Blood or marrow stem cells?

In the beginning, there was bone marrow. A quarter of a century ago, the concept was simple: a patient had a bad bone marrow (eg, aplastic anemia) or a marrow destroyed by therapy (acute leukemia), and one substituted a healthy, allogeneic marrow. Gradually it became possible to distinguish and then manipulate marrow cellular subsets. For instance, T lymphocytes were found to be important in acute graft-versus-host disease (AGVHD), and strategies evolved to reduce their numbers in the marrow inoculum. The results were mixed, with graft failure and increased relapse replacing the problem of AGVHD. Once the hematopoietic progenitor cells were recognizable, it was seen that placental blood had large numbers of such and also that the T-lymphocyte population appeared naive: perhaps one could get engraftment with less AGVHD. Again, the results were mixed: less AGVHD, but slower engraftment. More recently, allogeneic cytokine-mobilized peripheral blood stem cells (PBSCs) have come under study. On the one hand, large numbers of CD34⁺ cells can be collected, but there were concerns about an increased risk of chronic graft-versus-host disease (CGHVD). PBSC products contain large numbers of T lymphocytes, and previous experience using noncytokine mobilized peripheral blood cells clearly showed a higher risk of CGVHD (although with more reliable engraftment in aplastic anemia patients).

The study in this issue (page 1525) reports a multicenter, randomized trial comparing marrow to cytokine-moblized PBSCs. The results are similar to those previously published by the Seattle group: the PBSC group had faster engraftment (4 days for neutrophils, 6 days for platelets) and slightly better survival. The current study shows that most of the survival advantage is seen in the poor-risk patients, as opposed to the good-risk ones: this again is similar to what Seattle showed. The reason for the advantage in the poor-risk patients is not clear: 4 days faster engraftment would seem to be advantageous, but it might be useful to also study whether there are relevant differences in the cellular components in the respective products which could explain such an advantage, such as larger numbers of cells to suppress incipient infections or to speed healing of previous endothelial damage.