Retrospective evaluation of clinical outcome after chemotherapy for lymphoma in 15 equids (1991‐2017)

Luethy, Daniela; Frimberger, Angela E.; Bedenice, Daniela; Byrne, Barbara S.; Groover, Erin S.; Gardner, Rachel; Lewis, Trisha; MacDonald, Valerie; Proctor‐Brown, Lauren; Tomlinson, Joy E.; Rassnick, Kenneth M.; Johnson, Amy L.

doi:10.1111/jvim.15411

Cited by 25 publications

(23 citation statements)

References 25 publications

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“…However, in another study, dogs diagnosed with B‐cell lymphoma did have higher TK1 activity than those with T‐cell lymphoma 10 . The most common immunophenotype identified in horses is T‐cell rich large B‐cell lymphoma, as demonstrated in previous reports of equine lymphoma 2,17,18 . Given this variation between immunophenotypes in canines, it could be that this specific immunophenotype in horses does not reliably cause elevations in serum TK1 activity.…”

Section: Discussionmentioning

confidence: 79%

Clinical performance of a commercially available thymidine kinase 1 assay for diagnosis of lymphoma in 42 hospitalized horses (2017‐2020)

Moore

Stefanovski

Luethy

2021

Veterinary Internal Medicne

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Background Antemortem definitive diagnosis of lymphoma in horses is often difficult. Thymidine kinase 1 (TK1) assay is a potentially useful biomarker for lymphoma in horses. Hypothesis/objectives To report the clinical performance of a commercially available TK1 assay for diagnosis of lymphoma in horses. We hypothesized that there would be no association between serum TK1 activity and a diagnosis of lymphoma in horses. Animals Forty‐two hospitalized horses, 14 with a definitive diagnosis of lymphoma, 4 with other neoplasia, and 24 with inflammatory disease. Methods Retrospective medical record review, groups were compared via Kruskal‐Wallis and Mann‐Whitney tests, and logistic regression was performed. Results Median (range) TK1 was 3 U/L (0.4‐17.7 U/L) in horses with lymphoma and 3.9 U/L (0.8‐94 U/L) in horses without lymphoma (P = .59). There was no significant difference in total protein between horses with and without lymphoma (6.6 g/dL [5.5‐8.3 g/dL] vs 6.6 g/dL [4.7‐10.4 g/dL]; P = .83). There was no significant difference in fibrinogen between horses with and without lymphoma (447 [100‐1364] mg/dL vs 433 [291‐2004] mg/dL; P = .47). On logistic regression, serum TK1 activity was not associated with a diagnosis of lymphoma (odds ratio, 0.97; 95% confidence interval, 0.9‐1.05, P = .48). Conclusion and Clinical Importance Serum TK1 values were not predictive of lymphoma diagnosis in this cohort of horses.

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Section: Discussionmentioning

confidence: 79%

Clinical performance of a commercially available thymidine kinase 1 assay for diagnosis of lymphoma in 42 hospitalized horses (2017‐2020)

Moore

Stefanovski

Luethy

2021

Veterinary Internal Medicne

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“…At the time of diagnosis, mild normocytic normochromic anemia was observed. This abnormality is not reported in MF without lymph node involvement in humans, or in animals [5,10,17,[24][25][26]. The recent infestation by tropical rat mites possibly explains the mild anemia as these mites are hematophagous and in case of a heavy infestation, can cause anemia [27].…”

Section: Discussionmentioning

confidence: 95%

Cutaneous epitheliotropic T-cell lymphoma in a donkey – a case report

Kondratjeva

Julien²,

Coutelier

et al. 2022

BMC Vet Res

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Background Cutaneous epitheliotropic T-cell lymphoma is a malignant tumour of the skin already reported in humans, dogs, cats, horses, and other species, but not previously in donkeys. The standard diagnosis is based on clinical, morphological and immunophenotypic data. Differentiation of malignant versus benign proliferation of lymphocytes is crucial; in ambiguous cases T-cell receptor gamma (TRG) molecular clonality should be tested. In the present paper, we report a case of mycosis fungoides diagnosed in a donkey whose diagnosis was based on clinical, histological and immunohistochemical aspects and a positive TRG clonality test. Case presentation A twenty-five-year-old donkey gelding was referred with a mildly pruritic, generalised and severe exfoliative dermatosis. Otherwise, the animal was clinically healthy, though mildly underweight. Dermatological examination revealed severe generalised alopecic and exfoliative dermatitis, occasionally eroded, with high number of large, thin, greyish scales. All mucocutaneous junctions except the hoofs were affected. Ectoparasites and dermatophytes were ruled out. The complete blood count and blood smear evaluation revealed mild normocytic normochromic anemia. The biochemistry panel showed mild hyperproteinemia with albumin within the normal range. Protein electrophoresis showed moderate polyclonal hypergammaglobulinemia. Histological findings were characterised by interface dermatitis with massive exocytosis in the epidermis of a homogenous population of lymphoid cells showing atypia. Clusters of neoplastic cells were present within the epidermis forming Pautrier “microabscesses”. These findings are consistent with cutaneous epitheliotropic lymphoma. Immunohistochemical staining revealed uniform labelling of the neoplastic cells for CD3, and lack of expression of CD20 (a B cell lineage associated marker). Molecular clonality PCR (PARR) was performed using equine TRG primers; this revealed a clonal rearrangement in a heavy polyclonal background. Transmission electronic microscopy showed multiple lymphocytes with convoluted or cerebriform nuclei. Conclusions This case report provides the first evidence of clinical, histopathological, immunophenotypic features, electron microscopy findings and molecular analysis of a cutaneous epitheliotropic T-cell lymphoma (mycosis fungoides) in a donkey. Our observations suggest that cutaneous T-cell lymphoma should be included in the differential diagnoses of exfoliative dermatitis, even those progressing in a chronic pattern and/or with few or no pruritus.

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“…Nucleoside analogues such as cytosine arabinoside, acyclovir and valacyclovir have already been used as chemotherapeutic agents in horses with lymphoma. Both acyclovir and valacyclovir were associated with complete or partial remission in selected cases of EHV-5-associated lymphoma [ 17 , 26 , 27 ]. Although the antiviral and anticancer nucleoside analogues tested here have not yet been used in clinical settings in equine practice to date, the results presented here suggest that they may be good candidates for the treatment of cancers, viral infections or a combination of both in horses.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of equine thymidine kinase 1 and preliminary evaluation of its suitability as a serum biomarker for equine lymphoma

Wang

Unger

Sharif

et al. 2021

BMC Mol and Cell Biol

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Background Thymidine kinase 1 (TK1) plays a key role in the synthesis of deoxythymidine triphosphate (dTTP) and is thus important for DNA replication and cell proliferation. The expression of TK1 is highest during S-phase, and it is rapidly degraded after mitosis. In cancer cells, TK1 is upregulated, resulting in leakage of excess TK1 into the blood. Consequently, serum TK1 has been used as a diagnostic and prognostic cancer biomarker, mainly in human medicine. The aims of this work were to characterize equine TK1 and to evaluate its suitability as a serum biomarker for equine lymphoma. Results Equine TK1 was cloned, expressed in E. coli and affinity purified. The purified recombinant horse TK1 showed broad substrate specificity, phosphorylating pyrimidine deoxyribo- and ribonucleosides and, to some extent, purine deoxynucleosides, including anticancer and antiviral nucleoside analogues. ATP was the preferred phosphate donor. Serum TK1 activity was measured in samples collected from horses with confirmed or suspected lymphoma and control horses with and without concurrent diseases. Serum TK1 activity levels were significantly higher in horses with lymphoma (p < 0.0005) and suspected lymphoma (p < 0.02) and in tumour-free groups with diverse diseases (p < 0.03) than in controls without concurrent diseases. There was a significant difference between the lymphoma group and the tumour-free group with diverse diseases (p < 0.0006). Furthermore, receiver operating characteristic analysis revealed a sensitivity of 0.86, a specificity of 0.95 and an AUC (area under the curve) of 0.92 compared to the controls without concurrent diseases, with a sensitivity of 0.97, a specificity of 0.71 and an AUC of 0.88 when compared with the tumour-free group with diverse diseases. Conclusion Equine TK1 showed high specific activity and broader substrate specificity than human TK1. Anticancer and antiviral thymidine analogues were efficiently phosphorylated by horse TK1, suggesting that these analogues might be good candidates for chemotherapy in horses. Serum TK1 activity was significantly higher in horses with lymphoma than in controls. ROC analysis indicated that serum TK1 could serve as a promising cancer biomarker in horses.

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Retrospective evaluation of clinical outcome after chemotherapy for lymphoma in 15 equids (1991‐2017)

Cited by 25 publications

References 25 publications

Clinical performance of a commercially available thymidine kinase 1 assay for diagnosis of lymphoma in 42 hospitalized horses (2017‐2020)

Clinical performance of a commercially available thymidine kinase 1 assay for diagnosis of lymphoma in 42 hospitalized horses (2017‐2020)

Cutaneous epitheliotropic T-cell lymphoma in a donkey – a case report

Molecular characterization of equine thymidine kinase 1 and preliminary evaluation of its suitability as a serum biomarker for equine lymphoma

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