Progress with unrelated cord blood transplants in adults

Joanne Kurtzberg

In the 1980s, the idea that umbilical cord blood (UCB) contained sufficient hematopoietic stem cells to rescue myeloablated bone marrow was disregarded by most marrow transplanters. In 1989, when Gluckman and colleagues reported the successful transplantation into a 6-year-old boy with Fanconi anemia of HLA-matched cord blood from his baby sister (Gluckman et al, N Engl J Med. 1989;321:1174-1178), many thought that the substitute of this unique stem cell source would only have utility in children. This perception was reinforced in 1996 when the results of the first 25 unrelated, partially HLA-mismatched transplantations performed between 1993 and 1995, with units from the public bank established by Dr Pablo Rubinstein, demonstrated a 48% event-free survival, again in children (Kurtzberg et al, N Engl J Med. 1996;335: 157-166). In these early studies, cord blood was shown to cause less acute and chronic graft-versus-host disease than did better-matched adult stem cells, stimulating the use of mismatched unrelated cord blood transplantation in patients lacking matched donors. In follow-up, the first UCB transplant recipient, as well as 11 of the 12 survivors of the first 25 unrelated transplantations, originally reported in 1996, are currently in good health with 100% donor chimerism.

Reports over the next 5 years from single institutions and various registries observed that the cell dose delivered by the cord blood unit influenced engraftment and overall survival. Given that adults are larger than children, there was limited enthusiasm for use of cord blood in adults and the limited retrospective trials performed in the United States demonstrated inferior outcomes, due in large part to selection of patients with end-stage disease receiving low (fewer than 2 × 107 cells/kg) cord blood cell dosing (Laughlin et al, N Engl J Med. 1002;344:1815-1822). The study by Ooi and colleagues in this issue (page 4711) provides the first encouraging results in adults receiving transplants of unrelated cord blood.

What is different? Cell dosing! It appears that cord blood dosing approaches the threshold necessary for engraftment. When dosed with adequate numbers of cells (in this report a median of 2.43 × 107 cells/kg), a group of very high–risk patients can demonstrate superior survivals. The authors should be congratulated for their perseverance in testing and contributing to our understanding of this promising stem cell source.