Residual adriamycin (AdR)-induced hematopoietic damage: a consideration for subsequent radiotherapy

The long-term effect of adriamycin (AdR) on the radiation response of hematopoietic marrow was studied at 16 weeks after treatment with a MTD (10 mg/kg) for the BDF1 mouse. The radiation response was monitored in both the "stem cell" (CFUs-8) and myeloid (CFU-gm, granulocyte, WBC) compartments, as well as the erythroid (BFUe, CFUe, HcT) compartments of the marrow for 14 days following a whole body dose (TBI) of 4.5 Gy X ray. At the time of irradiation, animal and spleen weight of AdR treated animals were reduced while HcT and WBC remained at control levels. At the same time the granulocyte and CFUs-8d compartments were depressed, while the BFUe compartment was expanded. The CFUe and CFU-gm compartments remained at control levels. For all marrow compartments, treatment with AdR 16 weeks prior to 4.5 Gy resulted in a radiation response deficit determined from the temporal recovery curves. The data suggest that manifestation of long-term AdR injury, at least through 16 weeks following treatment, is dependent on a subsequent stress of sufficient magnitude to enhance the proliferative activity associated with hematopoietic cell production and differentiation. A comparison is made between these observations and previously reported long-term drug-induced hematopoietic injury.