Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 19, Issue 10, Pages 1474-1479Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2013.07.016
Keywords
Umbilical cord blood; Priming; Engraftment; Chimerism
Categories
Funding
- National Heart, Lung and Blood Institutes [1RC1HL099447-01]
- Production Assistance for Cellular Therapies (PACT) program [HHSN268201000008C]
- American Society of Blood and Marrow Transplantation Young Investigator Award
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Preclinical data showed that priming CD34(+) hematopoietic progenitor cells with complement fragment 3a (C3a) improved homing and engraftment. Thus, we hypothesized that priming of umbilical cord blood (UCB) hematopoietic progenitors with Oa would facilitate homing and could potentially be used to address the need for improved engraftment after UCB transplantation. We primed 1 of 2 UCB units for double UCB transplantation after nonmyeloablative conditioning. This design provided adequate safety and the potential to observe skewed long-term chimerism in favor of the C3a-primed unit as a surrogate measure of efficacy. Oa priming of 1 UCB unit did not result in infusional toxicity. Increased grades 1 to 3 hypertension were the only infusional adverse events observed in 9 (30%) patients. We observed no activation of inflammatory or coagulation pathways downstream of C3a. As tested, Oa priming did not impair engraftment, but did not skew chimerism toward the treated unit. As compared with historical controls, mortality and survival were not adversely affected. Thus, before any additional clinical studies, Oa priming to promote engraftment will require further preclinical optimization. (C) 2013 American Society for Blood and Marrow Transplantation.
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