Author Interviews, General Medicine, Leukemia, NEJM, Transplantation / 03.11.2014
Hematologic Cancers: Umbilical Cord Transplantation – One vs Two Units
MedicalResearch.com Interview with:
John E. Wagner, M.D.
Principal Investigator
Professor Director, Division of Blood and Marrow Transplantation Department of Pediatrics McKnight Presidential Endowed Chair Hageboeck Family / Children's Cancer Research Fund Endowed Chair University of Minnesota Minneapolis, MN 55455
Medical Research: What is the background for this study? What are the main findings?
Dr. Wagner: Earlier studies of umbilical cord blood transplantation (UCB) in children with hematological malignancies demonstrated a survival rate of approximately 50%. While single UCB transplant was very effective despite HLA mismatch, few adults had access to umbilical cord blood as a treatment option due to the cell dose requirement of 2. 5 x 10^6 nucleated cells per kilogram recipient body weight. For this reason, at the University of Minnesota we explored the co-transplantation of two partially HLA matched umbilical cord blood units in adults as a straightforward strategy to achieving the cell dose requirement. Early results were remarkable with survival rates higher than that observed in children. This in turn led to the design of the BMT CTN 0501 study, a randomized trial comparing single versus double umbilical cord blood transplantation in children aged 2-21 years with hematological malignancies. All patients received a uniform conditioning regimen of fludarabine, cyclophosphamide and total body irradiation and GVHD prophylaxis of cyclosporine A and mycophenylate mofetil. 224 patients were randomized.
There were four major findings:
- 1) survival results overall, regardless of treatment arm, have improved,
- 2) for children, an adequately dosed single umbilical cord blood unit is sufficient, giving a survival result of 72% at one year,
- 3) double umbilical cord blood transplant is associated with more GVHD and poorer platelet recovery but survival is comparable to an adequately dosed single unit, and
- 4) HLA mismatch is well tolerated with potentially better disease free survival in patients transplanted with HLA mismatched umbilical cord blood , a provocative finding that requires further investigation.