Serum C-reactive protein concentration as an indicator of remission status in dogs with multicentric lymphoma

BACKGROUND: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. OBJECTIVE: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. ANIMALS: Twenty-two dogs with untreated multicentric lymphoma. METHODS: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. RESULTS: Before therapy, a statistically significant majority of the dogs (P = .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P < .001). CRP concentrations of dogs in complete remission (median, 1.91; range, 0.2-103) were significantly different (P = .031) from those of dogs with partial remission (median, 2.48; range, 0-89), stable disease (median, 1.77; range, 1.03-42.65), or progressive disease (median, 8.7; range, 0-82.5). There was profound variation of CRP measurements within each dog. CONCLUSIONS: CRP is useful in determining complete remission status after treatment with cytotoxic drugs. However, the individual variation between dogs means CRP concentration is not sufficiently different in other remission states to permit its use in monitoring progression of the disease. Greater reliability in determining remission status might be achieved by combining CRP concentration with other serum markers.     

Utility of a multiple serum biomarker test to monitor remission status and relapse in dogs with lymphoma undergoing treatment with chemotherapy

A blinded retrospective study was conducted to investigate remission and recurrence of lymphoma in dogs receiving chemotherapy. The objective was to compare clinicians' assessment using palpation and cytology to the results of serum biochemical tests for haptoglobin (Hapt) and C‐reactive protein (C‐RP). These biochemical test results were combined using a diagnostic algorithm developed using data from 344 individual dogs. This multivariate approach, termed the canine lymphoma blood test (cLBT), was used to follow 57 dogs during and after treatment. cLBT of remission and recurrence compared well with clinicians' assessment and differentiated dogs in remission and those with recurring disease before appearance of lymphadenopathy (P < 0.001). The cLBT demonstrated prognostic potential based on pre‐treatment values on dogs with shorter survival times and on those achieving the lowest cLBT score during treatment that showed longer survival times. The test, therefore, demonstrates potential to assist in monitoring treatment of canine lymphoma.     

Evaluation of Single-Agent Mitoxantrone as Chemotherapy for Relapsing Canine Lymphoma

Many chemotherapeutic regimens will induce remission in dogs with lymphoma, but almost all dogs suffer relapse. Mitoxantrone was selected for evaluation as single-agent chemotherapy for relapsing canine lymphoma based on its use in humans undergoing salvage chemotherapy for non-Hodgkin's lymphoma and its tumoricidal effect against canine lymphoma. Dogs entered into study had multicentric lymphoma, and all had been treated solely with a standard combination chemotherapy protocol. At 1st relapse, all dogs were again staged and underwent lymph node biopsy. Mitoxantrone was administered IV at 6 mg/m² every 21 days. Dogs were evaluated for lymphadenopathy before each dose of mitoxantrone. Fifteen dogs were entered into study. The average age (±SEM) of the dogs studied was 7.7 ± 0.91 years, and most dogs were large (mean ± SEM weight, 24.44 ± 2.15 kg). Twelve dogs (80%) had B-cell lymphoma, and 3 had T-cell lymphoma. Dogs were staged IV (n = 12) or V (n = 3). The median duration of chemotherapy before entry into the study was 98 days. Overall median duration of response after mitoxantrone chemotherapy was 21 days. Complete responses were attained in 7 of 15 dogs (47%) with a median response duration of 84 days. Nine of 15 (60%) dogs attained a complete remission with additional chemotherapy after failing mitoxantrone chemotherapy. Mild toxicities were observed after mitoxantrone administration. No adverse reactions were observed during mitoxantrone infusions. The results of this study demonstrate that mitoxantrone, as a single agent, has limited value for dogs with lymphoma at 1st relapse after conventional multidrug chemotherapy.     

Monitoring of Minimal Residual Disease (MRD) after Multidrug Chemotherapy and Its Correlation to Outcome in Dogs with Lymphoma: A Proof‐of‐Concept Pilot Study

Background: Tumor cell burden in dogs with lymphoma cannot be assessed accurately by diagnostic evaluation during clinical complete remission (CR). Recent advances in polymerase chain reaction (PCR)‐based methods enabled us to quantify minimal residual disease (MRD) in canine lymphoma. Hypothesis/Objectives: To quantify MRD in dogs with lymphoma treated with multidrug chemotherapy and to correlate it with remission duration after chemotherapy. Animals: Seventeen dogs with lymphoma that achieved CR by multidrug chemotherapy. Methods: Rearranged immunoglobulin heavy chain or T‐cell receptor γ chain gene fragments from lymphoma cells were PCR amplified and sequenced to prepare clone‐specific primers and probes for real‐time PCR to quantify MRD. MRD in the peripheral blood was monitored during and at the end of a 25‐week multidrug chemotherapy protocol. Correlation between MRD at the end of chemotherapy and remission duration after chemotherapy was analyzed. Results: MRD gradually decreased after initiation of multidrug chemotherapy, reached a nadir as low as <0.019–1.0 cells/μL at weeks 4–17, and remained low or slightly increased until week 25. MRD at the end of chemotherapy was negatively correlated with remission duration from the end of chemotherapy to relapse. Conclusion and Clinical Importance: MRD could be an objective marker to indicate tumor cell burden in dogs with lymphoma even in clinical CR. MRD at the end of chemotherapy could be a prognostic factor to predict remission duration after chemotherapy.     

Increase in minimal residual disease in peripheral blood before clinical relapse in dogs with lymphoma that achieved complete remission after chemotherapy

Background: We developed previously a minimal residual disease (MRD) monitoring system in dogs with lymphoma by exploring a highly sensitive real‐time PCR system. Objectives: To identify the change in MRD before clinical relapse in dogs with lymphoma that achieved complete remission after chemotherapy. Animals: Twenty dogs with multicentric high‐grade B‐cell lymphoma. Methods: MRD levels in peripheral blood mononuclear cells (PBMCs) were measured by real‐time PCR amplifying the rearranged immunoglobulin heavy chain gene. MRD measurement and clinical assessment were performed every 2–4 weeks for 28–601 days after completion of chemotherapy. An increase in MRD was defined as an increase by more than 0.5, calculated by log₁₀[copy number of MRD per 10⁵ PBMCs], based on the uncertainty level observed in a canine lymphoma cell line. Results: During the follow‐up period, 15 dogs relapsed in 28–320 days (median, 120 days) after completion of chemotherapy. An increase in MRD was detected 2 weeks or more before relapse in 14 of the 15 dogs, but an increase in MRD before relapse could not be detected in the remaining 1 dog. The time from increased MRD to clinical relapse was 0–63 days (median, 42 days). In contrast, no increase in MRD was detected in 5 dogs that did not experience clinical relapse. Conclusion and Clinical Importance: An increase in MRD can be detected before clinical relapse in dogs with lymphoma. Application of early reinduction therapy based on an increase in MRD before clinical relapse may improve treatment outcome in canine lymphoma.     

Clonality and phenotyping of canine lymphomas before chemotherapy and during remission using polymerase chain reaction (PCR) on lymph node cytologic smears and peripheral blood

Polymerase chain reaction (PCR) assays for the immunoglobulin and T-cell receptor genes were utilized to determine phenotype and clonality from lymph node cytologic smears and peripheral blood lymphocytes from 10 dogs with lymphoma, before chemotherapy and during remission. Results were compared with those from 13 dogs with a cytologic diagnosis of lymph node hyperplasia. Clonality was identified in 7 of the lymphomas on the basis of either lymph node cytology or peripheral blood lymphocytes before treatment. No lymph node hyperplasia samples were clonal. In 6 of the dogs with lymphoma, clonality was demonstrated during clinical remission. Detection of PCR clonality during clinical remission is an effective means of identifying minimal residual disease in canine lymphoma and thus additional work is warranted to determine if molecular remission is prognostic or predictive for outcome in well-controlled and well-defined lymphoma subtypes.     

Sequential Low-Dose Rate Half-Body Irradiation and Chemotherapy for the Treatment of Canine Multicentric Lymphoma

Background: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels.
Hypothesis: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs.
Animals: Thirty-eight client-owned animals diagnosed with multicentric lymphoma.
Methods: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy.
Results: The median 1st remission was 410 days (95% confidence interval [CI] 241–803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334–1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%.
Conclusions and Clinical Relevance: Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.     

Assessment of cardiac troponin I (cTnI) and tissue velocity imaging (TVI) in 14 dogs with malignant lymphoma undergoing chemotherapy treatment with doxorubicin

Doxorubicin has been shown to be cardiotoxic at high doses but is an efficacious chemotherapeutic agent in the treatment of canine lymphoma. Echocardiographic measurements and serum ultrasensitive cardiac troponin I (cTnI) levels were obtained before and after doxorubicin administration in 14 dogs diagnosed with lymphoma. The aim of this prospective study was to evaluate changes in cTnI concentrations and tissue velocity imaging (TVI) values in dogs with lymphoma undergoing chemotherapy with doxorubicin. A total of 182 cTnI and 1017 TVI measurements were performed. Standard echocardiographic parameters, tissue Doppler indices and cTnI concentrations did not differ at any time point within a 12‐week cyclic combination protocol. In conclusion, the use of doxorubicin at standard doses in the treatment of canine lymphoma may not be associated with significant myocardial damage.     

Treatment of dogs with lymphoma using a 12-week, maintenance-free combination chemotherapy protocol

BACKGROUND: Treatment of lymphoma in dogs by long-term chemotherapy has favorable results. However, the efficacy of short-term, maintenance-free treatment protocols on remission and survival times in dogs has not been determined. HYPOTHESIS: That treatment using a 12-week chemotherapy protocol would be associated with satisfactory treatment outcome in dogs with lymphoma. ANIMALS: 77 dogs with histologically or cytologically confirmed diagnosis of lymphoma. METHODS: Prospective clinical trial in which dogs were treated with a 12-week chemotherapy protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and prednisolone. RESULTS: Complete remission rate was 76.3%. Multivariate logistic regression analysis revealed that clinical substage (P = .006) and immunophenotype (P = .003) had a significant influence on the likelihood of a dog achieving complete remission. Median duration of first complete remission was 243 days (range 19-1,191 days). The 6-month, 1-year, and 2-year remission rates were 68%, 28%, and 16%, respectively. In the multivariate analysis of patient variables, immunophenotype (P = .022) revealed a significant influence on first remission duration. Toxicosis was mild with the exception of 1 treatment-associated death. CONCLUSIONS AND CLINICAL IMPORTANCE: In this group of dogs the 12-week maintenance-free chemotherapy protocol was well tolerated and had satisfactory results.     

Retrospective analysis of factors affecting clinical outcome following CHOP‐based chemotherapy in dogs with primary nodal diffuse large B‐cell lymphoma

Numerous factors are known to affect the prognosis of dogs with chemotherapy‐treated lymphomas. However, prognostic factors for dogs with specific subtypes of lymphoma are less clearly defined. The objective of this study was to identify prognostic factors for dogs receiving CHOP‐based chemotherapy for primary nodal diffuse large B‐cell lymphoma (DLBCL). Medical records of dogs treated for DLBCL at the Purdue Veterinary Teaching Hospital (PUVTH) from 2006 to 2016 were reviewed. Factors potentially related to prognosis were analysed using multivariable statistical methods. Ninety‐eight dogs were included in the study. Best overall response to chemotherapy was complete remission in 80 dogs (81.6%) and partial remission in 18 dogs (18.4%). Median progression‐free survival (PFS) for the entire population was 252 days (range 19‐1068). Factors significantly associated with achieving partial (rather than complete) remission following CHOP included presence of thrombocytopenia at diagnosis (OR 6.88; 95% CI 1.98‐23.93; P = .002), baseline serum globulin concentration (OR 2.63; 95% CI 1.03‐6.75; P = .044), and age at diagnosis (OR 1.36; 95% CI 1.08‐1.71; P = .009). Factors significantly associated with PFS in the lowest quartile (≤93 days) included presence of thrombocytopenia at diagnosis (OR 8.72; 95% CI 1.54‐49.33; P = .014), age at diagnosis (OR 1.47; 95% CI 1.12‐1.94; P = .005), and baseline neutrophil count (OR 1.18; 95% CI 1.02‐1.37; P = .025). Presence of thrombocytopenia, greater age, higher neutrophil count, and higher serum globulin concentration all may be associated with a particularly poor outcome in dogs receiving CHOP‐based chemotherapy for DLBCL.     

Evaluation of a Multidrug Chemotherapy Protocol (ACOPA II) in Dogs With Lymphoma

A chemotherapeutic protocol using cyclophosphamide, vincristine, prednisone, doxorubicin, and L-asparaginase (ACOPA II) was evaluated in dogs with lymphoma. The response rate for 68 dogs treated with ACOPA II (complete remission [CR] 65%, partial remission [PR] 10%) was lower than that for 41 dogs treated with a related protocol previously evaluated (ACOPA I; CR 76%, PR 12%). Initial treatment with doxorubicin and prednisone did not decrease the prevalence or severity of toxicity during induction. The mortality during induction was 22%. The median duration of CR for dogs treated with ACOPA II was 9 months, with 40% still in remission at 1 year and 21% at 2 years. The rate of CR was lower for dogs with signs of illness at presentation (substage b ) and for dogs weighing less than 15 kg. Age was negatively correlated with survival time and duration of remission. Dogs with immunoblastic lymphoma had a more favorable prognosis than did those with lymphoblastic lymphoma. Survival times were also longer for dogs in substage a at presentation. Seven dogs in which treatment was discontinued while in remission had comparable remission duration to that achieved by dogs receiving long-term maintenance chemotherapy.     

Preliminary assessment of serum clusterin as a potential biomarker for canine lymphoma

Clusterin (CLU), also known as apolipoprotein J, is a widely expressed, heterodimeric, glycoprotein, important in tumourigenesis, apoptosis and immunoregulation. In humans, CLU expression has been associated with anaplastic large cell and Hodgkin's lymphoma. In this study, serum CLU levels in dogs with multicentric lymphoma (MLSA) were compared with healthy control dogs, using both western blot and enzyme‐linked immunosorbent assay (ELISA). Western blot confirmed the presence of CLU in dog sera at the predicted molecular weight and the relative levels detected correlated with the levels detected by ELISA. CLU level analysis by ELISA found treatment naïve dogs with MLSA had a significantly (P < .001) lower serum CLU level compared with healthy controls. However, there was no significant difference between MLSA dogs prior to treatment and in complete remission. The wide variation in serum CLU levels may limit its potential as a single candidate biomarker for MLSA, although any prognostic predictive value of serum CLU concentrations has yet to be assessed.     

Assessment of corticosteroid-induced alkaline phosphatase as a prognostic indicator in canine lymphoma

OBJECTIVES: To examine the incidence of elevated corticosteroid-induced alkaline phosphatase (sALP) in dogs with lymphoma and to determine if sALP is a reliable prognostic indicator in canine lymphoma. METHODS: The medical records of 62 canine lymphoma patients treated with a combination chemotherapy protocol from 1994 to 2003 at the University of Illinois Veterinary Teaching Hospital were examined. Variables assessed with respect to response rate and remission duration included age, bodyweight, sex, breed, World Health Organization stage (I to V), substage (a or b), pretreatment administration of corticosteroid, and serum levels of alkaline phosphatase, sALP and alanine aminotransferase. RESULTS: sALP was not statistically significant with respect to response rate or duration of remission, nor was preinduction glucocorticoid administration. Stage was significant with respect to achieving remission. CLINICAL SIGNIFICANCE: It was found that sALP is not a useful prognostic indicator for response rate and remission duration in dogs with lymphoma.     

Evaluation of the effects of dietary n-3 fatty acid supplementation on the pharmacokinetics of doxorubicin in dogs with lymphoma

OBJECTIVE: To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma. ANIMALS: 23 dogs with lymphoma in stages IIIa, IVa, and Va. PROCEDURE: Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans. RESULTS: No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.     

Serum alpha 1-acid glycoprotein concentrations before and after relapse in dogs with lymphoma treated with doxorubicin

OBJECTIVE: To determine whether serum alpha 1-acid glycoprotein (AGP) concentration was a useful marker of relapse in dogs with lymphoma that were in clinical remission following treatment with doxorubicin. DESIGN: Cohort study. ANIMALS: 12 dogs with lymphoma and 10 healthy dogs. PROCEDURE: Serum AGP concentration was measured in the healthy dogs and in the dogs with lymphoma before treatment, 3 weeks after the first dose of doxorubicin was administered, and every 3 weeks thereafter until relapse (i.e., recurrence of clinically detectable disease such as palpable enlargement of peripheral lymph nodes). Serum AGP concentrations were determined by use of a radial immunodiffusion kit. RESULTS: Mean serum AGP concentration in healthy dogs was significantly less than concentration in dogs with lymphoma prior to treatment. Mean serum AGP concentrations after the first and each subsequent dose of doxorubicin were not significantly different from concentration in healthy dogs. However, mean serum AGP concentrations 3 weeks prior to and at the time of relapse were significantly higher than concentration measured after the first dose of doxorubicin, and were not significantly different from concentration measured before treatment. CLINICAL IMPLICATIONS: Results suggest that measuring serum AGP concentration may be a useful method of predicting relapse before recurrence of clinically detectable disease in dogs with lymphoma undergoing treatment with doxorubicin.     

Evaluation of serum interleukin 2 receptor and beta-2-microglobulin as prognostic factors for canine lymphoma: A pilot study

Interleukin 2 receptor (IL-2R) is released from activated T cell lymphocytes and related to proliferation of B cells and T cells. Beta-2-microglobulin (B2M) is synthesized from all nucleated cells and constitutes a major histocompatibility complex class I antigen. In human medicine, high concentrations of these two factors have been found to be related to prognosis in aggressive non-Hodgkin's lymphoma. In this pilot study, we aimed to assess the correlation between the serum concentration of IL-2R and B2M and the diagnosis and prognosis of canine lymphoma. This study included 8 healthy dogs and 17 dogs with lymphoma. To measure the serum concentration of IL-2R and B2M, a commercial enzyme-linked immunosorbent assay was used. In dogs with lymphoma, IL-2R concentrations were significantly high at the time of diagnosis, but B2M concentrations were not. In relapsed dogs, both IL-2R and B2M concentrations were significantly higher than those in the control and chemotherapy response groups. When the serum concentrations of IL-2R and B2M during chemotherapy were monitored in four relapsed dogs, B2M levels were more closely related with relapse. This study demonstrated that serum IL-2R and B2M concentration can be a diagnostic or prognostic tool for canine lymphoma. Monitoring of serum B2M concentration seems to be useful for predicting relapse.     

Serum thymidine kinase 1 activity as a prognostic biomarker in dogs with chemotherapy-treated diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is frequently treated with chemotherapy incorporating cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), which induces remission in 80% to 95% of cases. However, not all dogs derive meaningful benefit from CHOP, and prognostic factors for dogs with DLBCL are poorly defined. Serum thymidine kinase 1 (TK1) activity, a marker of tumour cell proliferation, has shown promising initial results as a prognostic biomarker in dogs with multicentric lymphomas. The purpose of this study was to determine if baseline serum TK1 activity is associated with clinical outcome in dogs with CHOP-treated DLBCL. Baseline serum TK1 activity was measured in banked sera from 98 dogs with CHOP-treated DLBCL using a commercially available ELISA kit. Data on other potential prognostic factors were abstracted retrospectively from electronic medical records. Multivariable statistical methods were used to identify associations between TK1 and other potential prognostic factors with progression-free survival (PFS) and attainment of complete remission. TK1 activity at baseline was not associated with PFS (p = .299) or attainment of complete remission (p = .910) following CHOP chemotherapy. Of the other prognostic factors analysed, only purebred (vs. mixed breed) status (HR 8.81, 95% CI 1.68–46.30, p = .010), attainment of complete (vs. partial) remission (HR 0.09, 95% CI 0.02–0.49, p = .006), and baseline serum C-reactive protein concentration (HR 1.19, 95% CI 1.07–1.32, p = .001) were independently associated with PFS. Based on these findings, baseline serum TK1 activity does not appear to be a useful prognostic biomarker in dogs with CHOP-treated DLBCL.     

A combination chemotherapy protocol with MOPP and CCNU consolidation (Tufts VELCAP-SC) for the treatment of canine lymphoma

A chemotherapy protocol using a consolidation phase of alkylating agents was used for treating 94 dogs with lymphoma. Fifty‐seven percent of dogs were in stage V, 63% were ill and 38% had T‐cell lymphoma. The complete remission (CR) rate was 70% and is comparable to results achieved with previously published chemotherapy protocols. Anorexia predicted the remission; of the 40 dogs without anorexia, 35 (88%) achieved CR whereas of 52 dogs with anorexia, 30 (58%) achieved CR. Median first CR duration was 168 days and 1‐ and 2‐year CR rates were 17.4 and 15.5%, respectively. Platelet count affected length of first CR, with a 53.2% reduced chance of coming out of remission with each log increase in platelet count. Median survival time was 302 days. One and 2‐year survival rates were 44 and 13%, respectively. Anorexia and no dose reduction of any drug were independent negative variables. Of 93 dogs with toxicity data, 65 dogs (70%) required a dose reduction. Cyclophosphamide was most commonly reduced with reductions in 31 (38%) of 82 dogs. A dose reduction was significantly more likely in dogs with B‐cell lymphoma than in those with T‐cell lymphoma.     

Antioxidant Status and Biomarkers of Oxidative Stress in Dogs with Lymphoma

Background: Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly diagnosed lymphoma before treatment and once in remission, with comparison with healthy controls.
Hypothesis: Dogs with lymphoma have increased oxidant and reduced antioxidant concentrations compared with healthy controls, and that these abnormalities normalize once remission is achieved.
Animals: Seventeen dogs with lymphoma and 10 healthy controls.
Methods: Prospective, observational study. Measures of oxidative stress [malondialdehyde and total isoprostanes (isoP)] and antioxidants [α-tocopherol, γ-tocopherol, oxygen radical absorbance capacity (ORAC), and glutathione peroxidase (GSHPx)] were assessed in dogs with newly diagnosed lymphoma before treatment compared with healthy control dogs. The same parameters were measured in the dogs with lymphoma on week 7 of the chemotherapy protocol when all dogs were in remission.
Results: At baseline, dogs with lymphoma had significantly lower α-tocopherol ( P <.001) and γ-tocopherol ( P = .003) but higher GSHPx ( P = .05), ORAC ( P = .001), and isoP ( P < .001) compared with healthy controls. In the dogs with lymphoma, α-tocopherol concentrations were higher ( P = .005) and ascorbic acid were lower ( P = .04) after treatment.
Conclusions and Clinical Importance: Results suggest that dogs with lymphoma have alterations in oxidant and antioxidant concentrations and that the status of some of these biomarkers normalize after remission. Further studies are warranted to determine whether antioxidant interventions to correct these are beneficial in the treatment of canine lymphoma.     

Evaluation of an actinomycin-D-containing combination chemotherapy protocol with extended maintenance therapy for canine lymphoma

In this retrospective study, a 6-drug (prednisone, L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and actinomycin-D) chemotherapy protocol with extended maintenance for the treatment of lymphoma was evaluated for efficacy and toxicity in 39 dogs. The complete remission rate was 97%, with a median progression-free survival (PFS) of 331 d. The median overall survival (OS) was 461 d. Of the variables evaluated for prognostic significance, only immunophenotype and sex were found to be prognostic. Dogs with T-cell lymphoma had shorter PFS and OS than dogs with B-cell lymphoma. Castrated male dogs had a shorter PFS and OS than spayed female dogs. Although the majority of dogs experienced one or more episodes of chemotherapy associated toxicity, the majority of these episodes were mild and self-limiting. The results of this study warrant further investigation into the value of extended maintenance therapy and inclusion of actinomycin-D in combination chemotherapy protocols for canine lymphoma.