Culture purging in leukemia: past, present, and future

Over the past 5 years we have been evaluating the feasibility of using cultured marrow autografts to allow patients with chronic myeloid leukemia (CML) to receive intensive, potentially curative therapy. The rationale for this approach is based on two important findings. The first is that leukemic stem cells (operationally defined as Ph-positive long-term culture-initiating cells, or LTC-IC) are present in the marrow of many CML patients at relatively low levels by comparison to co-existing normal stem cells (i.e., Ph-negative LTC-IC). The second finding is that leukemic LTC-IC are selectively "purged" following their incubation in vitro for 10 days under LTC conditions. As a result, cultured CML marrow preparations show, on average, a 300-fold selection in favour of normal LTC-IC. However, there is considerable variation in the initial normal and leukemic LTC-IC content of marrow samples from different CML patients. Thus in only approximately one third of cases does the number of leukemic LTC-IC in the marrow decrease to undetectable levels within the first 10 days of culture with the number of co-existing normal LTC-IC remaining at or above 1/50th of the average value for normal marrow. We have now transplanted 22 such CML patients with 10 day cultured marrow autografts following their treatment with myeloablative therapy. Fifteen of these patients were in first chronic phase and 7 had more advanced disease.(ABSTRACT TRUNCATED AT 250 WORDS)