In vivo leukemic transformation: cytogenetic evidence of in vivo leukemic transformation of engrafted marrow cells

A 4-year-old girl with acute myeloblastic leukemia was treated with 50 mg/kg cyclophosphamide daily for 4 days before being given 1.7 X 10(8) bone marrow cells/kg from her HL-A identical, MLC nonreactive, cytogenetically normal brother. The patient died 92 weeks after the marrow graft. Postmortem examination showed increased myeloblasts and promyelocytes. Cytogenetic studies before transplantation showed that all sex determination metaphases had an XX pattern, and 41% of the hyperdiploid metaphases had an additional 19-20(F) chromosome. At autopsy all hyperdiploid metaphases with XY pattern and 43% of the hyperdiploid metaphases with an XX pattern had an additional F chromosome. Occasional metaphases with 47, XX, + F or 47, XY, + F were seen during the follow-up studies. These findings indicated that an acute leukemia had developed in the XY cell line of this artifically induced sex chimeric child. This suggests that a leukemic stimulus other than that proposed to be induced by total-body irradiation existed in this patient and transformed the engrafted cells.