Effective ex vivo purging techniques can decrease the likelihood of infusing bone marrow contaminated with leukemic cells during
autologous transplantation. In preliminary studies,
OL(1)p53, a 20-mer phosphorothioate
oligonucleotide directed against p53
mRNA, decreased the number of
acute myelogenous leukemia (AML) cells in vitro, suggesting a possible role for
OL(1)p53 in
purging bone marrow harvests of
leukemia cells. To demonstrate that
OL(1)p53 was nontoxic to hematopoietic progenitor cells, normal bone marrow cells were incubated with 10 microM
OL(1)p53 for 36 h, and hematopoietic progenitor cell survival was determined by in vitro colony assays.
OL(1)p53 had no toxic effect on the growth of either myeloid (CFU-GM) or erythroid (BFU-E) progenitor cells.
OL(1)p53 was then used to ex vivo purge bone marrow harvests from nine patients with either AML or
myelodysplastic syndrome (MDS). Bone marrow cells were incubated with 10 microM
OL(1)p53 for 36 h before
transplantation. The median times posttransplantation for the patient to recover an absolute neutrophil count greater than 0.5 x 10(9)/L and a
platelet transfusion independence were 30 days and 56 days, respectively. Incubation of bone marrow cells with
OL(1)p53 had no detrimental effect on the growth of hematopoietic progenitor cells, and
transplantation of autologous bone marrow cells treated with the phosphorothioate
oligonucleotide,
OL(1)p53, resulted in successful recovery of circulating neutrophils following high-dose
therapy in patients with AML or MDS. The data show that
OL(1)p53 can be used safely to purge autologous bone marrow harvests from patients with
leukemia.