DOI
https://doi.org/10.18849/ve.v7i1.381Abstract
PICO question
In dogs with B-cell lymphoma, does the use of flow cytometry provide useful prognostic information?
Clinical bottom line
Category of research question
Prognosis
The number and type of study designs reviewed
Twelve papers were critically reviewed. All were cohort studies
Strength of evidence
Moderate
Outcomes reported
There are multiple potential prognostic indicators in canine B-cell lymphoma that flow cytometry can be used to evaluate, including lymphoma stage, survival time and time to progression. There is promising evidence for the use of percentage expression of CD25 and Ki67 cellular markers in providing prognostic information in canine B-cell lymphoma and these should be assessed further in clinical practice. Flow cytometry has also been shown to be useful in assessing bone marrow infiltration and providing prognostic information relating to this. There is also evidence for the prognostic value of measuring expression of class II MHC and CTLA-4 cellular markers, peripheral lymphocyte / monocyte ratio, nodal regulatory T-cell populations and the ratio between T and B lymphocytes in extranodal locations. Peripheral regulatory T-cell populations and cellular size were also assessed, however further investigations are required before confirming their prognostic value
Conclusion
Flow cytometric analysis offers useful measures of prognosis in canine B-cell lymphoma, although further validation is required before introducing their routine use. Percentage expression of CD25 and Ki67 cellular markers from lymph node aspirates of dogs with B-cell lymphoma appear to be promising prognostic indicators in clinical investigations, however this needs to be translated into clinical practice. While there is evidence for the prognostic value of bone marrow infiltration measured flow cytometrically, expression of class II MHC and CTLA-4, peripheral lymphocyte / monocyte ratio, nodal regulatory T-cell populations and the ratio between T and B lymphocytes in extranodal locations, these need to be further investigated before introducing into clinical practice. As new antibodies against cellular targets in dogs become available, it is likely that flow cytometry will become even more useful in providing prognostic information
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
References
Baek, D. S., Chung, T. H., Kim, Y. H., Oh, S. K., So, K. M. & Park, C. (2017). Changes in regulatory T-cells in dogs with B-cell lymphoma and association with clinical tumour stage. Veterinarni Medicina. 62(12), 647–653. DOI: https://doi.org/10.17221/7/2015-VETMED
Fournel-Fleury, C., Magnol, J. P., Bricaire, P., Marchal, T., Chabanne, L., Delverdier, A., Bryon, P.A. & Felman, P. (1997). Cytohistological and immunological classification of canine malignant lymphomas: Comparison with human non-Hodgkin's lymphomas. Journal of Comparative Pathology. 117(1), 35–59. DOI: https://doi.org/10.1016/S0021-9975(97)80065-5
Joetzke, A. E., Eberle, N., Nolte, I., Mischke, R. & Simon, D. (2012). Flow cytometric evaluation of peripheral blood and bone marrow and fine-needle aspirate samples from multiple sites in dogs with multicentric lymphoma. American Journal of Veterinary Research. 73(6), 884–893. DOI: https://doi.org/10.2460/ajvr.73.6.884
Li, Y.-L., Pan, Y.-Y., Jiao, Y., Ning, J., Fan, Y.-G. & Zhai, Z.-M. (2014). Peripheral blood lymphocyte/monocyte ratio predicts outcome for patients with diffuse large B-cell lymphoma after standard first-line regimens. Annals of Hematology. 93(4), 617–626. DOI: https://doi.org/10.1007/s00277-013-1916-9
Lowenthal, J. W., Zubler, R. H., Nabholz, M. & MacDonald, H.R. (1985). Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. Nature. 315(6021), 669–672. DOI: https://doi.org/ 10.1038/315669a0
Marconato, L. (2011). The staging and treatment of multicentric high-grade lymphoma in dogs: A review of recent developments and future prospects. The Veterinary Journal. 188(1), 34–38. DOI: https://doi.org/10.1016/j.tvjl.2010.04.027
Marconato, L., Martini, V., Aresu, L., Sampaolo, M., Valentini, F., Rinaldi, V. & Comazzi, S. (2013). Assessment of bone marrow infiltration diagnosed by flow cytometry in canine large B-cell lymphoma: Prognostic significance and proposal of a cut-off value. The Veterinary Journal. 197(3), 776–781. DOI: https://doi.org/10.1016/j.tvjl.2013.05.003
Marconato, L., Martini, V., Stefanello, D., Moretti, P., Ferrari, R., Comazzi, S., Laganga, P., Riondato, F. & Aresu, L. (2015). Peripheral blood lymphocyte/monocyte ratio as a useful prognostic factor in dogs with diffuse large B-cell lymphoma receiving chemoimmunotherapy. The Veterinary Journal. 206(2), 226–230. DOI: https://doi.org/10.1016/j.tvjl.2015.07.009
Mizutani, N., Goto-Koshino, Y., Tsuboi, M., Kagawa, Y., Ohno, K., Uchida, K. & Tsujimoto, H. (2016). Evaluation of CD25-positive cells in relation to the subtypes and prognoses in various lymphoid tumours in dogs. Immunopathology. 173, 39–43. DOI: https://doi.org/10.1016/j.vetimm.2016.03.018
Owen, L. N. & World Health Organization (1980). TNM Classification of Tumours in Domestic Animals. N. Owen, ed. (No. VPH/CMO/80.20). Geneva: World Health Organization. [online] Available from: https://apps.who.int/iris/bitstream/handle/10665/68618/VPH_CMO_80.20_eng.pdf [Accessed 1 June 2020].
Pinheiro, D., Chang, Y.-M., Bryant, H., Szladovits, B., Dalessandri, T., Davison, L. J., Yallop, E., Mills, E., Leo, C., Lara, A.,Stell, A. Polton, G. & Garden, O. A. (2014). Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: Evidence of a negative prognostic impact of FOXP3+ T-cells in canine B-cell lymphoma. PloS One. 9(8), 105027. DOI: https://doi.org/1371/journal.pone.0105027
Poggi, A., Miniscalco, B., Morello, E., Comazzi, S., Gelain, M. E., Aresu, L. & Riondato, F. (2015). Flow cytometric evaluation of ki67 for the determination of malignancy grade in canine lymphoma. Veterinary and Comparative Oncology. 13(4), 475–480. DOI: https://doi.org/10.1111/vco.12078
Poggi, A., Miniscalco, B., Morello, E., Gattino, F., Delaude, A., Ferrero Poschetto, L., Aresu, L., Gelain, M. E., Martini, V., Comazzi, S. and Riondato, F. (2017). Prognostic significance of Ki67 evaluated by flow cytometry in dogs with high‐grade B‐cell lymphoma. Veterinary and Comparative Oncology. 15(2), 431–440. DOI: https://doi.org/10.1111/vco.12184
Ponce, F., Marchal, T., Magnol, J. P., Turinelli, V., Ledieu, D., Bonnefont, C., Pastor, M., Delignette, M. L. & Fournel-Fleury, C. (2010). A morphological study of 608 cases of canine malignant lymphoma in France with a focus on comparative similarities between canine and human lymphoma morphology. Veterinary Pathology. 47(3), 414–433. DOI: https://doi.org/10.1177/0300985810363902
Rao, S., Lana, S., Eickhoff, J., Marcus, E., Avery, P. R., Morley, P. S. & Avery, A. C. (2011). Class II major histocompatibility complex expression and cell size independently predict survival in canine B‐cell lymphoma. Journal of Veterinary Internal Medicine. 25(5), 1097–1105. DOI: https://doi.org/10.1111/j.1939-1676.2011.0767.x
Riondato, F., Martini, V., Melega, M., Poggi, A. & Miniscalco, B. (2021). Variation of apoptotic and proliferative activity among lymphoma subtypes in dogs: A flow cytometric study. Research in Veterinary Science. 135, 324–328. DOI: https://doi.org/10.1016/j.rvsc.2020.10.008
Schlüter, C., Duchrow, M., Wohlenberg, C., Becker, M. H., Key, G., Flad, H. D. & Gerdes, J. (1993). The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. Journal of Cell Biology. 123(3), 513–522. DOI: https://doi.org/10.1083/jcb.123.3.513
Tagawa, M., Kurashima, C., Takagi, S., Maekawa, N., Konnai, S., Shimbo, G., Matsumoto, K., Inokuma, H., Kawamoto, K. & Miyahara, K. (2018). Evaluation of costimulatory molecules in dogs with B-cell high grade lymphoma. PloS One. 13(7). DOI: https://doi.org/10.1371/journal.pone.0201222
Vail, D. M., Michels, G. M., Khanna, C., Selting, K. A., London, C. A. & Veterinary Cooperative Oncology Group (2010). Response evaluation criteria for peripheral nodal lymphoma in dogs (v1. 0)–a Veterinary Cooperative Oncology Group (VCOG) consensus document. Veterinary and Comparative Oncology. 8(1), 28–37. DOI: https://doi.org/10.1111/j.1476-5829.2009.00200.x
Wolf‐Ringwall, A., Lopez, L., Elmslie, R., Fowler, B., Lori, J., Sfiligoi, G., Skope, A., Arnold, E., Hughes, K. L., Thamm, D. H. & Ehrhart III, E. J., Avery, A. C. & Lana, S. E. (2019). Prospective evaluation of flow cytometric characteristics, histopathologic diagnosis and clinical outcome in dogs with naïve B‐cell lymphoma treated with a 19‐week CHOP protocol. Veterinary and Comparative Oncology. 18(3), 342–352. DOI: https://doi.org/10.1111/vco.12553
Yang, S.-C., Hillinger, S., Riedl, K., Zhang, L., Zhu, L., Huang, M., Atianzar, K., Kuo, B. Y., Gardner, B., Batra, R. K., Strieter, R. M., Dubinett S. M. &Sharma, S. (2004). Intratumoral administration of dendritic cells overexpressing CCL21 generates systemic antitumor responses and confers tumor immunity. Clinical Cancer Research. 10(8), 2891–2901. DOI: https://doi.org/10.1158/1078-0432.CCR-03-0380
License
Copyright (c) 2022 Benjamin Haythornthwaite
This work is licensed under a Creative Commons Attribution 4.0 International License.
Veterinary Evidence uses the Creative Commons copyright Creative Commons Attribution 4.0 International License. That means users are free to copy and redistribute the material in any medium or format. Remix, transform, and build upon the material for any purpose, even commercially - with the appropriate citation.
Most read articles by the same author(s)
- Benjamin Haythornthwaite, Comparison of the safety of alfaxalone and propofol as anaesthetic induction agents in bitches undergoing c-section , Veterinary Evidence: Vol. 5 No. 3 (2020): The third issue of 2020
