Clonal hematopoiesis demonstrated by X-linked DNA polymorphisms after allogeneic bone marrow transplantation

We analyzed DNA from peripheral-blood and marrow cells from 12 recipients of allogeneic bone marrow transplants to determine whether monoclonal but otherwise normal hematopoiesis occurs in such patients. All patients were being treated for various forms of leukemia or lymphoma. In 10 patients, granulocytes isolated from peripheral-blood samples obtained 28 to 159 days after transplantation were polyclonal. In some, circulating T cells were isolated and also found to be polyclonal. In contrast, two patients had donor-derived monoclonal or oligoclonal hematopoiesis after transplantation. In one, DNA from circulating mononuclear cells obtained 29 days after transplantation revealed a monoclonal pattern on analysis of a restriction-fragment-length polymorphism in the phosphoglycerate kinase gene. In the other, analysis of a restriction-fragment-length polymorphism in the hypoxanthine phosphoribosyltransferase gene suggested the presence of a dominant clone in the granulocytes sampled 36 days after transplantation. When the latter patient was reassessed on day 267, the same clone of donor hematopoietic cells was still predominant and was found to include circulating T cells as well as granulocytes. We conclude that monoclonal hematopoiesis of donor origin may be observed in recipients of allogeneic bone marrow transplants, indicating that stem cells in normal adult human marrow are able to repopulate both lymphoid and myeloid compartments after transplantation.