Long-term marrow cultures: in vitro purging of leukaemic cells

After induction and consolidation chemotherapy, patients with acute myeloid leukaemia (AML) usually achieve clinical remission. However, leukaemic cells, although not readily apparent, persist in most patients since the remissions cannot be sustained without further cytoreductive measures. To eradicate residual disease after induction chemotherapy, various treatment options (particularly allogeneic bone marrow transplantation) have been used. Autologous bone marrow transplantation (ABMT) can also lead to long-term survival, presumably due to the eradication or control of residual disease, but this occurs in only about 50% of cases transplanted. Relapse in the other patients occurs as a consequence of leukaemic cells surviving the conditioning regimen and/or the infusion of leukaemic cells present in the autografted bone marrow. In attempts to decrease the relapse rates after ABMT, chemical or immunological methods for in vitro purging of the harvested bone marrow cells to remove residual leukaemia have been used: the effectiveness of these procedures is unproven. This chapter describes the biology of long-term bone marrow cultures (LTBMC). How the biological differences between normal and leukaemic cells in LTBMC can be exploited to encourage the growth of normal haemopoietic cells at the expense of leukaemic cells, and how these cultured cells can be used in ABMT are discussed. The survival of patients after LTBMC/ABMT and the low relapse rate indicate that this is a useful therapeutic approach in the treatment of patients with leukaemia.