Donor cell-derived acute myeloid leukemia developing 14 months after matched unrelated bone marrow transplantation for chronic myeloid leukemia

We report a patient with Ph-positive CML who developed a Ph-negative AMI, i n donor cells 14 months after BMT from an HLA-identical male unrelated dono r. The Ph translocation could not be detected by either conventional cytoge netics, FISH or RT-PCR analysis excluding relapse of CML in myeloid blast c risis. Chimerism studies were performed by variable number of tandem repeat s (VNTR) analysis. These revealed donor-type hematopoiesis in both unsepara ted mononuclear cells and CD34(+) selected blasts proving the leukemia to b e of donor origin. The patient received three cycles of polychemotherapy wi th mitoxantrone, topotecan and ara-c resulting in CR after the first treatm ent cycle and reconstitution with donor hematopoiesis. A second transplant from a female alternative matched unrelated donor was performed after condi tioning with fludarabine and 200 cGy TBI and was well tolerated. Nine month s after the second transplant the patient is at home and in CR. T cell chim erism was studied by sex chromosome analysis and revealed complete female d onor chimerism.