Editorial Type:
Oncology

Evaluation of vincristine-associated myelosuppression in Border Collies

Denise L. Lind Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

Search for other papers by Denise L. Lind in
Current site
Google Scholar
PubMed Close
 PhD, DVM
,
Janean L. Fidel Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

Search for other papers by Janean L. Fidel in
Current site
Google Scholar
PubMed Close
 DVM, MS
,
John M. Gay Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

Search for other papers by John M. Gay in
Current site
Google Scholar
PubMed Close
 DVM, PhD
, and
Katrina L. Mealey Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

Search for other papers by Katrina L. Mealey in
Current site
Google Scholar
PubMed Close
 DVM, PhD
DOI:
https://doi.org/10.2460/ajvr.74.2.257
Volume/Issue:
Volume 74: Issue 2
Online Publication Date:
01 Feb 2013
Restricted access
Sign In Reprints and Permissions Purchase Article

Abstract

Objective—To determine whether Border Collies (ATP binding cassette subfamily B1 gene [ABCB1] wildtype) were more likely than other breeds to develop vincristine-associated myelosuppression (VAM) and, if so, whether this was caused by a mutation in ABCB1 distinct from ABCB1-1Δ.

Animals—Phase 1 comprised 36 dogs with the ABCB1 wildtype, including 26 dogs with lymphoma (5 Border Collies and 21 dogs representing 13 other breeds) treated with vincristine in a previous study; phase 2 comprised 10 additional Border Collies, including 3 that developed VAM and 7 with an unknown phenotype.

Procedures—For phase 1, the prevalence of VAM in ABCB1-wildtype Border Collies was compared with that for ABCB1-wildtype dogs of other breeds with data from a previous study. For phase 2, additional Border Collies were included. Hematologic adverse reactions were graded with Veterinary Co-operative Oncology Group criteria. Genomic DNA was used to amplify and sequence all 27 exons of the canine ABCB1. Sequences from affected dogs were compared with those of unaffected dogs and dogs of unknown phenotype.

Results—3 of 5 Border Collies with the ABCB1 wildtype developed VAM; this was significantly higher than the proportion of other dogs that developed VAM (0/21). A causative mutation for VAM in Border Collies was not identified, although 8 single nucleotide polymorphisms in ABCB1 were detected.

Conclusions and Clinical Relevance—Breed-associated sensitivity to vincristine unrelated to ABCB1 was detected in Border Collies. Veterinarians should be aware of this breed predisposition to VAM. Causes for this apparent breed-associated sensitivity should be explored.

Abstract

Objective—To determine whether Border Collies (ATP binding cassette subfamily B1 gene [ABCB1] wildtype) were more likely than other breeds to develop vincristine-associated myelosuppression (VAM) and, if so, whether this was caused by a mutation in ABCB1 distinct from ABCB1-1Δ.

Animals—Phase 1 comprised 36 dogs with the ABCB1 wildtype, including 26 dogs with lymphoma (5 Border Collies and 21 dogs representing 13 other breeds) treated with vincristine in a previous study; phase 2 comprised 10 additional Border Collies, including 3 that developed VAM and 7 with an unknown phenotype.

Procedures—For phase 1, the prevalence of VAM in ABCB1-wildtype Border Collies was compared with that for ABCB1-wildtype dogs of other breeds with data from a previous study. For phase 2, additional Border Collies were included. Hematologic adverse reactions were graded with Veterinary Co-operative Oncology Group criteria. Genomic DNA was used to amplify and sequence all 27 exons of the canine ABCB1. Sequences from affected dogs were compared with those of unaffected dogs and dogs of unknown phenotype.

Results—3 of 5 Border Collies with the ABCB1 wildtype developed VAM; this was significantly higher than the proportion of other dogs that developed VAM (0/21). A causative mutation for VAM in Border Collies was not identified, although 8 single nucleotide polymorphisms in ABCB1 were detected.

Conclusions and Clinical Relevance—Breed-associated sensitivity to vincristine unrelated to ABCB1 was detected in Border Collies. Veterinarians should be aware of this breed predisposition to VAM. Causes for this apparent breed-associated sensitivity should be explored.

Contributor Notes

Dr. Lind's present address is Banfield Pet Hospital, 10210 59th Ave SW, Lakewood, WA 98499.

Supported by the Veterinary Clinical Pharmacology Laboratory, College of Veterinary Medicine, Washington State University. Dr. Lind was supported in part by a Washington State University College of Veterinary Medicine Summer Student Research Fellowship Program.

A portion of the results was presented as part of a course in the professional veterinary curriculum at Washington State University.

Address correspondence to Dr. Mealey (kmealey@vetmed.wsu.edu).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Feb 2013

  • 1. Chun R. Lymphoma: which chemotherapy protocol and why? Top Companion Anim Med 2009; 24: 157–162.

  • 2. Rebhun RB, Kent MS, Borrofka SA, et al. CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma. Vet Comp Oncol 2011; 9: 38–44.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 3. Tomiyasu H, Takahashi M, Fujino Y, et al. Gastrointestinal and hematologic adverse events after administration of vincristine, cyclophosphamide and doxorubicin in dogs with lymphoma that underwent a combination multidrug chemotherapy protocol. J Vet Med Sci 2010; 72: 1391–1397.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 4. Kaiser CI, Fidel JL, Roos M, et al. Reevaluation of the University of Wisconsin 2-year protocol for treating canine lymphosarcoma. J Am Anim Hosp Assoc 2007; 43: 85–92.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 5. Thamm DH, Vail DM. Aftershocks of cancer chemotherapy: managing adverse effects. J Am Anim Hosp Assoc 2007; 43: 1–7.

  • 6. Van Schaik RH. CYP450 pharmacogenetics for personalizing cancer therapy. Drug Resist Update 2008; 11: 77–98.

  • 7. Mealey KL, Fidel J, Gay JM, et al. ABCB1-1D polymorphism can predict hematologic toxicity in dogs treated with vincristine. J Vet Intern Med 2008; 22: 996–1000.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 8. Song S, Suzuki H, Kawai R, et al. Effect of PSC 833, a P-glycoprotein modulator, on the disposition of vincristine and digoxin in rats. Drug Metab Dispos 1999; 27: 689–694.

    • Search Google Scholar
    • Export Citation

  • 9. Veterinary Co-operative Oncology Group. Common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy of biological antineoplastic therapy in dogs and cats v1.0. Vet Comp Oncol 2004; 2: 195–213.

    • Search Google Scholar
    • Export Citation

  • 10. Han JI, Son HW, Park SC, et al. Novel insertion mutation of a BCB1 gene in an ivermectin-sensitive Border Collie. J Vet Sci 2010; 11: 341–344.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 11. Mealey KL, Jabbes M, Spencer E, et al. Differential expression of CYP3A12 and CYP3A26 mRNAs in canine liver and intestine. Xenobiotica 2008; 38: 1305–1312.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement