A 22-year-old man with chronic myeloid leukemia (CML) received fractionated total body irradiation (TBI) (1440cGy) and etoposide (60 mg/kg) followed by infusion of 10 x 10(6) /kg CD34+ selected stem cells from his mother. Donor and recipient were 50% matched at the HLA-A and -B loci and 100% at HLA-DR. Mixed lymphocyte culture reaction was negative. Post-stem cell transplant (SCT) immunosuppression consisted of antithymocyte globulin, cyclosporine, and prednisone, and was discontinued after 7 months. The donor graft was rejected 2 years post-SCT. At 7 years post-SCT, he is clinically well with normal blood counts and no evidence of CML or myelodysplasia despite the presence over 6 years of multiple clones with balanced translocations and deletions in host bone marrow cells. The emergence of clonal hematopoiesis may provide insights into therapy-related leukemogenesis.