Relapse after allogeneic BMT for chronic myeloid leukemia (CML) may be sustained by a small number of leukemic 'stem cells': a hypothesis

We performed cytogenetic analysis on fresh bone marrow cells and on progeni tor cell colonies in a patient who relapsed after allogeneic BMT for CML an d was subsequently treated with donor lymphocyte infusions (DLI), Two Phila delphia-positive clones were identified at relapse. One clone displayed an additional chromosomal abnormality most likely induced by radio-chemotherap y and therefore arising in a single cell, This cell displays the characteri stics of a stem cell, since it was able to support 20% of Ph-positive hemop oiesis for 5 months. If the progeny of a single Ph-positive stem cell accou nt for 20% of hemopoiesis, a very low number of leukemic stem cells may sus tain relapse after allogeneic BMT, This is in keeping with two observations : (I) at relapse, long-term culture initiating cells (LTC-IC) were all dono r-derived and Ph-negative; (2) on average, the pace of the disease is very slow after relapse following allogeneic-BMT, Therefore, we hypothesize that a small number of leukemic stem cells may be involved in the initial event s of relapse following BMT for CML.