POLYCLONAL RECONSTITUTION OF HUMAN MARROW AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Abstract

Clonal dominance suggestive of reconstitution of marrow from small numbers of pluripotent hematopoietic stem cells has been noted in different experimental and clinical situations. Recipients of human allogeneic marrow transplants have not been previously studied to determine if clonal dominance occurs in this clinical setting. Clonal analysis of 20 allogeneic marrow transplant recipients was performed on DNA from peripheral blood neutrophils using restriction fragment length polymorphisms on the X chromosome. Similar studies were performed on 16 of the donors. To analyze the results further, recipients were paired with their respective donors. There was no evidence of shifts in cell populations contributing to the X chromosome inactivation patterns in recipient marrow grafts when compared with their respective donors. A mathematical model based on binomial statistics was adapted to estimate the numbers of recontituting pluripotent hematopoietic stem cells. There was no evidence of clonal dominance suggestive of oligoclonal reconstitution in marrow grafts after allogeneic marrow transplantation. This does not preclude the possibility of oligoclonal reconstitution in other marrow transplant settings such as autologous transplantation.