Das multizentrische Lymphom bei 411 Hunden – eine epidemiologische Studie

Zusammenfassung

Ziel: Überblick über die epidemiologische Situation des multizentrischen Lymphoms (ML) des Hundes in Deutschland. Material und Methoden: 411 Hunde mit ML wurden retrospektiv hinsichtlich Rasse,Körpergewicht und des Anteils der Hunde mit Hyperkalzämie bzw. T- und B-Zell-Lymphom ausgewertet und statistisch mit zwei Vergleichspopulationen verglichen (Klinikpopulation Tierklinik Hofheim, n = 52142; krankenversicherte Hunde, n = 123423). Ergebnisse: 298 (72, 5%) der 411 Hunde gehörten 86 verschiedenen Rassen an, 113 (27, 5%) waren Mischlinge. Bei Gegenüberstellung mit beiden Vergleichspopulationen zeigte sich übereinstimmend eine Rasseprädisposition für American Pitbull Terrier (Quotenverhältnis [QV] 5, 2 bzw. 18, 5), American Staffordshire Terrier (QV 3, 3 bzw. 4, 6), Briard (QV 5, 6 bzw. 9, Bullmastiff (QV 7, 8 bzw. 5, 0), Irish Setter (QV 3, 1) und Rottweiler (QV 2, 8 bzw. 3, 6). Golden Retriever (n = 22, QV 1, 3 bzw. 0, 9) und Berner Sennenhunde (n = 22, QV 2, 4 bzw. 2, 0) waren in absoluten Zahlen häufig vertreten, doch ergab sich beim Vergleich mit den Vergleichspopulationen lediglich ein QV < 3. Das durchschnittliche Körpergewicht betrug 30, 2 ± 13, 7 kg, nur 75 (18%) Hunde wogen weniger als 15 kg. Bei den kleineren Hunden (< 15 kg KM) waren West Highland White Terrier (n = 12) gehäuft vertreten. Das mittlere Alter der Hunde lag bei 7, 9 ± 2, 7 Jahren. Hunde ≥ 15 kg waren signifikant (p < 0, 001) jünger (7, 6 ± 2, 4 Jahre) als Hunde < 15 kg (9, 3 ± 3, 2 Jahre). Hunde mit B-Zell-Lymphom hatten ein signifikant (p < 0, 001) höheres Alter (8, 5 ± 2, 6 Jahre) als Hunde mit T-Zell-Lymphom (6, 4 ± 1, 8 Jahre). Eine Geschlechtsprädisposition ließ sich nicht nachweisen (54% männlich, 46% weiblich). Eine paraneoplastische Hyperkalzämie als Zeichen eines T-Zell-Lymphoms lag bei 44 (11, 4%) Hunden vor. 20, 6% bzw. 79, 4% der Hunde wiesen einen T- bzw. B-Zell-Immunphänotyp auf. Klinische Relevanz: Bereits bekannte Rasseprädispositionen konnten bestätigt und bislang unbekannte Rassehäufungen identifiziert werden (Briard, Irish Setter). Bei kleineren Hunden (< 15 kg) tritt das ML in deutlich höherem Alter auf.

Summary

Objective: To provide an overview of the epidemiology of canine multicentric lymphoma in Germany. Material and methods: A total of 411 dogs with multicentric malignant lymphoma were retrospectively analysed regarding breed, age, sex, weight and the number of animals dogs with hypercalcaemic lymphoma and B-/T-immunophenotype, and compared to two reference populations (total own clinic population, n = 52 142; dogs with health insurance in Germany, n = 123 423). Results: In total, 298 (72.5%) of the 411 dogs belonged to 86 different breeds, while 113 (27.5%) dogs were mixed breed. In comparison to both reference populations, a breed predisposition for the American Pitbull Terrier (odds ratio [OR] 5.2 and 18.5), American Staffordshire Terrier (OR 3.3 and 4.6), Briard (OR 5.6 and 9.5), Bullmastiff (OR 7.8 and 5.0), Irish Setter (OR 3.3 and 4.1) and Rottweiler (OR 2.8 and 3.6) was found. Golden Retrievers (n = 22, OR 1.3 and 0.9) and Bernese Mountain Dogs (n = 22, OR 2.4 and 2.0) were frequently affected in absolute numbers, but when compared to the reference populations an OR < 3 was detected. Mean body weight was 30.2 ± 13.7 kg; only 75 (18%) dogs weighed < 15 kg. Amongst the small dogs (< 15 kg), there was a large number of West Highland White Terriers (n = 12). Mean age of the dogs with lymphoma was 7.9 ± 2.7 years. Dogs weighing ≥ 15 kg were significantly (p < 0.001) younger (7.6 ± 2.4 years) compared to dogs weighing < 15 kg (9.3 ± 3.2 years). Dogs with a B-cell immunophenotype (8.5 ± 2.6 years) were significantly older compared to dogs with a T-cell immunophenotype (6.4 ± 1.8 years) (p < 0.001). There was no gender predisposition (54% male, 46% female). Hypercalcaemia as an indicator of T-cell lymphoma was present in 44 (11.4%) of the dogs. A T-cell and B-cell immunophenotype was found in 20.6% and 79.4% of the dogs, respectively. Clinical relevance: This study confirms previous data about breed predispositions for canine malignant multicentric lymphoma and demonstrates that further breeds are predisposed (Briard, West Highland White Terrier, Irish Setter). Small-breed dogs (< 15 kg BM) appear to be affected with lymphoma at a greater age.

Schlüsselwörter

Alter - Geschlecht - West Highland White Terrier - Hyperkalzämie - T-Zell-Lymphom - Rasseprädisposition - Referenzpopulation

Keywords

Breed predisposition - hypercalcaemia - T-cell lymphoma - reference population

• Literatur

• 1 Bäckgren AW. Lymphatic leukosis in dogs - an epizootological clinical and haematological study. Acta Vet Scand 1965; 6 (Suppl. 01) 1-80.
• 2 Brodsky EM, Maudlin GN, Lachowicz JL, Post GS. Asparaginase and MOPP treatment of dogs with lymphoma. J Vet Intern Med 2009; 23 (03) 578-584.
• 3 Chiu BC, Hou N. Epidemiology and etiology of non-hodgkin lymphoma. Cancer Treat Res 2015; 165: 1-25.
• 4 Cohen D, Booth S, Sussman O. Canine Lymphoma. WHO Conference on comparative studies in leukemias.. Philadelphia, Penna; Geneva, Switzerland: 1961
• 5 Daters AT, Mauldin GE, Mauldin GN, Brodsky EM, Post GS. Evaluation of a multidrug chemotherapy protocol with mitoxantrone based maintenance (CHOP-MA) for the treatment of canine lymphoma. Vet Comp Oncol 2009; 8 (01) 11-22.
• 6 Dobson JM, Blackwood LB, McInnes EF, Bostock DE, Nicholls P, Hoather TM, Tom BD. Prognostic variables in canine multicentric lymphoma. J Small Anim Pract 2001; 42 (08) 377-384.
• 7 Dorn CR, Taylor DO, Hibbard HH. Epizootiologic characteristics of canine and feline leukemia and lymphoma. Am J Vet Res 1967; 28 [phone].
• 8 Edwards DS, Henley WE, Harding EF, Dobson JM, Wood JL. Breed incidence of lymphoma in a UK population of insured dogs. Vet Comp Oncol 2003; 1 (04) 200-206.
• 9 Egenvall A, Nodtvedt A, Penell J, Gunnarsson L, Bonnett BN. Insurance data for research in companion animals: benefits and limitations. Acta Vet Scand 2009; 51: 42.
• 10 Fournel-Fleury C, Ponce F, Felman P, Blavier A, Bonnefont C, Chabanne L, Marchal T, Cadore JL, Goy-Thollot I, Ledieu D, Ghernati I, Magnol JP. Canine T-cell lymphomas: a morphological, immunological, and clinical study of 46 new cases. Vet Pathol 2002; 39 (01) 92-109.
• 11 Garrett LD, Thamm DH, Chun R, Dudley R, Vail DM. Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma. J Vet Intern Med 2002; 16 (06) 704-709.
• 12 Glickman LT, Raghavan M, Knapp DW, Bonney PL, Dawson MH. Herbicide exposure and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers. J Am Vet Med Assoc 2004; 224 (08) 1290-1297.
• 13 Glickman LT, Schofer FS, McKee IJ, Reif JS, Goldschmidt MH. Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. J Toxicol Environ Health 1989; 28 (04) 407-414.
• 14 Greenlee PG, Filippa DA, Quimby FW, Patniak AK, Calvano SE, Matus RE, Kimmel M, Hurvitz AI, Liebermann PH. Lymphomas in dogs. A morphologic, immunologic, and clinical study. Cancer 1990; 66 (03) 480-490.
• 15 Grulich AE, Vajdic CM. The epidemiology of non-Hodgkin lymphoma. Pathology 2005; 37 (06) 409-419.
• 16 Jagielski D, Lechowski R, Hoffmann-Jagielska M, Winiarczyk S. A retrospective study of the incidence and prognostic factors of multicentric lymphoma in dogs (1998-2000). J Vet Med A Physiol Pathol Clin Med 2002; 49 (08) 419-424.
• 17 Keller ET, MacEwen EG, Rosenthal RC, Helfand SC, Fox LE. Evaluation of prognostic factors and sequential combination chemotherapy with doxorubicin for canine lymphoma. J Vet Intern Med 1993; 7 (05) 289-295.
• 18 Kessler M, Kandel B. Chemotherapie des malignen Lymphoms beim Hund: Ergebnisseund Erfahrungen mit dem „Hofheimer Protokoll“ bei 57 Patienten. Kleintierprax 2003; 48: 261-328.
• 19 Lurie DM, Lucroy MD, Griffey SM, Simonson E, Madewell BR. T-cell-derived malignant lymphoma in the boxer breed. Vet Comp Oncol 2004; 2 (03) 171-175.
• 20 Marconato L, Leo C, Girelli R, Salvi S, Abramo F, Bettini G, Comazzi S, Nardi P, Albanese F, Zini E. Association between waste management and cancer in companion animals. J Vet Intern Med 2009; 23 (03) 564-569.
• 21 Messinger JS, Windham WR, Ward CR. Ionized hypercalcemia in dogs: a retrospective study of 109 cases (1998-2003). J Vet Intern Med 2009; 23 (03) 514-519.
• 22 Modiano JF, Breen M, Burnett RC, Parker HG, Inusah S, Thomas R, Avery PR, Lindblad-Toh K, Ostrander EA, Cutter GC, Avery AC. Distinct B-Cell and T-Cell lymphoproliferative disease prevalence among dog breeds indicates heritable risk. Cancer Res 2005; 65 (13) 5654-5661.
• 23 Onions DE. A prospective survey of familial canine lymphosarcoma. J Natl Cancer Inst 1984; 72 (04) 909-912.
• 24 Pastor M, Chalvet-Monfray K, Marchal T, Keck G, Magnol JP, Fournel-Fleury C, Ponce F. Genetic and environmental risk indicators in canine non-Hodgkin’s lymphomas: breed associations and geographic distribution of 608 case diagnosed throughout France over 1 year. J Vet Intern Med 2009; 23 (02) 301-310.
• 25 Ponce F, Marchal T, Magnol JP, Turinelli V, Ledieu D, Bonnefont C, Pastor M, Delignette ML, Fournel-Fleury C. A morphological study of 608 cases of canine malignant lymphoma in France with a focus on comparative similarities between canine and human lymphoma morphology. Vet Pathol 2010; 47 (03) 414-433.
• 26 Priester WA. Canine lymphoma: relative risk in the boxer breed. J Natl Cancer Inst 1967; 39 (05) 833-845.
• 27 Priester WA, McKay FW. The occurrence of tumors in domestic animals. J Natl Cancer Inst 1980; Monograph 54 (166) 1-210.
• 28 Roman E, Smith AG. Epidemiology of lymphomas. Histopathology 2011; 58 (01) 4-14.
• 29 Ruslander DA, Gebhard DH, Tompkins MB, Grindem CB, Page RL. Immunophenotypic characterization of canine lymphoproliferative disorders. In Vivo 1997; 11 (02) 169-172.
• 30 Skrabek P, Turner D, Seftel M. Epidemiology of non-Hodgkin lymphoma. Transfus Apher Sci 2013; 49 (02) 133-138.
• 31 Smith AN. The role of neutering in cancer development. Vet Clin North Am Small Anim Pract 2014; 44 (05) 965-975.
• 32 Summers JF, Diesel G, Asher L, McGreevy PD, Collins LM. Inherited defects in pedigree dogs. Part 2: Disorders that are not related to breed standards. Vet J 2010; 183 (01) 39-45.
• 33 Teske E. Canine malignant lymphoma: a review and comparison with human non-Hodgkin’s lymphoma. Vet Q 1994; 16 (04) 209-219.
• 34 Teske E, de Vos JP, Egberink HF, Vos JH. Clustering in canine malignant lymphoma. Vet Q 1994; 16 (02) 134-136.
• 35 Thomas R, Seiser EL, Motsinger-Reif A, Borst L, Valli VE, Kelley K, Suter SE, Argyle D, Burgess K, Bell J, Lindblad-Toh K, Modiano JF, Breen M. Refining tumor-associated aneuploidy through ’genomic recoding’ of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas. Leuk Lymphoma 2011; 52 (07) 1321-35.
• 36 Valli VE, Kass PH, San Myint M, Scott F. Canine lymphomas: association of classification type, disease stage, tumor subtype, mitotic rate, and treatment with survival. Vet Pathol 2013; 50 (05) 738-748.
• 37 Valli VE, Vernau W, de Lorimier LP, Graham PS, Moore PF. Canine indolent nodular lymphoma. Vet Pathol 2006; 43 (03) 241-256.
• 38 Van Pelt RW, Conner GH. Clinicopathologic survey of malignant lymphoma in the dog. J Am Vet Med Assoc 1968; 152 (07) 976-984.
• 39 von Euler H, Einarsson E, Olsson U, Lagerstedt AS, Eriksson S. Serum thymidine kinase activity in dogs with malignant lymphoma: a potent marker for prognosis and monitoring the disease. J Vet Intern Med 2004; 18 (05) 696-702.
• 40 Zemann BI, Moore AS, Rand WM, Mason G, Ruslander DM, Frimberger AE, Wood CA, L’Heureux DA, Gliatto J, Cotter SM. A combination chemotherapy protocol (VELCAP-L) for dogs with lymphoma. J Vet Intern Med 1998; 12 (06) 465-470.