DONOR LEUKEMIA FOLLOWING ALLOGENEIC BONE-MARROW TRANSPLANTATION

Although allogeneic bone marrow transplantation has been shown to be a highly effective treatment for acute and chronic leukemia, leukemic r elapse remains a significant problem. Leukemic relapse occurs In recip ient cells in the majority of cases, but the paucity of donor cell leu kemias may reflect the sensitivity of the investigative technique. We have developed a highly sensitive technique to identify the origin of all hematopoietic cells in the post transplant state which is based on PCR amplification of microsatellites, polymorphic tandem repetitive e lements. We have Identified donor leukemia(AML M5) following a sex mat ched BMT for severe aplastic anemia, verified a previously reported ca se of donor leukemia following BMT for chronic granulocytic leukemia a nd recently identified an acquired cytogenetic abnormality(del 11q23) in donor cells four years following an apparently successful BMT for A ML In all cases the donors have remained healthy. postulated mechanism s include transfer to the transplanted marrow of a dormant oncogene re siding in the DNA of either a virus, the chromosomes of degenerating i rradiation damaged host leukemic cells or in the marrow stroma which i s radioresistant and host in origin following BMT, Using sensitive tec hniques donor leukemia has been shown to be a more common event than w as previously thought and an understanding of its pathogenesis may all ow us to elucidate leukemogenic mechanisms in man.