Microchimerism and allogeneic transplantation:We need the proof in the pudding

摘要

Allogeneic stem cell transplantation (SCT) is the most effective treatment for leukemia and mediates its therapeutic effect to a large extent through immunologic effects, the so-called graft-vs-leukemia effects. Though highly effective it remains wrought with complications including opportunistic infections, graft vs. host disease as well as failure due to disease recurrence. Early animal experiments established that an HLA identical donor was a prerequisite for allogeneic SCT. But HLA-identical donors are elusive in societies where the number of siblings is decreasing and as scientists discover an ever larger number of HLA polymorphisms. Methods of transplantation that overcome HLA barriers are under intense investigation. HLA-mismatched Umbilicalcord blood (UCB) is increasingly used as a source of stem cells for HLA-mismatched allogeneic stem cell transplantation (SCT) and has unique features that could be manipulated to advance the field. UCB-SCT causes limited GVHD, compared with cells from adult donors and relapse rates of leukemia are relatively low after UCB SCT, suggesting that UCB-SCT mediates GVL through mechanisms that are separate from those that cause GVHD. In our recent article we review recent data on fetal immunology and UCB SCT that provide a plausible explanation for this clinical observation.