RESULTS OF MDR-1 VECTOR MODIFICATION TRIAL INDICATE THAT GRANULOCYTE MACROPHAGE COLONY-FORMING UNIT CELLS DO NOT CONTRIBUTE TO POSTTRANSPLANT HEMATOPOIETIC RECOVERY FOLLOWING INTENSIVE SYSTEMIC THERAPY/

To formally test the hypothesis that the granulocyte/macraphage colony -forming unit (GM-CFU) cells can contribute to early hematopoietic rec onstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is speci fic for the multidrug resistance-1 (MDR-1) vector, and by a quantitati ve GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the product s of two different transduction protocols: ''suspension transduction'' and ''stromal growth factor transduction.'' However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector po sttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the c ells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assa y (a difference that is significant at the P = 0.0065 level by the Fis her exact test), These data suggest that only very small subsets of th e GM-CFU fraction of myeloid cells, if any, contribute to the repopula tion of the hematopoietic tissues that occurs following intensive syst emic therapy and transplantation of autologous hematopoietic cells.