Effects of Cis-diamminedichloroplatinum (II) on hematopoietic stem cells in mice

Bone marrow cell responses to therapeutic doses of cis-diamminedichloroplatinum (II) (Cis-Pt) were evaluated in female C57B1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFUS) after treatment. Although limitation on the dosage of Cis-Pt is generally considered to be determined by renal toxicity, methods to increase the effective use of the drug such as hydration and diuresis, alteration of time-dose schedules and combination of Cis-Pt with other drugs and radiation, warrant studies on effects of the drug on other normal tissues such as bone marrow. Cis-Pt given on a time-dose schedule that is therapeutic for mice and, in general, is equivalent to regimens recommended for clinical use, was found to be myelosuppressive. The myelosuppression was dose related in that a total dose of 16 mg/kg (2 doses at weekly interval) reduced the number of CFUS/femur to 16% of the control value, 24 mg/kg (4 doses at weekly intervals) reduced the CFUS fraction to 10-14% of the value for controls and 32 mg/kg (4 doses at weekly intervals) reduced the fraction of CFUs to 6-7% of the control value. A quantitative extrapolation of these effects to man cannot be made, however, the data indicate that myelosuppression could become a significant factor as increased doses of Cis-Pt are used clinically.