In humans, pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The objective of this study was to evaluate the prognostic value of pretreatment D-dimer levels in dogs with high-grade lymphoma.

Forty-eight owned dogs with multicentric high-grade lymphoma were enrolled in a prospective and observational clinical study. Signalments, clinical findings, histology and cytology reports, immunophenotype, complete clinical staging and response to treatment were recorded for all dogs according to the WHO classification. Pretreatment D-dimer levels were measured with a quantitative D-dimer turbidimetric immunoassay (NycoCard Reader II, Nycomed).

Dogs were randomly assigned into two different treatment groups in a blinded fashion, for receiving anti-neoplastic drug (etoposide phosphate or F-14512). All dogs involved in the study followed the same protocol over a period of 8 weeks. The protocol consisted of four cycles of F14512 (0.075 mg/kg) or etoposide phosphate (100 mg/m²) IV injections every 2 weeks with a 3-hour injection once daily on 3 consecutive days. Short-term response was assessed by repeating complete staging at day 62, according to the RECIST criteria published for peripheral nodal lymphoma in dogs. Dogs were then followed every month until relapse. In case of relapse, a complementary CHOP-based chemotherapy protocol was proposed to the dog's owner.

The median value of pretreatment plasma D-dimer was 0.4 µg/mL (range: 0.1–14.3 µg/mL). The optimal cut-off value of D-dimer based on progressive free interval (PFI) was 0.5 µg/mL (HR: 2.22, p=0.014). A D-dimer level >0.5 µg/mL was significantly associated with inferior PFI (54 vs. 104 days, p=0.01). Dogs with a D-dimer level >0.5 µg/mL had a significantly worse survival than those with a D-dimer level ≤0.5 µg/mL (OS: 93 vs. 177 days, p=0.01). High D-dimer levels were not correlated with naïve vs. relapsed lymphoma, B vs. T lymphoma, clinical stage, substage and morphotype. High D-dimer levels remained an independent predictor for treatment received (etoposide phosphate vs. F14512, p=0.97). There was no difference in response rate and PFI between dogs treated with F-14512 vs. etoposide phosphate (ORR: 44% vs. 45%, p=0.92; PFI: 86 vs. 87.5 d, p=0.34, respectively).

In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in dogs with high-grade lymphoma. High pretreatment D-dimer levels were associated with short PFI and poor overall survival in 48 dogs enrolled in a prospective double-blind randomized clinical trial.

Disclosures

Disclosures to report
This study was conducted by Oncovet Clinical Research (OCR) as part of a collaborative research project between OCR and Pierre Fabre Medicament.