Cryopreservation of autologous marrow grafts in acute leukemia: survival of in vivo clonogenic leukemic cells and normal hemopoietic stem cells.

The survival of pluripotent hemopoietic stem cells and in vivo clonogenic leukemic cells after cryopreservation was determined in a rat model for human acute myelocytic leukemia (BNML). These stem cell populations can be selectively quantified with modified spleen colony assays (day 8 and day 12 CFU-S; LCFU-S). It appeared that the most primitive rat hemopoietic stem cell (day 12 CFU-S) was significantly less vulnerable to the freezing and thawing procedure as compared with the clonogenic leukemic cell (30% and 1.4% survival, respectively; p = 0.0026). Survival of the day 8 CFU-S population fell between those percentages (8.6%). In view of autologous bone marrow transplantation (ABMT), an attempt was made to extrapolate these and previously reported BNML rat data to man. Taking into account that a) only 1% of the clonogenic leukemic cells survive cryopreservation; b) the fraction of clonogenic leukemic cells in man is approximately 0.001; c) leukemic cells reinfused with the autologous marrow graft may lodge at sites unfavourable for growth; and d) supralethal high-dose chemoradiotherapy significantly hampers the regrowth of leukemia, it becomes rather unlikely that leukemic cells in the autologous marrow graft significantly contribute to a leukemia relapse after ABMT. Therefore, residual leukemia in the host surviving high-dose chemoradiotherapy is the most crucial factor as regards the final outcome of ABMT in acute leukemia.