RETROVIRAL GENE-TRANSFER IN AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR ADULT ACUTE-LEUKEMIA

To evaluate whether marrow contributes to relapse after autologous bon e marrow transplantation (AuBMT) for acute leukemia, transplanted marr ow was marked with the G1N retroviral vector (Genetic Therapy Inc.) co ntaining the neomycin phosphotransferase gene (neo), Between April 199 2 and August 1993, 4 patients were transplanted for acute myeloid leuk emia (AML) in second complete remission (CR) and 1 patient for acute l ymphoid leukemia in first CR, An average of 12.4% (range 5-19%) of tra nsplanted marrow mononuclear cells were exposed to G1N vector for 4 hr , In the vector-treated portion of the marrow, 4.9% of GM-CFU and 3.6% of erythroid burst-forming units (BFU-E) were resistant to G418 in vi tro, In the 5 patients, the polymerase chain reaction (PCR) detected t he neo sequence on only two occasions after AuBMT, Of 4 patients survi ving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR, Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT, The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse, O ur results indicate vector-transduced autologous bone marrow from heav ily pretreated adults with acute leukemia mark with low efficiency, al though vector sequences have been detected in bone marrow and peripher al blood up to 1 year after transplant, Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected.