Effects of cyclophosphamide and of busulfan on spleen colony-forming units and on hematopoietic stroma

Abstract

The effects of cyclophosphamide (CY) and busulfan (BU) on the hematopoietic stromal function (HS-P) of mouse marrow were evaluated. Stromal function of femoral marrow was assessed by implanting the test femur s.c. into an isogeneic host and determining the number of CFU-S in the implant 6 weeks later. Since the CFU-S have been shown previously to be primarily of host origin, this presumably measures the abilit- of donor hematopoietic sites to harbor host CFU-S. After injection of CY, the number of CFU-S in the marrow fell but recovered to normal within 6 weeks. The HS-P function fell to half-normal after 10 mg of CY and did not regenerate detectably in 6 weeks. On the other hand, 2 mg of BU i.p. caused a lesser initial decline in the number of CFU-S, but recovery was still incomplete after 6 weeks. BU given p.o. had a more marked effect on CFU-S and caused a significant decline in the HS-P function. Doses of CY (5 mg/dose) given intermittently appear to cause cumulative damage to HS-P function. HS-P function did not, in any experiment, recover significantly in the 6 weeks following the last dose of CY. This result suggests that large doses of the alkylating agent CY causes prolonged and perhaps permanent HS-P damage. This damage to the HS-P is cumulative when the CY is given at weekly intervals. Despite lack of HS-P recovery, CFU-S regenerate rapidly after CY therapy is stopped. On the other hand, BU also causes damage to the HS-P. However, even when BU is given at a dosage that does not significantly affect the HS-P, CFU-S recovery is delayed, suggesting that BU affects the CFU-S in a manner that differs qualitatively from that of CY.