CIRCULATING PROGENITORS FOLLOWING HIGH-DOSE SEQUENTIAL (HDS) CHEMOTHERAPY WITH G-CSF - SHORT INTERVALS BETWEEN DRUG COURSES SEVERELY IMPAIRPROGENITOR MOBILIZATION

Sequential administration of high-dose chemotherapy courses possibly a llows extensive in vivo purging before circulating progenitor collecti on for autograft. To evaluate whether progenitor cell mobilization was negatively affected by repeated high-dose chemotherapy courses, we st udied 23 lymphoma patients undergoing the HDS regimen. The scheme incl udes the sequential administration of cyclophosphamide (CY) given at 7 g/m(2) and etoposide (VP16) given at 2g/m(2), each followed by G-CSF (filgrastim) at 5 mu g/kg/day. Eleven patients received the standard H DS sequence, with a short interval between first and second myelotoxic courses of less than 45 days (median: 30 days); the remaining 12 pati ents received a modified HDS where the interval between first and seco nd high-dose course was protracted over 2 months (median: 70 days); in this latter group, 2 to 4 conventional debulking courses were deliver ed prior to HDS. In patients receiving the standard HDS, progenitor mo bilization following the first course was consistently high (median ci rculating CFU-GM/ml peak value: 29 022); however, significantly lower values were observed at the second course (median CFU-GM/ml peak value 3757, P = 0.002). Circulating BFU-E and CD34(+) cell values parallele d those of CFU-GM. No significant difference was observed in progenito r mobilization following either course in patients receiving HDS with extended interval (median circulating CFU-GM/ml peak value: 14363 vs 9 208, at first and second course respectively, P = 0.27). Eleven patien ts had their progenitor cells harvested following the second delayed c ourse and 2-4 leucaphereses allowed very satisfactory harvests in all of them (CFU-GM/kg ranging from 39-340 x 10(4)). The results indicate that mobilization is severely inhibited when the mobilizing treatment is delivered at a short interval after a previous one; however, adequa te mobilization is maintained even after repeated myelotoxic courses p rovided that a sufficient treatment-free interval is allowed before th e final mobilizing high-dose course.