Researchers from Spain have reported that the addition of highly purified CD34+ stem cells from a third party donor improves neutrophil and platelet recovery in adults receiving a single unrelated umbilical cord blood transplant following a reduced intensity but still myeloablative treatment regimen for leukemia. The results of this study were presented at the Third Annual International Umbilical Cord Blood Transplantation Symposium in Los Angeles, June 3-4, 2005.

Umbilical cord blood is an acceptable source of stem cells for patients who lack a suitable unrelated stem cell donor. There is convincing evidence that the outcomes of children with leukemia receiving unrelated cord blood transplants are similar to those achieved with standard unrelated donor transplants. However, in both children and adults the rate of recovery of marrow function is significantly prolonged compared to unrelated peripheral blood stem cell or bone marrow transplantation. Attempts to accelerate recovery of neutrophils and platelets include the infusion of in-vitro expanded cord blood stem cells and the infusion of two rather than one unrelated cord blood units.

The current study describes a third approach; the infusion of T-cell depleted CD34+ stem cells obtained from the peripheral blood of mismatched relatives. These researchers evaluated this approach in 28 patients with advanced leukemia (half with advanced acute lymphoblastic leukemia) who were an average age of 30 years and an average weight of 67 kilograms with the highest weight being 87 kilograms. The most commonly used treatment regimen was the combination of cyclophosphamide, total body irradiation and anti-thymocyte globulin. Donors of peripheral blood stem cells were haploidentical relatives (n=20) or donors which shared no haplotypes (n=4). In four instances, the mother was the donor.

The median time to neutrophil recovery was 10 days and the median day to platelet recovery was 22 days. The median time to full donor chimerism was 54 days. These recovery times are much more rapid than previously observed with a single umbilical cord blood unit. However, stem cells from the mother were not effective in improving the rate of neutrophil and platelet recovery, presumably because of in-utero sensitization to the mothers’ antigens. When patients receiving maternal stem cells were excluded from analysis, engraftment was even faster in the remaining patients. Treatment related mortality was 28% with two toxic deaths, one graft failure, to graft-versus host disease, and three from opportunistic infection. Only 3 of 27 patients relapsed. Overall survival at 4 years was 67%. When patients older than age 40 years and recipients of maternal stem cells were excluded overall survival was 86%.

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Reference:

Fernandez, MN. Unrelated single cord blood transplants supported by co-infusion of a low number of mobilized peripheral blood highly purified CD34+ cells from a third party donor after low toxicity myeloablative conditioning. Proceedings from the Third Annual International Umbilical Cord Blood Transplantation Symposium. Los Angeles, Calif. 2005;30.

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