Sensitivity of human CFU-GM to mafosfamide: analysis of the factors affecting individual variations

A study of CFU-GM sensitivity to mafosfamide was carried out in 67 candidates for ABMT. A lethal dose 95 (LD95) was calculated from the dose-response curve. Despite standardized treatment conditions of marrow buffy-coat cells, LD95 values that were normally distributed (median 100 micrograms/ml; mean +/- SEM 95.6 +/- 4.0 micrograms/ml) varied considerably from patient to patient (range 30-160 micrograms/ml). Three independent factors appeared to confer greater sensitivity of CFU-GM: low patient age, low CFU-GM rate in treated cells and prolonged delay of CFU-GM sensitivity test from last chemotherapy course. In contrast, sex, pathology, disease status, number of previous chemotherapies and use of CY before the test did not influence CFU-GM sensitivity. Forty-six patients were autografted with mafosfamide-treated marrows according to their LD95. The mean percentage of CFU-GM effectively recovered after graft purging was 3.96 +/- 2.09%. All patients engrafted well and their peripheral blood cell recoveries were correlated with graft CFU-GM content evaluated before purging but not after purging or after freezing. In multivariate analysis, this parameter remained the only factor predicting hematopoietic recovery among other patient variables such as sex, age, pathology, disease status, previous chemotherapies or TBI in conditioning regimens. In a subgroup of 39 patients with lymphoid malignancies compared with 25 patients autografted for non-Hodgkin's lymphomas with unpurged marrows, the delay in days (medians) was similar for leukocytes > 1 x 10(9)/l (19 vs 17 days) and for neutrophils > 0.5 x 10(9)/l (18 vs 17 days) while it was longer for platelets > 50 x 10(9)/l (34 vs 128 days).(ABSTRACT TRUNCATED AT 250 WORDS)