By Priv.-Doz. Dr. Hans-Peter Lohrmann, Priv.-Doz. Dr. Wolfgang Schreml (auth.)
Since cytotoxic medications have been first constructed, their destructive results on bone marrow have attracted substantial curiosity. We now comprehend that the bone marrow is an organ with swift cellphone renewal during which upkeep of the steady-state is dependent upon a excessive expense of phone construction, and that the bone marrow toxicity of cytotoxic brokers should be defined via the perturbation of such steady-state stipulations. Experimental researchers have analysed intimately the consequences of cytotoxic brokers upon outlined hematopoietic mobile populations to outline the mechanism of motion and the positioning in the cellphone cycle at which cytotoxic medicinal drugs exert their cytocidal motion. From such reports, a class of cytotoxic brokers in line with their motion upon cells in the course of diverse levels of the mobilephone cycle has been proposed [80-82]. Others have used the intense perturbation of the hematopoietic structures, attributable to software of unmarried excessive doses of cytotoxic brokers, to examine the styles of depletion and reconstitution of a few of the hematopoietic cubicles with a purpose to make clear the regulatory mechanisms which are liable for the delicately balanced phone construction of the hematopoietic phone renewal structures. loads of details at the constitution of the hematopoietic platforms has come from such experiences, and kinetic parameters of those platforms were outlined. To clinicians, the hematopoietic toxicity of antineoplastic brokers has been an undesired notwithstanding unavoidable part impression of just about all cytotoxic medicinal drugs brought into scientific practice.
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Additional resources for Cytotoxic Drugs and the Granulopoietic System
Nine days after cyclophosphamide, granulocytic regeneration had proceeded through most of the granulocytic compartments, with only the compartment of bands and segmented neutrophils awaiting full repletion (compartment sizes in percent of controls: myeloblasts 128; promyelocytes and myelocytes 265; metamyelocytes 211; bands plus segmented neutrophils 39). By day 12, the proliferating granulocytic compartment was slightly below control size; however, in the more mature granulocytic compartments, a rebound beyond normal values had occurred (metamyelocytes 263% of controls, bands plus segmented neutrophils 239% of controls).
In the study reported by Nakayama et al. ) was seen, but the time of the leukocyte nadir (days 11-13) and the duration of leukocyte depression (recovery by day 21) were identical at the different drug doses. After single high doses of cyclophosphamide, nadirs were usually reached between days 7 -12, and a return of peripheral blood granulocyte counts to pretreatment levels was usually completed after 3 weeks [31, 48, 49, 84, 85, 87, 324, 369, 518]. With doses of 800-1,200 mg/m 2 cyclophosphamide, moderate hematologic toxicity was noted WBC .
The updated results of this study are shown in Fig. 2. A sequential determination of the incidence of human CFU-C does not take into account that marrow cellularity simultaneously undergoes considerable changes, therefore, these data do not reflect changes in the size of the human CFU-C compartment of the bone marrow. A better quantification of the data is shown in Figs. 1 and 2: Based on the assumption (see page 14) that the cell concentration of standard marrow aspirates can be used as an indicator of marrow cellularity, we calculated the CFU-C concentration (CFU-C per ml aspirate), and considered this value as an approximate measure of the size of the CFU-C bone marrow compartment in man.
Cytotoxic Drugs and the Granulopoietic System by Priv.-Doz. Dr. Hans-Peter Lohrmann, Priv.-Doz. Dr. Wolfgang Schreml (auth.)