INHIBITION OF CFU-C GROWTH BY VP-16 CONTAINING PLASMA SAMPLES OBTAINED FROM PATIENTS AFTER CONDITIONING THERAPY FOR BONE-MARROW TRANSPLANTATION

The introduction of VP-16 into high-dose therapy regimens used for con ditioning before BMT or PBSCT has resulted in higher remission rates a nd prolonged disease-free survival, even in high risk patients. VP-16 levels have been measured in plasma at the time of transplantation. Th e question is, is there a biological activity that corresponds with th e risk of delayed engraftment or graft failure? We investigated the in hibitory effects of plasma samples obtained from patients under high-d ose VP-16 therapy on the growth of human bone marrow progenitor cells. Bone marrow cells from healthy donors were exposed to the plasma samp les and seeded into methylcellulose-culture (CFU-C-assay). We found a dose dependent CFU-C inhibition related to VP-16 plasma levels at the time of transplantation (k = 0.769, P < 0.01). There were signs of a c orrelation between CFU-C growth inhibition at the time of BMT and haem atological recovery (k = 0.656, P < 0.05) between CFU-C inhibition and the time until leucocytes reached 0.2 x 10(9)/1. Patients with CFU-C growth inhibition at the time of BMT may show delayed engraftment of l eucocytes and that there might be a correlation with VP-16 levels, but further investigation is necessary to determine the significance of t he latter thesis and if VP-16 plasma levels could lead to failure of e ngraftment. We recommend a minimum time interval between VP-16 infusio n and graft transplantation of 72 h.