Hematologic Cancers: Umbilical Cord Transplantation – One vs Two Units

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 55455MedicalResearch.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.

Medical Research: What should clinicians and patients take away from your report?

Dr. Wagner: The primary ‘take away’ is that an adequate single umbilical cord blood unit even if mismatched is associated with a high probability of survival.  Improvements in conditioning and supportive care likely play a role and the results presented provide a new standard by which future alterations might be compared.  In addition, for those without a suitable single umbilical cord blood unit based on cell dose, a double UCB transplant provides similar results, extending the option of umbilical cord blood as a useful graft source.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Wagner: The reported outcomes lead to new questions.  In multivariate analysis, disease free survival was adversely affected by the diagnosis of acute myelocytic leukemia, non-white race and HLA match.  The finding that HLA match was associated with a lower disease free survival (compared to recipients of a mismatched graft) is provocative and warrants further investigation.  Perhaps more HLA mismatch is associated with lower relapse risk.  In addition, pace of hematopoietic recovery remains slow despite improvements in overall incidence of engraftment in the current study.  Ex vivo expansion of hematopoietic stem cells culture or strategies that will enhance homing to the marrow microenvironment are under investigation currently

Citation:

One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers

John E. Wagner, Jr., M.D., Mary Eapen, M.B., B.S., Shelly Carter, D.Sc., Yanli Wang, M.S., Kirk R. Schultz, M.D., Donna A. Wall, M.D., Nancy Bunin, M.D., Colleen Delaney, M.D., Paul Haut, M.D., David Margolis, M.D., Edward Peres, M.D., Michael R. Verneris, M.D., Mark Walters, M.D., Mary M. Horowitz, M.D., and Joanne Kurtzberg, M.D. for the Blood and Marrow Transplant Clinical Trials Network

N Engl J Med 2014; 371:1685-1694
October 30, 2014DOI: 10.1056/NEJMoa1405584

 

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