Diffuse Small B-Cell Lymphoma: A High-Grade Malignancy

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Background: B-cell chronic lymphocytic leukemia (BCLL) in dogs generally is considered an indolent disease, but previous studies indicate a wide range in survival times.Objectives: We hypothesized that BCLL has a heterogeneous clinical course, similar to chronic lymphocytic leukemia in humans. We aimed to assess presentation and outcome in dogs with BCLL and evaluate the prognostic relevance of clinical and flow cytometric factors. Animals: One hundred and twenty-one dogs with BCLL diagnosed by flow cytometry. Three breed groups were represented: small breed dogs (n = 55) because of increased risk of BCLL; Boxers (n = 33) because of preferential use of unmutated immunoglobulin genes; and other breeds (n = 33). Methods: Retrospective study reviewing signalment, clinicopathologic data, physical examination findings, treatment, and survival of dogs with BCLL. Cellular proliferation, determined by the percentage of Ki67-expressing CD21+ B-cells by flow cytometry, was measured in 39 of 121 cases. Clinical and laboratory variables were evaluated for association with survival. Results:The median survival time (MST) for all cases was 300 days (range, 1-1644 days). Boxers had significantly shorter survival (MST, 178 days) than non-Boxers (MST, 423 days; P < .0001), and no significant survival difference was found between small breeds and other non-Boxer breeds. Cases with high Ki67 (>40% Ki67-expressing B-cells) had significantly shorter survival (MST, 173 days) than did cases with <40% Ki67 (MST undetermined; P = .03), regardless of breed. Cases with a high lymphocyte count (>60 000 lymphocytes/μL) or clinical signs at presentation had significantly shorter survival.Conclusions and Clinical Importance: B-cell chronic lymphocytic leukemia had a variable clinical course and Boxer dogs and cases with high Ki67 had more aggressive disease.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical outcome and prognostic factors in dogs with B‐cell chronic lymphocytic leukemia: A retrospective study

Rout

Labadie

Yoshimoto

et al. 2021

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“…Cases with DSBCL had a median OS of 140 days and only 4/22 cases achieved a CR. 5 Historically MZL was considered an indolent lymphoma, though some studies included both splenic and nodal MZL cases and outcomes are variable. 3,20,21 Older studies including small numbers of FL cases also suggested this subtype might have a more indolent course, 20,21 but a recent study evaluating 6 FL cases treated with chemotherapy found a median time to progression of 168 days and median lymphoma specific survival of 200 days.…”

Section: Clinical Outcome and Survival Analysismentioning

confidence: 99%

“…9 A subsequent study focused on small cell B-cell subtypes, defined by having a flow cytometry FS below the cutoff for DLBCL, found that the majority of cases were a provisional histologic subtype DSBCL, which has an aggressive clinical course (median survival time [MST] 140 days), suggesting some forms of small cell B-cell lymphoma have poorer outcomes than DLBCL. 5 This candidate DSBCL subtype does not correlate well with an established WHO classification and requires additional characterization and consensus as a diagnosis. Another study demonstrated that non-DLBCL B-cell lymphoma cases had significantly shorter survival (MST 114 days) and poorer response rates to treatment compared to DLBCL cases (MST 325 days).…”

Section: Introductionmentioning

confidence: 99%

“…B‐cell lymphomas are the most common phenotype diagnosed in dogs and diffuse large B‐cell lymphoma (DLBCL) is the most common subtype 1,2,4 . There are less common subtypes of B‐cell lymphoma that are comprised of small to intermediate‐sized B‐cells, including diffuse small B‐cell lymphoma (DSBCL), nodal marginal zone lymphoma (nMZL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and B‐cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) 5 . Less is known about the clinical presentation and outcome of these small cell B‐cell subtypes compared to DLBCL.…”

Section: Introductionmentioning

confidence: 99%

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Clinical outcome and Ki67 evaluation in dogs with nodal small cell B‐cell lymphoma diagnosed by flow cytometry

Rout

Fernandez

Yoshimoto

et al. 2022

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Background Nodal small cell B‐cell lymphoma subtypes in dogs cannot be distinguished by flow cytometry and information regarding treatment, prognosis, and outcome are limited. Hypothesis/Objectives Objectives were to describe outcome in dogs with nodal small cell B‐cell lymphoma diagnosed by flow cytometry and correlate clinical and laboratory data with survival. We hypothesized that B‐cell Ki67 expression measured by flow cytometry is associated with shorter progression free survival (PFS) and overall survival (OS). Animals Forty‐nine dogs with nodal small cell B‐cell lymphoma, defined by >80% CD21+ B‐cells by flow cytometry and small‐sized B‐cells by forward scatter. Methods Retrospective study reviewing treatment and outcome data extracted from medical records. Percentage of Ki67‐expressing B‐cells was measured by flow cytometry. Clinical, laboratory, and flow cytometry data were assessed for association with outcome. Results Median percentage of B‐cell Ki67 was 41% (range, 3%‐97%). Median PFS was 119 days and median OS was 222 days (n = 49). Among cases treated with CHOP‐based chemotherapy (n = 32), median PFS was 70 days, median OS was 267 days, and 50% of cases achieved complete response. Low percentage of B‐cell Ki67 (≤11%) was associated with prolonged OS by univariable analysis. Greater age, substage B, high B‐cell CD25 expression and low B‐cell CD21 and class II major histocompatibility complex expression by flow cytometry were independently associated with shorter OS. Conclusions and Clinical Importance Most nodal small cell B‐cell lymphoma cases had aggressive disease. Low Ki67 expression can help identify cases with better prognosis. Age, substage, and flow cytometry variables are useful prognostic factors.

Safety and biologic activity of a canine anti‐CD20 monoclonal antibody in dogs with diffuse large B‐cell lymphoma

McLinden,

Avery,

Gardner

et al. 2024

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BackgroundTo 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.AnimalsForty‐two client‐owned dogs with untreated B‐cell lymphoma.MethodsA 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.ResultsDogs 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.ConclusionsThe canine 1E4‐cIgGB anti‐CD20 monoclonal antibody is apparently safe when administered with doxorubicin and effectively depletes B‐cells in dogs with DLBCL.