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History, Current Results, and Research in Marrow Transplantation

In 1949, Leon Jacobson and his colleagues, working here at the University of Chicago, showed that shielding the spleen allowed mice to recover from otherwise lethal irradiation [I]. Those studies were carried out in the course of studying the mechanisms of death from total body irradiation, and they are an example of laboratory studies carried out in animals which were, eventually, to have important human applications. Shortly thereafter, Lorenz, et al., showed that irradiation protection could be achieved by an infusion of syngeneic marrow [2]. In 1955, Main and Prehn showed that mice protected with an infusion of allogeneic marrow would subsequently accept permanently a skin graft from the marrow donor [3]. Ford, et al., used cytogenetic techniques to show that the irradiation protection effect was due to the transfer and survival of living donor hematopoietic cells [4]. In 1956, Barnes, et al., reported the treatment of leukemia in mice by irradiation and marrow transplantation [5]. These studies marked the beginning of the field of marrow transplantation. The potential application of supralethal chemo-irradiation and marrow grafting for therapy of leukemia and other diseases of the marrow was immediately apparent. Dr. Joseph Ferrebee and I and our colleagues in Cooperstown, NY, began a human marrow grafting program in 1955. Our first publication in 1957 demonstrated that allogeneic marrow grafting in our species would be difficult [6]. We did show that large quantities of marrow could be safely infused intravenously, but only one patient showed transient engraftment. In that paper we estimated the approximate dose of marrow cells needed, and we warned about the dangers of a graft-versus-host reaction. Subsequently, two