Use of two partially HLA-matched units of umbilical cord blood were not superior to a single unit if it contained an adequate number of hematopoietic stem cells, according to a randomized study by the Blood and Marrow Clinical Trials Network. Results were reported at the 54th Annual Meeting of the American Society of Hematology (ASH) in Atlanta.1
Single units of umbilical cord blood are used in children, but adults undergoing hematopoietic stem cell transplantation often require more units. “We hypothesized that infusing two units of umbilical cord blood would improve outcomes [in children],” explained lead author John E. Wagner, MD, Director of the Pediatric Blood and Marrow Transplant Program at the University of Minnesota in Minneapolis.
“Our findings, while unexpected, affirm that the standard transplant approach using a single unit of umbilical cord blood is optimal so long as the unit offers a sufficient number of cells. Still, the study also showed that a double–umbilical cord blood transplant, while not better than an adequate single-unit transplant, is a useful and effective strategy in those instances where an adequate single unit is not available, such as in adults,” he said. Furthermore, having verified the safety of this approach, the double umbilical cord blood model may also be a useful tool for testing new strategies focused on improving engraftment and immune recovery, he added.
The study randomly assigned 224 pediatric patients with acute leukemias to single– vs double–umbilical cord blood transplant. Importantly, all received a modified conditioning regimen containing fludarabine, which likely had a beneficial effect for all patients in this study. Both the single–umbilical cord blood and double–umbilical cord blood groups had a similar number of donor/patient mismatches.
No difference between the two treatment arms was observed in the overall rate of engraftment, Dr. Wagner continued. Both arms did better than the historical experience in children with leukemia. The rate of neutrophil recovery at day 42 was 89% with single-unit umbilical cord blood and 86% with double-unit umbilical cord blood.
The incidence of grade II–IV acute graft-vs-host disease was almost identical in both arms: 56% vs 57% (with most grade II), respectively. The rate of chronic graft-vs-host disease was 28% vs 31%.
“The risk of relapse was surprisingly low after umbilical cord blood transplant, with no real difference between the two arms,” he said. At 1 year, the relapse rate was 12% in the single [umbilical cord blood] arm vs 14% in the double [umbilical cord blood] arm. Typically, the relapse rate is 30% to 35% in pediatric patients. Dr. Wagner noted that the relapse rate could increase with longer follow-up, although this is not likely to change much since most patients are beyond 2 years post-transplant.
No significant difference in disease-free survival was seen between the two arms: 68% vs 64%. Dr. Wagner said that the results in this trial were superior to past studies and likely attributed to the modified conditioning regimen used in the trial.
The cost of transplant is an important issue, he noted. One cord unit costs on average $40,000, and two units are therefore twice as much. “Use of two units is justifiable but only in the circumstance when one unit does not contain the number of cells needed,” Dr. Wagner said, adding, “We have to continually look for ways to improve safety and reduce the cost of transplant.”
Pediatric vs Adult Patients
“This study showed there is no benefit of adding a second unit when effective conditioning is used in children,” commented Vanderson Rocha, MD, Professor at Oxford University, United Kingdom, and moderator of an ASH press conference where these findings were discussed.
“For some years, double [umbilical cord blood] transplant was assumed to produce better outcomes for adults. With reduced-intensity conditioning, we have better outcomes and lower relapse rates for adults in first remission. There is still a role for double [umbilical cord blood] transplants in adults, for whom one unit is not sufficient.” ■
Disclosure: Drs. Wagner and Rocha reported no potential conflicts of interest.
1. Wagner J, Eapen M, Carter S, et al: No survival advantage after double umbilical cord blood (UCB) compared to single UCB transplant in children with hematologic malignancy: Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501) randomized trial. 2012 ASH Annual Meeting. Abstract 359. Presented December 10, 2012.