Search

Background: To explore the safety and utility of combining low dose single‐agent doxorubicin with a canine specific anti‐CD20 monoclonal antibody (1E4‐cIgGB) in client owned dogs with untreated B‐cell lymphoma. Animals: Forty‐two client‐owned dogs with untreated B‐cell lymphoma. Methods: A prospective, single arm, open label clinical trial of dogs with B‐cell lymphoma were enrolled to receive 1E4‐cIgGB and doxorubicin in addition to 1 of 3 immunomodulatory regimens. B‐cell depletion was monitored by flow cytometry performed on peripheral blood samples at each visit. Results: Dogs demonstrated a statistically significant depletion in CD21+ B‐cells 7 days following the first antibody infusion (median fraction of baseline at 7 days = 0.04, P <.01) that persisted throughout treatment (median fraction of baseline at 21 days = 0.01, P <.01) whereas CD5+ T‐cells remained unchanged (median fraction of baseline at 7 days = 1.05, P =.88; median fraction of baselie at 7 days = 0.79, P =.42; Figure 1; Supplemental Table 3). Recovery of B‐cells was delayed, with at Day 196, only 6/17 dogs (35%) remaining on the study had CD21+ counts >0.5 of baseline, indicating sustained B cell depletion at 4+ months after the final treatment. 1E4‐cIgGB was well tolerated with only 1 dog exhibiting a hypersensitivity event within minutes of the last antibody infusion. Conclusions: The canine 1E4‐cIgGB anti‐CD20 monoclonal antibody is apparently safe when administered with doxorubicin and effectively depletes B‐cells in dogs with DLBCL. [ABSTRACT FROM AUTHOR]

Lymphoma diagnosis in dogs and cats is continually evolving as new subtypes and human correlates are being recognized. In humans, T-cell lymphomas with MUM1 expressed and plasma cell neoplasia or B-cell lymphomas with CD3 expressed aberrantly are reported only rarely. We report here a case series of tumors in dogs and cats with CD3 and MUM1 co-expressed as determined by immunocytochemistry or immunohistochemistry. Lineage was assigned for these tumors by 3 board-certified pathologists and a veterinary immunologist based on review of clinical and cellular features and the results of ancillary testing including PCR for antigen receptor rearrangements, flow cytometry, and serum protein electrophoresis with immunofixation. In cats, 7 of 7 tumors, and in dogs, 3 of 6 tumors with CD3 and MUM1 co-expressed had clonal rearrangement of the immunoglobulin gene or serum monoclonal immunoglobulin, consistent with a diagnosis of a plasma cell neoplasia or myeloma-related disorder with CD3 expressed aberrantly. Disease was often disseminated; notably, 3 of 7 feline cases had cutaneous and/or subcutaneous involvement in the tarsal area. In dogs, 3 of 6 cases had a clonal T-cell receptor gamma result and no clonal immunoglobulin gene rearrangement and were diagnosed as a T-cell tumor with MUM1 expressed. The use of multiple testing modalities in our series of tumors with plasma-cell and T-cell antigens in dogs and cats aided in the comprehensive identification of the lymphoproliferative disease subtype. [ABSTRACT FROM AUTHOR]

Canine acute leukaemia is a heterogeneous neoplasm with multiple phenotypes. Criteria to subtype acute leukaemia by flow cytometry have not been validated. The goal of this study was to develop a panel of antibodies and objective antigen expression criteria for the assignment of lymphoid or myeloid lineage by flow cytometry. We isolated mRNA from the blood of 45 CD34+ acute leukaemia cases and measured expression of 43 genes that represent lymphoid and myeloid lineages using NanoString technology. We determined differentially expressed genes between major groups identified by unsupervised hierarchical clustering. We then evaluated the expression of antigens by flow cytometry to determine if cases could be assigned to a lineage. Two groups were identified by gene expression. Group 1/LYMPH overexpressed lymphoid‐associated genes (ex. DNTT) and had a higher percentage of CD5 + CD3‐ cells by flow cytometry. Group 2/MYELO overexpressed myeloid‐associated genes (ex. ANPEP/CD13) and had a higher percentage of class II major histocompatibility complex (MHCII)‐ CD14+ and/or CD18 + CD4‐ cells. We proposed that >12.5% CD5 + CD3‐ cells in the blood was indicative of lymphoid lineage, and > 3.0% CD14 + MHCII‐ cells or > 18% CD18 + MHCII‐CD4‐ cells was indicative of myeloid lineage. 15/15 cases that met the proposed criteria for acute lymphocytic leukaemia were in LYMPH group and 12/15 cases that met the proposed criteria for acute myeloid leukaemia were in MYELO group. The majority of CD34+ cases that did not meet either immunophenotyping lineage criterion (12/13) clustered within the LYMPH group. In conclusion, currently available antibodies can be useful for determining canine acute leukaemia subtypes. [ABSTRACT FROM AUTHOR]

T‐cell leukemia/lymphoma accounts for roughly 30% of all types of lymphoproliferative neoplasia in dogs. Two forms of T‐cell lymphoma (T‐zone and peripheral T‐cell lymphoma) exhibit breed‐specific predilections. During the course of routine immunophenotyping, we observed a breed‐specific presentation of a unique form of T‐cell leukaemia in young English bulldogs. To describe the clinical presentation and outcome of a novel T‐cell leukaemia in English bulldogs and determine the frequency of this neoplasm in other breeds. The Clinical Hematopathology database, containing immunophenotyping data from peripheral blood of nearly 11 900 dogs, was queried for the phenotype observed in young English bulldogs: CD45+CD4−CD8−CD5+CD3+ class II major histocompatibility complex (MHC)‐low T‐cell leukaemia. Clinical presentation, treatment, and survival data were collected for a subset of cases. Fifty‐five English bulldog cases and 64 cases of other breeds were identified. No other breed was represented by >5 cases. Complete medical records were obtained for 50 bulldogs. Median age at diagnosis was 3 years and 76% of cases were male. Median lymphocyte count was 44 286 lymphocytes/μl (range, 1800–317 684/μl) and lymphocytes were described as small to intermediate‐sized. Many dogs were thrombocytopenic and had liver and spleen involvement, but not lymphadenopathy. Bulldogs that received multi‐agent chemotherapy had longer median survival times (83 days) compared to dogs that received no treatment (6 days) or less aggressive therapy (15 days) (p =.001). Non‐bulldogs had similar outcomes. CD4−CD8− class II MHC‐low T‐cell leukaemia has an aggressive clinical course and predilection for young English bulldogs. Breed‐specific presentation suggests an underlying genetic cause. [ABSTRACT FROM AUTHOR]

Background: Rabacfosadine (RAB, Tanovea‐CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs. Hypothesis/Objectives: To determine the efficacy and safety of RAB in dogs with lymphoma. Animals One hundred and fifty‐eight client‐owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019. Methods: Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression‐free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected. Results: The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P <.0001, HR 6.265 [95% CI 3.947‐9.945]). The BORR for RAB‐treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo‐treated dogs (P <.0001). One month after the last treatment, 37 RAB‐treated dogs (33%) were progression free compared with no placebo‐treated dogs (P <.0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB‐treated (20%) and 5 placebo‐treated dogs (13%). Conclusions and Clinical Importance: Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo. [ABSTRACT FROM AUTHOR]