Introduction

Lymphoma is the most common neoplasia seen in cats and it is believed to encompass a third of all feline tumors.¹ It affects cats of any age ranging from 4 months to 9 years, but typically it is seen in two peaks occurring between 1–2 years² and 7–8 years of age^3,4. Domestic short haired cats are the most common breed affected,^4,5 but Siamese and oriental mixes have been seen to have a higher risk for developing the disease^3,4,6. Male cats also seem to be the predominant gender affected in most studies.^4,6,7 The occurrence of the feline lymphoma has also been associated with feline leukemia virus infection (FeLV). It is estimated that approximately 25% of FeLV positive cats develop lymphoma within their lifetime.⁴ Until the 1990s, 70% of cats with malignant lymphoma were FeLV positive, but due to increased vaccination the prevalence of FeLV cats has declined and may have changed the predominant presentation and signalment of cats with lymphoma.⁵ Although development of lymphoma is higher in FeLV infection, feline immunodeficiency virus (FIV) has also been shown to cause lymphoma in some cats.⁴ Yet cats with FIV have a 5 times higher rate of developing lymphoma than non-infected cats. At this time, the exact mechanism for FIV to cause lymphoma has yet to be determined.^4,8

Feline lymphoma is a heterogeneous disease entity that results in a variety of clinical signs and difficulty in classification.⁴ In an effort to examine prognosis based on clinical examination, two main classifications of lymphoma were devised, these are the anatomic form³ and clinical staging⁹. The main anatomic forms are alimentary, mediastinal, multicentric, and extranodal (unclassified). Clinical staging of lymphoma is another form of classification that has been associated with prognosis in some studies,¹ but not in others^5,10. The most commonly used feline lymphoma staging is found in Current Veterinary Therapy (CVT) X which was adapted from Mooney.¹ Stages range from I, a single tumor or anatomic area, to Stage V, with involvement of CNS, bone marrow, or both. Stages II and I appear to be prognostically significant and cats in these stages have a longer survival time.^1,6,11

Several chemotherapy protocols have been describe and include cyclophosphamide, vincristine, and prednisone (COP),^5,10 COP with the addition of l-asparaginase and methotrexate,^1,4,11 doxorubicin as a single agent,^4,12,13 and chlorambucil and prednisone^10,14. Multiple drug protocols using combinations of vincristine, l-asparaginase, cyclophosphamide, doxorubicin, methotrexate, and prednisone have also been described^15-17 although methotrexate is no longer used.

The multiple drug protocol used at the University of Florida is the Madison-Wisconsin (MW) protocol first reported by Vail and MacEwen.¹⁸ The University of Florida experience with the MW protocol was published in a JAVMA article by Milner et al.¹⁹ The study was a retrospective study of 38 cats with lymphoma. The study reported on age, sex, breed, FeLV and FIV infection status, anatomic form, clinical stage, and survival time. Immunophenotyping was not performed. The median ± SD age of the cats were 10.9 ± 4.4 years with an overall median survival time (MST) of 210 days. The duration of first remission was 156 days. Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first remission or survival time. Of the 38 cats 18 (47%) cats had complete remission, 14 (37%) had partial remission, and 6 (16%) had no response. The duration of first remission was significantly longer for cats with complete remission (654 days) than for cats with partial remission (114 days). The MST with complete remission (654 days) was significantly longer than median survival time for cats with partial remission (122 days) and for cats with no response (11 days).

Overall the initial response to treatment was the most significant predictor of survival time. The 38 cats formed part of a larger cohort [n=163] (not reported in the study) of cats seen at the University of Florida. Remarkably, out of the 163 cases of lymphoma, 45% of the cats were not treated. At the time of diagnosis 60% of the cats were euthanized although the majority (26%) were in Stage I which sadly may have had a better prognosis.^1,6,11 Nevertheless, the early euthanasia rate is most likely due to cats presenting with the appearance of clinical signs (i.e., substage b).⁷ Unlike dogs, most cats show overt clinical signs and appear ill at presentation.^7,4,11 When treated with only supportive care the average survival less than 2 weeks and an average of 5 days. This group had the lowest survival time in the study with only 10% surviving to 36 days. In contrast to the MW-protocol treated cats, the cats treated with only prednisone had a median survival of 50 days. A large proportion of these cats were on palliative care which no doubt contributed to the shorter survival.

In conclusion little has changed since the 1998 report by Vail et al.⁶ who concluded that "When all prognostic factors were accounted for by multivariate analysis, response to therapy, FeLV status, and clinical substage were predictive of outcome. FeLV-negative cats that achieved a complete response following induction therapy were likely to have durable (i.e., >6-month) responses, particularly when doxorubicin was included in the chemotherapy protocol. However, FeLV-positive cats had significantly shorter remission and survival times with available chemotherapeutic protocols."

References

1.  Mooney SC, Hayes AA, MacEwen EG, Matus RE, Geary A, Shurgot BA. Treatment and prognostic factors in lymphoma in cats: 103 cases (1977–1981). J Am Vet Med Assoc. 1989;194(5):696–702.

2.  Guillermo CC. What is new on feline lymphoma? J Feline Med Surg. 2001;3(4):171–176.

3.  Gabor LJ, Malik R, Canfield PJ. Clinical and anatomical features of lymphosarcoma in 118 cats. Aust Vet J. 1998;76(11):725–732.

4.  Moore AS, Ogilvie GK. Lymphoma. In: Ogilvie GK, Moore AS, eds. Feline Oncology: A Comprehensive Guide to Compassionate Care. Trenton, NJ: Veterinary Learning Systems; 2001:191–219.

5.  Teske E, van Straten G, van Noort R, Rutteman GR. Chemotherapy with cyclophosphamide, vincristine, and prednisolone (COP) in cats with malignant lymphoma: new results with an old protocol. J Vet Intern Med. 2002;16(2):179–186.

6.  Vail DM, Moore AS, Ogilvie GK, Volk LM. Feline lymphoma (145 cases): proliferation indices, cluster of differentiation 3 immunoreactivity, and their association with prognosis in 90 cats. J Vet Intern Med. 1998;12(5):349–354.

7.  Cotter SM. Treatment of lymphoma and leukemia and cyclophosphamide, vincristine, and prednisone: II. Treatment of cats. J Am Anim Hosp Assoc. 1983;19:166–172.

8.  Gabor LJ, Love DN, Malik R, Canfield PJ. Feline immunodeficiency virus status of Australian cats with lymphosarcoma. Aust Vet J. 2001;79(8):540–545.

9.  Mooney SC, Hayes AA. Lymphoma in the cat: an approach to diagnosis and management. Semin Vet Med Surg (Small Anim). 1986;1(1):51–57.

10. Mahony OM, Moore AS, Cotter SM, Engler SJ, Brown D, Penninck DG. Alimentary lymphoma in cats: 28 cases (1988–1993). J Am Vet Med Assoc. 1995;207(12):1593–1598.

11. Jeglum KA, Whereat A, Young K. Chemotherapy of lymphoma in 75 cats. J Am Vet Med Assoc. 1987;190(2):174–178.

12. Peaston AE, Maddison JE. Efficacy of doxorubicin as an induction agent for cats with lymphosarcoma. Aust Vet J. 1999;77(7):442–444.

13. Kristal O, Lana SE, Ogilvie GK, Rand WM, Cotter SM, Moore AS. Single agent chemotherapy with doxorubicin for feline lymphoma: a retrospective study of 19 cases (1994–1997). J Vet Intern Med. 2001;15(2):125–130.

14. Fondacaro JV, Richter KP, Carpenter JL. Feline gastrointestinal lymphoma: 67 cases (1988–1996). European Journal of Comparative Gastroenterology. 1999;4:5–11.

15. Matus RE. Chemotherapy of lymphoma and leukemia. In: Kirk RW, ed. Current Veterinary Therapy X. Philadelphia, PA: W.B. Saunders; 1989:482–488.

16. 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(8):1144–1149.

17. Malik R, Gabor LJ, Foster SF, McCorkell BE, Canfield PJ. Therapy for Australian cats with lymphosarcoma. Aust Vet J. 2001;79(12):808–817.

18. Vail DM, MacEwen EG. Feline lymphoma and leukemias. In: Withrow SJ, MacEwen EG, eds. Small Animal Clinical Oncology. 3rd ed. Philadelphia, PA: W.B. Saunders Company; 2001:590–611.

19. Milner RJ, Peyton J, Cooke K, et al. Response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol: 38 cases (1996–2003). J Am Vet Med Assoc. 2005;227(7):1118–1122.