. In yet another, development of lymphoma took 2 to 6 years [Beatty]
post-infection. These findings mirror somewhat those of HIV studies, which have found that
lymphoma is generally a late manifestation of HIV infections where there is a prior history of
AIDS-defining illness and an AIDS-defining CD4+ lymphocyte count of <200 [Levine]. One
evident difference between HIV and FIV infection is that cats diagnosed with FIV had usually
not had prior AIDS-defining illnesses, a fact that can perhaps be correlated with the observation
that FIV+ cats generally are less inclined than HIV+ humans to advance inevitably to an AIDS
stage of illness. However, in the Australian study the FIV+ cats did have "significantly" lower
WBCs and neutrophil counts than did FIV- controls with lymphoma at the time of diagnosis.
On the other hand, some studies of individual or small numbers of cats deliberately infected with
FIV and observed in the laboratory found that the cats developed lymphoma in remarkably short
periods of time. One cat displayed lymphoma 9 months post-infection [Callahan-McCandlish],
prior to showing any signs of severe immune deficiency. In another instance lymphoma
developed 18 months post-infection [Poli]. It's possible that this is another instance of the difference between laboratory findings for cats parenterally infected with laboratory strains versus naturally infected cats with wild strains. However, since it has been speculated that these rapidly developed cancers stem from host
response to the initial acute viral infection [Callahan-McCandlish], it is possible that such cancers represent a subset of FIV-related lymphomas and that LSA can be a product of both acute and long term chronic infection in different circumstances.
2. Tumor Characteristics
Studies done in different regions and at different times have drawn different conclusions about
which types of LSA are more common. Although these differences may indeed reflect discrete
disease expression in various locales, some analysts have speculated that they may, in large part,
be explained by different interpretations of the classification scheme. Notes one writer, “ Many
classification schemes inadequately reflect the complexity and heterogeneity of cases. For
example, some classifications of gastrointestinal lymphoma include hepatic or splenic
involvement, whereas others consider this pattern ‘multicentric.’ It is well established that there
may be considerable overlap among anatomic sites of involvement; this is expressed as a mixed
distribution category by some authors” [Richter]. Another explanation may involve the decline
in the number of cats with feline leukemia with wide use of available vaccines. Fewer FeLV+
cats means fewer tumors of types most often found in them.
Although a 2002 study in the Netherlands found mediastinal most common [Fox], most studies
of the general cat population seem to find the alimentary type most common. One study
identified the GI tract as the most common (21%) location of tumors in FIV+ cats, as well
[Richter]. However, numerous studies have found tumor location in FIV+ cats somewhat at
variance with those of FIV-, particularly with regard to widely dispersed or less usual tumor
locations. Whereas discrete thymic or alimentary (GI) tumors predominate in retrovirus-negative cats, according to one study [Shelton], more widely dispersed development and more
unusual locations seem to characterize FIV+ cats. Possibly reflecting the previously mentioned
inconsistency in interpreting tumor type, another study found that multicentric tumors most
characterized retrovirus-infected cats[Netherlands, 2002, cited in Fox]. Yet another reported as
most common “the least common anatomic classicification of miscellaneous [extranodal?]”
[Patterson-Kane]. A third noted an "unusual distribution of tumors" [Callahan-Jones]. Yet
another, "forms more atypical (especially nasal)" than with FIV- [Gabor]. Mesenteric lymph
nodes, submandibular lymph nodes, liver, kidney, intestines, eye, periorbital area, and brain
were the sites recorded in another study [Hutson].
Studies of all cats differ with regard to the cell-type in which the tumor originates. Although
several found T cell tumors most common [Patterson-Kane][Zwahlen], more find B
cell (antibody-producing cells) most common. Large studies and small of FIV+ cats only
likewise find B cell tumors most common: 35 of 50 [Gabor], 2 of 5 with 2 non-B non-T [Endo],
7 of 8 [Callahan-Jones], and 3 of 5 [Terry].
Tumors are also divided into high, medium, and low grade, depending on the size of the
predominating cell, with high grade (infecting large cells called lymphoblasts and immunoblasts)
having the least hopeful prognosis and low grade (infecting small lymphocytes) having the most
hopeful prognosis. Low grade tumors are more common in older (>10 yrs) cats, high grade in younger (>6 yrs) [Vonderhaar]. FIV+ cats seem to have more high grade tumors reported, with studies of the
feline population generally reporting predominance of low or medium grade tumors [Beatty-Callahan].
3. FIV and Pathogenesis
Explanations for the excessive number of lymphomas suffered by FIV+ cats are the same as
those offered for HIV.
(1) A number of studies hypothesize malignant transformation of cells as a result of the high
degree of cell activation, particularly B cell activation, characteristic of the disease. In one study,
a cat experimentally infected with FIV developed lymphosarcoma in the liver and kidneys a mere
nine months after infection. The cat had no overt signs of immunodeficiency. It was therefore
suggested that "B cell activation induced shortly after FIV infection produced a large pool of
proliferating lymphocytes from which the malignant cells emerged" [Callahan-McCandlish]. The
belief, therefore, is that early events in the acute phase of infection may, at least in some
instances, lay the groundwork for a relatively rapid development of malignant lymphoma. In
cases where malignancy occurred many years after infection, either chronic or advanced-stage
immune hyperactivation would seem to be involved.
(2) Other studies have pointed in the direction of deficient or aberrant immune response as a
cause. One study monitored immunological response during the chronic phase of experimental
FIV infection in two cats which subsequently developed lymphoma. "In one cat . . . cell-mediated
immunity was depressed throughout the monitoring period but particularly from 125-200 weeks
post-infection . . . when this cat demonstrated profoundly impaired lymphocyte blastogenesis and
markedly increased interleukin-1 (IL-1) production compared to age-matched, uninfected control
cats. . . . Alterations in the levels of immunoglobulins M, A and G in CD4+-, CD8+- and
CD21+-lymphocyte sub-sets were demonstrated in both cats" [Beatty-Lawrence]. There are two
oncogenic drivers expressed in this example. One is immune deficiency. In another one-cat
study, the cat showed a marked reduction of circulating CD4+ T lymphocytes at the time of
cancer diagnosis, 18 months, post-infection. The importance of cell-mediated tumor surveillance
by cytotoxic (CD8+) T cells and by natural killer (NK) cells is well established, and both
lymphocyte subsets have shown impaired activity as a result of retroviral infection. The second
driver is immune dysregulation. The likelihood is that the skewed immune response induced by
chronic FIV infection activates oncogene pathways that facilitate malignant transformation of
cells.
(3) There has been speculation that because HIV infection has been linked to lymphoma induced
by several secondary viruses–notably Epstein-Barr virus and herpesvirus 8--perhaps common
secondary viral infections such as feline herpesvirus can play a role in tumor formation in FIV+
cats [Gabor]. Such a role has not, however, been demonstrated.
No studies to date have shown that FIV can directly cause lymphoma or any other cancer. FIV
has been isolated from in vitro cultures of feline lymphoma tumor cells [Terry], FIV proviral
genome has been detected in the genomic DNA of feline tumor cells [Endo], and it has even been
found clonally integrated into feline tumor cellular DNA [Beatty-Lawrence], meaning that it has
passed intact from one generation of cells to the next. However, the p24 FIV capsid protein (that makes up the actual viral containment wall beneath the outer envelope, whose function is attachment) has not been detected in a cell clonally integrated with FIV. If it were, this would be the "smoking gun," showing that the virus was actively replicating within the tumor cell and driving oncogene activation. Until or unless such a discovery occurs, opinion within the
research community will continue to be that FIV has only an indirect association with feline
lymphoma, not a direct, causative one.
4. Therapy
Therapy for feline lymphoma in mainstream veterinary medicine means surgery, radiation, or
chemotherapy. Surgery is usually used only in the diagnostic phase. Radiation and surgery are
sometimes used when tumors are discrete and localized in one area , and radiation is sometimes
used for palliative purposes when tumors exist in more than one location but where a particular
tumor in a particular location is believed to be responsible for symptoms significantly degrading
quality of life. “A full course of radiation involves a total of 10 to 16 treatments given 3 to 5
times a week. Adverse effects vary depending upon the region of the body treated and the
number of treatments given. Animals must anesthetized for each treatment to prevent movement
during radiation exposure” [Pet Place]. Addition of chemotherapy to radiation therapy may be
particularly indicated in cats that are FIV+ or FeLV+.
Malignant lymphomas are the most chemo-responsive cancers encountered in veterinary oncology [Helfand]. Owners, their vets, or both may be hesitant to submit an FIV+ cat to chemotherapy out of a belief
that their preexisting immunocompromised state automatically disqualifies them. Such a blanket
view is not supported by expert testimony. Oncologist Alice Villalobos has said, "I treat the FIV
positive cats the same way as the negative cats" with regard to giving or withholding
chemotherapy [Private Communication]. Dr. Leslie E Fox, writing for the 2003 Waltham Feline
Medicine Symposium says, "The FeLV antigen or FIV antibody positive cat can be treated with
the same multidrug protocols administered at the same dosages/frequency as unaffected cats.”
This is not a blanket endorsement for aggressive chemotherapy for all FIV+ cats in all
circumstances, but is an indication that a variety of factors should be weighed in making such
decisions and that a decision to go forward can be a justified, defensible option. Cats, it should
be noted, tolerate chemotherapy well--better than people, generally, and better than dogs, as well
[Ettinger]. Some side-effects are predictable in any given cat, regardless of its FIV status. These
include, "Self-limiting anorexia, vomiting, diarrhea . . . [which] may be observed in occasional
patients" [Richter]. Toxicities are most associated with cyclophosphamide, methotrexate, and doxorubicin [Vonderhaar]. (See below.) Gastronomy tubes are sometimes necessary to help a cat take in sufficient
nutrition during this phase.
Chemotherapeutic drugs are drawn from a variety of categories, based on their mode of action.
As with HIV antiviral medications, they are often used in combination because they impact
different parts of the disease process. The categories and drugs most often used within them are,
Glucocorticoid Hormones. prednisone, prednisolone, dexamethasone. Inhibit cell division and
directly destroy tumor cells.
Alkylating Agents. cyclophosphamide, chlorambucil (Leukeran). Interfere with cell division by
breaking or cross-linking DNA
Antimetabolites. cytosine arabinoside, methotrexate. Incorporate into and functionally disrupt
DNA synthesis in tumor cells.
Vinca alkaloids. Vincristine (Oncovirin). Inhibit cell division by binding to microtubules
within the cell cytoplasm.
Antitumor antibiotics. Doxorubicin (Adriamycin). Bind DNA and interfere with cell division.
Other agents. L-asparaginase (Elspar). A bacterial enzyme that kills cancer cells by depleting
their supply of L-asparagine, an amino acid. [Barlough]
Glucocorticoids, though they may improve the quality of life and are included in many (even most) combination therapeutic regimens, do not induce remissions. “The single-agent use of oral prednisone should only be instituted if pet owners, who have been educated of their therapeutic options, actively choose not to pursue superior multiagent chemotherapeutic protocols. Additionally . . . use of oral prednisone before the definitive diagnosis of lymphoma may reduce the efficacy of traditional antineoplastic agents for treating . . . lymphoma through the up-regulation of resistance mechanisms. . . . [R]esistance has been classically associated with the expression of a drug efflux pump termed P-glycoprotein (Pgp). Functionally, Pgp prevents the retention of cytotoxic agents such as doxorubicin and vincristine within lymphoma cells, allowing malignant lymphocytes to escape lethal DNA injury. Glucocorticoids have been demonstrated to up-regulate Pgp expression in malignant lymphocytes” [Fan].
Most chemotherapeutic drugs are also less than desirable as monotherapy. Vincristine has produced some long term remissions [Vonderhaar]. However, the only single chemotherapeutic agent that has offered any evidence of being able to match some combination regimens, at least in some circumstances, is doxorubicin.
One writer has called doxorubicin “a cornerstone of chemotherapy in veterinary oncology”
[Morrison, “Cancer”]. The preponderance of medical opinion, however, is that well-conceived
combinations outperform doxorubicin alone and that doxorubicin, if it is to be used, should be
used as part of a combination. L-asparaginase (Elspar) has been singled out as a worthwhile
alternative to doxorubicin [Fox], although it has also been used effectively in conjunction with doxorubicin [Zwahlen]. A number of combination protocols are possible. The most used standard protocol is referred to, acronymically, as COP, standing for Cytoxan, (cyclophosphamide), Oncovin (vincristine), and prednisone. "This protocol is relatively effective,
nontoxic and inexpensive. It is probably the treatment of choice for those practices that only occasionally use chemotherapy and without a referral practice in the area" [Cotter]. It is also convenient since most of the components are given orally [Vonderhaar].
Note: A useful resource for information on alternative therapies (holistic, homeopathic, TCM) and adjunctive therapies and links to primary sources can be found at
http://www.holistic-vet.com/cancer%20integrative.htm -- “Cancer: An Integrative Holistic
Approach”
5. Variables to Consider
A number of factors need to be taken into account--with an FIV+ cat or, for that matter, with any
cat-- in deciding whether or when to initiate chemotherapy and which agents to include. Among
these are tumor grade, tumor location, stage of disease, immunophenotype, and health at time of
diagnosis.
Tumor Grade. Low-grade tumors (those in which the cancerous cells are small) have a greater rate and length of response to therapy and are often treated with glucocorticoids and
chlorambucil only. For instance, “Low-grade and high-grade gastrointestinal lymphomas in
many ways represent different disease entities and must be considered separately,” notes one
writer. “Compared to cats with high-grade lymphoma treated with a multi-agent chemotherapy
regimen, cats with low-grade lymphoma treated with oral prednisone and chlorambucil had a
significantly better remission rate (69% versus 18%) and survival time (17 months versus 2.7
months)” [Richter]. (Actually, prednisolone is generally preferable to prednisone in cats because of greater bioavailability [Helfand].) In this regard, as in many others relating to treatment and prognosis, biopsy
is essential. As already noted, FIV+ cats develop high grade tumors at a greater rate than FIV-,
and high-grade tumors require stronger regimens.
Tumor Location. Tumors in unusual locations or associated with major organs, bone marrow, or
central nervous system, for instance, are more difficult to control with chemotherapy. As an
example, "In a 1996 study of 38 northeastern American cats, 18/38 (47%) had a complete
remission lasting less than 3 months. The responders were 6/11 (54%) cats with multicentric
lymphoma, 5/12 (41%) cats with alimentary lymphoma, and only 2/9 (22%) cats with renal
lymphoma" [Fox]. In another study of 23 cats, only anatomical location had a significant
influence on remission duration [Simon].
Stage of disease. Feline lymphoma is staged according to a five-part scheme:
Stage I Single lymph node, tumor (thymic or extranodal)
Stage II Regional lymph nodes, one side of diaphragm, Single, resectable GI nodule.
Stage III Generalized lymphadenopathy, Unresectable/multiple GI Nodule
Stage IV Liver and/or spleen involvement, Epidural involvement +/- Stage 3
Stage V Blood and/or bone marrow involvement, Multiple or infiltrative extranodal
involvement (pulmonary, CNS) +/- Stage 3 and 4.
Stages 1 and 2 are more amenable to effective treatment than stages 3, 4, and 5. Bulky
involvement of liver or spleen, or massive involvement of the abdominal area are additional
negative features.[Page]
Immunophenotype. Studies differ somewhat on the importance of T cell versus B cell origin of
tumors in relation to response to treatment. Some sources note that immunophenotype does not
appear to correlate with response to chemotherapy treatment or survival [Richter, Patterson-Kane]. Others state that “immunophenotype of lymphoma may have considerable prognostic
significance. . . . For example, because T-cell lymphomas have a poorer prognosis, an aggressive
protocol should be used” [Morrison, “Lymphoma”].
Health at Time of Diagnosis. One writer notes,"The sick cat with lymphoma is perhaps the biggest challenge to achieving a good response to therapy. Cats that are sick at the time of
diagnosis are more likely to experience adverse events associated with anticancer drugs and do
not survive as long as cats who are otherwise 'healthy'" [Fox]. A poignant example [in a private
communication] is provided by Lucky, a geriatric (13 year old) FIV+ cat, burdened with diabetes
and kidney disease at the time of his diagnosis with alimentary lymphosarcoma (a sizable
duodenal tumor). Writes Lucky's owner, "At our first oncology appt. the vet said he would like
to perform some tests and insert a feeding tube as Lucky had completely gone off food. He said
not eating was because of the duodenum mass. We mushed his food up and gave him about 40ml
every 4-6 hours. He did some biopsies etc of the next couple of days and when the results came
back he started on Chemotherapy straight away. From the ultrasound to the first chemo was
approx 10 days. We were led to believe that Lucky would survive this and have a few more years
left. . . . We were also told by the oncologist that nearly all cats have some kind of strain of FIV
and that it doesn't cause problems . . . . About 24 hours later Lucky began vomiting terribly and
became very weak and floppy. He had been though hell and obviously would go through a lot
more without any success so we made the difficult decision and had him put to sleep. If I could
turn back the clock I would have never taken him to the oncologist." It's not clear, though
possible, that Lucky's kidney disease and diabetes owed anything to his FIV+ status; nor is it
clear that Lucky was in a highly immunosuppressed state as a result of his FIV at the time
chemotherapy was begun. But it shows a high degree of optimism on the part of the oncologist,
the owners, or both to foresee "years" of life ahead for a cat with a massive tumor and both
chronic and immediate impairment of health at the time therapy was to begin. That an oncologist
should so misunderstand the frequency of FIV in the cat population is shocking; that he should
regard FIV as an entirely negligible risk factor is surprising.
Even in the absence of significant clinical signs of poor health, chemotherapy is
immunosuppressive by its very nature. Anemia and neutropenia are predictable side effects.
Cats who, at the time chemotherapy is being weighed, have laboratory evidence of significant
immunosuppression, anemia, or organ impairment face significantly more challenging odds of
success. One source cites a PCV/HCT of <25% prior to initiation of therapy as a negative prognostic indicator for some types (nasal, alimentary) of lymphoma [Helfand]. Neutrophil counts are particularly significant since a low ANC (absolute neutrophil count) leaves an animal highly vulnerable to infection. "Neutrophil counts should be greater than
2000/μl prior to the administration of [chemotherapeutic] drugs. If the neutrophil count is less
than 2000/μl . . . it is best not to treat at this time" [Ward]. In this regard, human medicine is at
a distinct advantage by comparison to feline medicine. Drugs such as Neupogen (Granulocyte
Colony Stimulating Factor, or G-CSF) can support chemotherapy by stimulating neutrophil
production; drugs such as Epogen or Procrit (erythropoietin) can stimulate red cell production.
Although these human drugs are clinically available to feline medicine, their human origin often
makes their use impractical. Within about two weeks, cats mount an antibody response to
G-CSF that negates its action for most purposes. However, cats receiving chemotherapy may have their immune response suppressed to the point where antibody response is retarded. Human erythropoeitin can cause rejection responses and
potentially life-threatening refractory anemia within weeks or within months, although many cats
can use it for extended periods of time. G-CSF and erythropoietin of feline origin do exist for
research purposes, but are clinically unavailable.
It should also be pointed out that HAART (highly active antiretroviral therapy), popularly known
as the "triple cocktail" of HIV-specific drugs, can make possible modified treatment protocols for
humans infected with HIV whose clinical and laboratory parameters at diagnosis make
chemotherapy an unacceptably poor option. Low-dose chemotherapy has a heartening record of
response for such people [Levine] because of immune reconstitution made possible by reduction
of virus to low or undetectable levels. With a few exceptions, cats with FIV do not receive HAART. Zidovudine (AZT)
is the only human antiretroviral drug recognized as clinically available for feline use, and it
cannot achieve a level of viral suppression comparable to HAART. In fact, AZT is a difficult
drug even for humans undergoing chemotherapy because of its deleterious effect on red cell
production. Cats have an even more difficult time with it, and inevitably become anemic in a
matter of weeks.
6. Prognosis
There has never been a published study of survival rates for FIV+ cats by comparison to FIV-
controls. A 1991 study of 1160 cats found twenty-nine (2.5%) cats who were FIV positive.
Eighteen of the twenty-nine (62%) had some form of cancer: myeloproliferative disease (5/18),
lymphoma (5/18), and squamous cell carcinoma (7/18). The FIV-infected cats with lymphoma
ranged from 4 to 14 years old and survived 60 days if untreated. Cats that underwent
chemotherapy survived 39, 45, 217, and 243 days. It is difficult to draw conclusions from such a
small sampling. In addition, five of the twenty-nine cats with cancer were also FeLV+, but it is
not clear how many, if any, belong to the group with lymphoma. The good new is that these cats
were older on average than those with myeloproliferative disease, whose survival durations with
treatment, though varied, were less than those of the cats with lymphoma [Hutson].
All studies involving treated cats with feline leukemia and LSA invariably report shorter
durations of survival both with and without treatment. In one study, for instance, they were as
likely to have a complete response to therapy as FeLV- cats; however, they did not live as long
because of complications related to infection and cytopenias [Fox]. One writer places the
average duration of survival in cats aggressively treated for lymphoma at nine months, for
FeLV+ cats at 4.2 months [Ward]. It is unclear to what extent FIV+ cats can be compared to
FeLV+. Both diseases are immunosuppressive, but cats with FeLV develop cancers much earlier
on average, and it is hard to say how comparable the processes leading to tumorogenesis are. A
guess would be that on average FIV+ cats fall somewhere in the range between FeLV+ and
FIV-/FeLV- cats. All prognostic factors that follow are for cats generally, not for FIV+ cat. It is
a reasonable assumption, however, that factors favoring cats generally will also favor FIV+ cats.
Tumor Grade, Stage of Disease, and Health at the Time Therapy is Initiated, as already noted,
are major prognostic factors. Cats with low-grade LSA have a much more favorable prognosis
than those with high-grade. A study of cats with both high and low-grade gastrointestinal
lymphoma found a rate of complete remission with treatment of 69% in the cats with low grade
versus 18% in cats with high grade, and a survival time of 17 months versus 2.7 months
[Richter]. In another study of all lymphomas, 56% of cats achieved a complete response to
treatment and 39% achieved a partial response; only 5% had no response. No association was
found between any other risk factors and response to treatment. Duration of median remission
was 428 days for cats with a partial response, compared with 897 days for cats with a complete
response. Overall median survival time was 704 days [Kiselow]. So survival times with
treatment in excess of one year are extremely likely, and those in excess of two years are not
unrealistic. Stage is also an issue. "Cats with bulky stage III or IV disease may fail to achieve a
complete remission more often (50%) than cats without extensive tumor burdens (90%)" [Page].
Health at the time of treatment is singled out by most sources. Since FIV+ cats are less likely to
have exhaustive examinations on a regular basis in light of their FIV+ status than are humans in
light of an HIV+ status, it is logical to assume that compromised health is likely to be a primary
reason for seeking out the treatment that results in the diagnosis of cancer.
Leukocytosis, especially elevated lymphocytes and circulating abnormal lymphoid cells suggest bone marrow involvement. When tumor cells have spread to the bone marrow, prognosis for complete remission is poorer [Vonderhaar].
Initial Response to Therapy is another very important prognostic factor--and one of
considerable practical importance. Some call it the most reliable prognostic factor. Cats that
achieve a complete remission initially may continue to have durable remissions, extending for
more than 12-18 months vs 6-8 Months for those that do not [Page]. "Generally, cats that have
not responded favorably to the first 4–6 weeks of therapy continue to have a poor response to
therapy despite the addition of other drugs. Likewise, cats that experience frequent adverse drug
events requiring treatment delays and dose reductions often continue to have difficulty tolerating
other anticancer drugs. Repeated dose reductions resulting in subtherapeutic treatment dosages
will shorten disease free interval and decrease lifespan" [Fox]. What this means is that an owner
and/or vet doubtful about a decision to commit a cat to chemotherapy may be encouraged to
proceed, knowing that within 4 to 6 weeks, it should become clear whether the cat is responding
optimally, guardedly, or not at all. This information can then provide a basis for deciding
whether continued treatment is justified.
Cats with a long first remission have a better chance for a second remission than do those that
relapse early [Zwahlen]. Those that relapse off treatment can sometimes be re-induced into remission with
the same drugs used to achieve the first remission [Cotter]. Studies of COP combination therapy
have produced differing statistics on the number of cats that achieve complete remission: 18/38
(47%), 30/38 (79%), 46/61 (75%) [Fox]. A complete remission offers a significantly improved
duration of survival over a partial remission (defined as greater than a 50% reduction in tumor
size). Cats treated with a combination protocol that includes either doxorubicin or l-asparaginase
survive 12-18 months if first remission is complete. If it is only partial, survival time drops
preciptitously to 6-8 months [Fox]. A recent (2008) study of 23 cats so treated produced a
complete remission in 17/23 (74%); 14% attained partial remission. Median survival in cats with
Complete remission was 296 days (range, 50–2,520 days). 6-months/82%, 1 year/47%, 2
years/34%, and 3–5-years/27%. Survival of cats with partial remission ranged from 38 to 120
days [Simon].
Relapse can occur at any time, and the chance for a second remission is less than for the first, and
if achieved, is usually shorter. "Second remissions are difficult to achieve and short-lived in cats.
Information about effective protocols is scarce. If COP was used successfully to induce a first
remission, then the addition of doxorubicin and/or lasparaginase may help reinduce remission. If
a doxorubicin/l-asparaginase protocol was used initially and complete remission was achieved,
then the first 4 weeks of that effective protocol can be given again" [Fox]. In one study, a salvage
protocol designated MOPP produced an additional median remission duration of 3 weeks and
median survival about 2 months after initiation of the protocol.
Knowing when to say “enough” is the saddest and most difficult part of cancer therapy. Writes
one person who recollects pushing too hard for too long, “Clyde . . . did awful on chemo, and my vet and
I made a mistake to keep pushing him. He quit eating; at that time I wasn't good at assist-feeding,
then we decided to place him an e-tube. . . . [A]fter the surgery he never stopped vomiting, not
even when we removed the tube. We gave up on chemo . . . .I was so blind and arrogant
thinking I could cure him (I had - still have - another cat, Matilda FIV-, who was in remission
from a multicentric lymphoma) and never questioned my vet if we were pushing too much.
Nowadays, I still am a chemo believer, but I learned to give up when the cat is not doing well,
and when the resources to make him/her feel better fail.”
_______________________________________________________________________________
References
Barlough, JE. “Cancer.” The Cornell Book of Cats. 1997.
Beatty JA, Callanan JJ, Terry A, Jarrett O, Neil JC. Molecular and immunophenotypical
characterization of a feline immunodeficiency virus (FIV)-associated lymphoma: a direct role for
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