Cord-Blood Engraftment with Ex Vivo Mesenchymal-Cell Coculture
Top Cited Papers
- 13 December 2012
- journal article
- research article
- Published by Massachusetts Medical Society in New England Journal of Medicine
- Vol. 367 (24), 2305-2315
- https://doi.org/10.1056/nejmoa1207285
Abstract
Poor engraftment due to low cell doses restricts the usefulness of umbilical-cord-blood transplantation. We hypothesized that engraftment would be improved by transplanting cord blood that was expanded ex vivo with mesenchymal stromal cells. We studied engraftment results in 31 adults with hematologic cancers who received transplants of 2 cord-blood units, 1 of which contained cord blood that was expanded ex vivo in cocultures with allogeneic mesenchymal stromal cells. The results in these patients were compared with those in 80 historical controls who received 2 units of unmanipulated cord blood. Coculture with mesenchymal stromal cells led to an expansion of total nucleated cells by a median factor of 12.2 and of CD34+ cells by a median factor of 30.1. With transplantation of 1 unit each of expanded and unmanipulated cord blood, patients received a median of 8.34×107 total nucleated cells per kilogram of body weight and 1.81×106 CD34+ cells per kilogram — doses higher than in our previous transplantations of 2 units of unmanipulated cord blood. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 15 days in the recipients of expanded cord blood, as compared with 24 days in controls who received unmanipulated cord blood only (P<0.001); the median time to platelet engraftment was 42 days and 49 days, respectively (P=0.03). On day 26, the cumulative incidence of neutrophil engraftment was 88% with expansion versus 53% without expansion (P<0.001); on day 60, the cumulative incidence of platelet engraftment was 71% and 31%, respectively (P<0.001). Transplantation of cord-blood cells expanded with mesenchymal stromal cells appeared to be safe and effective. Expanded cord blood in combination with unmanipulated cord blood significantly improved engraftment, as compared with unmanipulated cord blood only. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00498316.)Keywords
This publication has 38 references indexed in Scilit:
- Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγnull miceExperimental Hematology, 2012
- Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord bloodBlood, 2010
- Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysisThe Lancet Oncology, 2010
- Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitutionNature Medicine, 2010
- Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferationBlood, 2009
- Single versus double unrelated umbilical cord blood units for allogeneic transplantation in adults with advanced haematological malignancies: a retrospective comparison of outcomesInternal Medicine Journal, 2008
- Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trialBone Marrow Transplantation, 2008
- Umbilical Cord Blood (UCB) Transplantation: An Alternative to the Use of Unrelated Volunteer Donors?Hematology-American Society Hematology Education Program, 2007
- Dynamic changes in cellular and microenvironmental composition can be controlled to elicit in vitro human hematopoietic stem cell expansionExperimental Hematology, 2005
- A Proportional Hazards Model for the Subdistribution of a Competing RiskJournal of the American Statistical Association, 1999