In a prevalidation study, a Standard Operating Procedure (SOP) for human and mouse in vitro tests was developed, for evaluating the potential haematotoxicity of xenobiotics in terms of their direct, adverse effects on the myeloid colony-forming unit (CFU-GM). Based on the adjustment of the mouse-derived maximum tolerated dose (MTD), a prediction model was set up to calculate the human MTD, and an international blind trial was designed to apply this model to the clinical neutropenia of 23 drugs including 17 antineoplastics. The model correctly predicted the human MTD for 20 drugs out of the 23 (87%). This high percentage of predictivity, and the reproducibility of the SOP testing, confirmed the scientific validation of this model, and suggested promising applications for developing and validating other in vitro methods for use in haematotoxicology.
BallsM., BlaauboerB.J., FentemJ.H., BrunerL., CombesR.D., EkwallB., FielderR.J., GuillouzoA., LewisR.W., LovellD.P., ReinhardtC.A., RepettoG., SladowskiD., SpielmannH., & ZuccoF. (1995). Practical aspects of the validation of toxicity test procedures. The report and recommendations of ECVAM workshop 5. ATLA23, 129–147.
2.
CurrenR.D., SoutheeJ.A., SpielmannH., LiebschM., FentemJ.H., & BallsM. (1995). The role of prevalidation and validation in the development, validation and acceptance of alternative methods. ECVAM Prevalidation Task Force Report 1. ATLA23, 409–470.
3.
DuD.L., VolpeD.A., GrieshaberC.K., & MurphyM.J.Jr. (1990). Effects of L-phenylalanine mustard and L-buthionine sulfoximine on murine and human haematopoietic cells in vitro.Cancer Research50, 4038–4043.
4.
DeldarA., & StevensC.E. (1993). Development and application of in vitro models of haematopoiesis to drug development. Toxicologic Pathology21, 231–240
5.
GribaldoL., BuerenJ., DeldarA., OklandP., MeredithC., MonetaD., MosessoP., ParchmentR., Parent-MassinD., PessinaA., San RomanJ., & SchoetersG. (1996). The use of in vitro systems for evaluating haematotoxicity. ATLA24, 211–231
6.
MetcalfD. (1984). The basic biology of haematopoiesis. In The Haematopoietic Colony Stimulating Factors (ed. MetcalfD.), pp. 1–26. Amsterdam, The Netherlands: Elsevier.
7.
GrandeT., & BuerenJ.A. (1995). Analysis of the haematopoiesis in mice irradiated with 500mGy of X-rays at different stages of development. Radiation Research143, 327–333
8.
BruceW.R., MeekerB.E., & ValerioteF.A. (1966). Comparison of the sensitivity of normal haematopoietic and transplanted lymphoma colony forming cells to chemotherapeutic agents administered in vivo.Journal of the National Cancer Institute37, 233–245
9.
ParchmentR.E., GordonM., GrieshaberC.K., SessaC., VolpeD., & GhielminiM. (1998). Predicting haematological toxicity (myelosuppression) of cytotoxic drug therapy from in vitro tests. Annals of Oncology9, 357–364.
10.
ParchmentR.E. (2000). Oncology clinical trials and in vitro prediction models for xenobiotic toxicology. Developments in Animal Veterinary Science31, 693–708.
11.
BradleyT.R., & MetcalfD. (1966). The growth of mouse bone marrow cells in vitro.Australian Journal of Experimental Biology and Medical Science44, 287–300
12.
PessinaA., AlbellaB., BuerenJ., BrantomP., CasatiS., GribaldoL., CroeraC., GagliardiG., FotiP., ParchmentR., Parent-MassinD., SibirilY., SchoetersG., & Van Den HeuvelR. (2001). Prevalidation of a model for predicting acute neutropenia by colony forming unit granulocyte/ macrophage (CFU-GM) assay. Toxicology in Vitro15, 729–740.
13.
ParchmentR.E., HuangM., & Erickson-MillerC.L. (1993). Roles for in vitro myelotoxicity tests in preclinical drug development and clinical trial planning. Toxicologic Pathology21, 241–250.
14.
ParchmentR.E., VolpeD.A., LoRussoP.M., Erickson-MillerC.L., HuangM., MurphyM.J.Jr., & GrieshaberC.K. (1994). An in vivo–in vitro correlation of the myelotoxicity of 9-methoxypyrazoloacri-dine (PZA, NSC-366140, PD115934) to myeloid and erythroid haematopoietic progenitors from human, murine and canine marrow. Journal of the NationaI Cancer Institute86, 273–280.
15.
VolpeD.A., TomaszewskiJ.E., ParchmentR.E., GargA., FloraK.P., MurphyM.J.Jr., & GrieshaberC.K. (1996). Myelotoxic effects of the bifunctional alkylating agent bizelesin to human, canine, and murine myeloid progenitor cells. Cancer Chemotherapy and Pharmacology39, 143–149.
16.
Erickson-MillerC.L., MayR., TomaszewskiJ., OsbornB., MurphyM.J.Jr., PageJ.G., & ParchmentR.E. (1997). Differential toxicity of camptothecin, topotecan and 9-aminocamptothecin to human, canine, and murine myeloid progenitors (CFU-GM) in vitro.Cancer Chemotherapy and Pharmacology39, 467–472.
