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

Abstract

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.

Keywords: Ki67; canine; flow cytometry; immunophenotyping; lymphocytosis; lymphoma.

FIGURE 1

B‐cell CD25, class II MHC, and CD21 expression in BCLL cases compared to control B‐cells and comparison of B‐cell size in paired blood and lymph node samples from BCLL cases. A–C, Expression of CD25 (A), class II MHC (B) and CD21 (C) by flow cytometry is plotted for individual cases. Lines depict the median and interquartile range for each group. BCLL cases had significantly higher CD25 expression and significantly lower class II MHC expression than B‐cells from healthy controls. (D) Median forward light scatter of B‐cells is plotted for paired blood and lymph node samples from BCLL cases. B‐cells in the lymph node were significantly larger than those in the blood

FIGURE 2

Breed‐specific differences in lymphocyte count, B‐cell size, and B‐cell CD25 expression between Boxers and non‐Boxers with BCLL. Presenting lymphocyte count (A), B‐cell:neutrophil forward side scatter ratio (B), and B‐cell CD25 expression (C) are plotted for non‐Boxer and Boxer BCLL cases. Lines depict the median and interquartile range for each group. Boxers had significantly higher presenting lymphocyte counts and larger‐sized B‐cells than non‐Boxers. There was a significantly larger proportion of Boxer cases with very high CD25 expression (≥98% CD25‐expressing B‐cells) compared to non‐Boxers

FIGURE 3

B‐cell Ki67% expression measured by flow cytometry in control B‐cells, BCLL cases, and nodal B‐cell lymphoma cases (B‐cell size >500). The percentage of CD21+ B‐cells expressing Ki67 is on the vertical axis. Low Ki67 expression was defined as <20% Ki67‐expressing B‐cells and high Ki67 expression as >40% Ki67‐expressing B‐cells. The majority of non‐Boxer BCLL cases had <20% Ki67 and there was no significant difference in Ki67 expression between small breeds with increased BCLL risk, other small breeds, and non‐Boxer medium‐large breeds. Boxers with BCLL had significantly higher Ki67%. The vast majority of nodal B‐cell lymphoma cases (B‐cell size >500) had high Ki67 (>40%). Violin plots show the median (solid line) and quartiles (dashed lines) for each group

FIGURE 4

Kaplan–Meier curves showing overall survival in cases with BCLL. A, Boxers had significantly shorter survival than non‐Boxers. B, Cases with high Ki67 (>40%) had significantly shorter survival than cases with low‐intermediate Ki67 (<40%)