The effects of cancer chemotherapeutic agents on normal hematopoietic precursor cells: a review

Abstract

The effects of antineoplastic agents, singly or in combination, on normal hematopoietic precursor cells have been reviewed. Following a description of the assays used (e.g., spleen colony, in vitro colony, repopulating ability), the dose response and/or time response for each drug are presented by species and by assay as available. The schedule of drug administration, the time of the assay, and the proliferative state of the target population are the most important determinants. Alkylating agents, antitumor antibiotics, and 5-fluorouracil have exponential dose survival curves. "Phase-specific" agents such as antimetabolites, Vinca alkaloids, and ribonucleotide reductase inhibitors have plateaus in their dose survival curves, although the level of this plateau is different for different agents. Most drugs are more effective against rapidly proliferating cells although busulfan is less effective. Direct interspecies comparisons are possible with some of the clonogenic assays, which may allow prediction of the magnitude of human hematological toxicity for new agents or combinations.