To condition or not to condition—That is the question: The evolution of nonmyeloablative conditions for transplantation

Abstract

In 1985, Eugene Cronkite published in Experimental Hematology data indicating that five consecutive “transfusions” of high numbers of marrow cells significantly increase the number of donor-derived cells detected by day 10 spleen colony forming assay, the most primitive hematopoietic cells detectable at that time, present in the host for as long as two months post transfusion (1). These data provided the first evidence that donor hematopoietic stem cells (HSC) may at least persist in vivo for some time in recipients that were transfused and not transplanted, i.e. not subjected to treatments that deplete their marrow niches of endogenous HSC. The limited technology available at the time prevented Dr. Cronkite to pursue this observation into the development of non-myeloablated transplantation procedures and his experiment as well as the term “bone marrow transfusion” have since long been forgotten. In recent years, the scientific need to clarify HSC functions in non-stressed hosts and the clinical need to develop transplantation procedures with levels of morbidity/mortality acceptable to cure inherited hematological disorders have inspired the search for non-myeloablative transplantation procedures including methods to “outcompete” endogenous host HSC such as those pioneered by Dr. Cronkite's experiments using high transfusion doses. This review will describe the technical progress since Dr. Cronkite's insightful work that has finally provided a path to the clinic.