Canine acute leukaemia: 50 cases (1989-2014)

Abstract

Acute leukaemia (AL) is a bone marrow malignancy of hematopoietic progenitors that historically is poorly responsive to treatment. With the widespread adoption of dose-intense chemotherapy, more human patients attain long-term survivals, but whether comparable progress has been made in canine AL is unknown. To investigate this question, medical records from three academic veterinary hospitals were reviewed. Fifty dogs met the criteria for AL, having excess circulating or marrow blasts, a major cytopenia(s), and no substantial lymphadenopathy. Thirty-six dogs received cytotoxic chemotherapy; 23 achieved a complete or partial response for a median of 56 days (range, 9-218). With failure or relapse, 14 dogs were rescued. Median survival with treatment was poor at 55 days (range, 1-300). Untreated (n = 6) and palliatively-treated (n = 8) dogs lived a median of 7.5 days. Most dogs developed chemoresistance within weeks of initiating treatment, and consequently, survival times for AL remain disappointingly short.

Keywords: CHOP; acute leukaemia; canine; chemotherapy; immunophenotype.

Figure 1

Treatment selection and responses to cytotoxic chemotherapy in dogs with AL. (A) Slightly less than three-quarters of patients were treated with an injectable, cytotoxic chemotherapy protocol. (B) The objective response rate to induction cytotoxic chemotherapy was 64%. (C) Approximately two-fifths of patients that either failed induction chemotherapy or relapsed were administered one or more rescue protocols. (D) Half of 14 dogs responded to their first rescue. All 4 dogs subjected to additional attempts at rescue (two only [n=4] or three [n=1]) had short-lived, partial responses to these chemotherapy regimens (not depicted).

Figure 2

The durability of responses, outcomes and putative prognostic factors for dogs with AL treated with cytotoxic chemotherapy. (A) The first remission durations for patients that had objective responses to induction cytotoxic chemotherapy are shown. Two patients that were lost to follow-up while still in remission at 16 and 130 days are censored. The median duration was 56 days. (B) The survivals of all patients treated with cytotoxic chemotherapy are shown. Five patients were lost to follow-up at 16, 16, 72, 75 and 130 days and are censored. The median survival was 55 days. (C) The survivals of patients that had objective responses to cytotoxic chemotherapy are shown. Four patients were lost to follow-up at 16, 16, 72 and 130 days and are censored. The median survival was 79 days. In (A), (B) and (C), gray lines indicate 95% confidence intervals; ticks represent censored individuals. (D) There was no significant (ns) difference in survival between patients treated with cytotoxic chemotherapy (n=29) whose circulating lymphoblasts expressed surface CD34 at initial presentation versus those negative for the antigen (Mann-Whitney U test, p=0.6769). Peripheral lymphocyte/blast counts (E) in the 2nd and 3rd, but not 4th, quartiles were associated with significantly increased hazard for decreased survival in patients treated with cytotoxic chemotherapy. Increasing age at diagnosis (F) was not associated with a significantly greater hazard for poorer survival in treated dogs. For each variable, the patient population was divided into quartiles, represented by the median value depicted on the x-axis (lymphocyte/blast count [n=36]: 6,100; 63,510; 154,600; 321,948 cells/μL; age [n=35; the age of 1 dog was not recorded]: 3; 6.4; 8.2; 10.2 years). Survival curves for each quartile were then compared to the designated reference (lowest) quartile by log-ranktest, and computed hazard ratios and their 95% confidence intervals (Mantel-Haenszel method) were plotted on the y-axis.