title: Comparison of the Sysmex XT-2000iV and microscopic bone marrow differential counts in Wistar rats treated with cyclophosphamide, erythropoietin, or serial phlebotomy.
abstract: BACKGROUND
  In a previous study, it was demonstrated that bone marrow analysis using the Sysmex XT-2000iV hematology analyzer produced differential counts in untreated rats that were comparable to microscopic differential counts.
  
  
  OBJECTIVE
  The aim of this study was to modulate hematopoiesis in rats in vivo either through pharmacologic treatment or serial phlebotomy, and to determine whether the Sysmex XT-2000iV could accurately analyze bone marrow quantitative changes when compared with results obtained by microscopy.
  
  
  METHODS
  Rats were treated once with 0, 5, 20, and 40 mg/kg cyclophosphamide (CP), 0, 50, 100 IU/kg erythropoietin (EPO) on 4 consecutive days, or serial phlebotomy of 1-2 mL of blood for 4 days. Modulation of hematopoietic populations in bone marrow was evaluated using the Sysmex XT-2000iV hematology analyzer, and compared with microscopic differential counts.
  
  
  RESULTS
  Correlation coefficients between M:E ratios determined by Sysmex and the microscopic method were 0.94, 0.96, and 0.98 for CP, EPO, or serial phlebotomy treatments, respectively. Mean concordance correlation coefficients for M:E demonstrated method agreement of 0.63, 0.92, and 0.85 for the 3 treatments. Quantitative automated and microscopic bone marrow differential counts were within the expected 95% confidence intervals for CP, EPO or serial phlebotomy.
  
  
  CONCLUSIONS
  The Sysmex XT-2000iV provides quantitative bone marrow differential counts of bone marrow cell series in rats with treatment-induced changes which are comparable to microscopic differential counts. Reliable automatic bone marrow differential counting allows increased throughput, sensitivity, reproducibility, and enhanced interpretation of bone marrow evaluation in rodent preclinical studies.
authors.affiliation: Pfizer Worldwide Research and Development, Drug Safety Research and Development, Groton, CT, USA.
authors.forename: Kay A
authors.initials: KA
authors.lastname: Criswell
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Bock
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Wildeboer
authors.forename: Kjell
authors.initials: K
authors.lastname: Johnson
authors.forename: Richard P
authors.initials: RP
authors.lastname: Giovanelli
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002452:Cell Count / Q000662:veterinary; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000662:veterinary; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D018962:Phlebotomy / Q000662:veterinary; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D007166:Immunosuppressive Agents; D004921:Erythropoietin; D003520:Cyclophosphamide
keywords: Cytology; flow cytometry; hematotoxicity; preclinical safety