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Double UCB transplant did not improve survival in children
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ATLANTA — Hematopoietic stem cell transplants with double units of transfused umbilical cord blood offered no survival advantage over transplantation with single units among a cohort of children with hematologic malignancies, according to study results presented at the 2012 ASH Annual Meeting and Exposition.
“Our findings, though unexpected, affirm that the standard transplant approach of a single umbilical cord blood unit is optimal so long as the unit offers a sufficient number of cells,” said researcher John E. Wagner, MD, director of the pediatric blood and marrow transplant program at the University of Minnesota.
John E. Wagner
Umbilical cord blood (UCB) contains a high concentration of hematopoietic stem cells. The stem cells’ unique immune profile allows for a high degree of human leukocyte antigen (HLA) mismatch. Consequently, UCB has become an increasingly popular source of hematopoietic stem cells for transplants, according to background information provided by researchers.
The optimal quantity of transplanted umbilical cord stem cells remains unclear, however.
Prior studies have demonstrated that double UCB transplant — which involves the co-infusion of two partially HLA-matched units — is effective, particularly in adults for whom a single UCB unit is inadequate.
Researchers within the Blood and Marrow Transplant Clinical Trials Network conducted a multicenter, phase 3 trial to determine whether double UCB transplant may be superior to single-unit transplant in children with blood cancers.
Thirty-eight centers enrolled 224 pediatric patients with acute leukemia between December 2006 and February 2012.
The investigators randomly assigned patients to receive either a single-unit (n=113) or double-unit (n=111) UCB transplant. The average number of cells was 3.9x 107 per kg in the single units and 7.2 x 107 per kg in the double units.
Researchers stratified patients by age and transplant center. The patients’ primary disease, disease risk, sex, age, race, ethnicity, performance score and HLA-match were balanced between the two study groups, according to investigators.
The investigators also modified the conditioning regimen for all patients — eliminating antithymocyte globulin and replacing it with fludarabine — to try to reduce the risk of infectious disease complications after transplant.
OS served as the primary endpoint. Researchers also evaluated other transplant outcomes, including blood and marrow recovery time, risks of acute and chronic graft-versus-host disease (GVHD), and transplant-related mortality and relapse.
After a median follow-up of 25 months, 92% of all patients were in remission. OS was 71% among patients assigned to single-unit transplant and 66% among patients assigned to double-unit transplant.
Researchers observed similar DFS (68% for single-unit transplant vs. 64% for double-unit transplant) and rates of relapse (12% for single-unit transplant vs. 14% for double-unit transplant) between the two groups.
The overall rate of GVHD was 57% in both study arms; however, rates of grade 3-4 GVHD were higher among patients assigned to double-unit transplant (23% vs. 14%). The increased incidence of severe GVHD may be due to the increased number of transplanted hematopoietic stem cells, the researchers said.
“The success rates in terms of engraftment and overall survival were substantially higher than what we would have expected based on the historical data set,” Wagner said during a presentation. “Part of it may have been due to supportive care, and part of it may be because of the new conditioning regimen.”
Although double UCB transplant did not improve survival, results suggest that option is an acceptable alternative for patients — particularly adults — for whom a single unit of cells is insufficient, Wagner said.
“We need to focus our efforts on the development of new strategies that will enhance the speed of engraftment and immune recovery,” Wagner said. “The double umbilical cord blood model may be a useful tool for achieving that goal.”
For more information:
Wagner JE. Abstract #359. Presented at: the 2012 ASH Annual Meeting and Exposition; Dec. 8-11, 2012; Atlanta.
Disclosure: The researchers report no relevant financial disclosures.