ORLANDO – A large retrospective analysis of adult patients with acute leukemia suggests that double-unit transplantation of cord blood from two unrelated donors may be better than single-unit transplants despite more graft-vs.-host disease among the double-unit recipients.
Dr. Vanderson Rocha
Patients given two units of cord blood while in their first complete remission had a significantly higher rate of leukemia-free survival and lower rate of relapse compared with single-unit recipients, Dr. Vanderson Rocha reported at the annual meeting of the American Society of Hematology. No benefit was seen among patients transplanted when they were in second or third remissions.
The study confirms that double-unit transplants are feasible and can lead to better outcomes, but the results still need to be confirmed by randomized trials already underway in Europe and the United States, according to Dr. Rocha, scientific director of the Eurocord Registry at Hôpital St. Louis in Paris.
Transplantation of hematopoietic stem cells from umbilical cord blood was initially done in children. Although the practice has spread to adult patients, the number of cells in a single unit of cord blood often is not sufficient for larger recipients. Hence, many centers have started to do double-unit unrelated cord blood transplantation, which was found to be beneficial in research from the University of Minnesota (Blood 2009;113:2410-5).
Eurocord and the Acute Leukemia Working Party (a part of the European Group for Blood and Marrow Transplantation) undertook the retrospective analysis to see whether the Minnesota results would be reproducible in a registry-based study. Collecting data on adult patients with acute myeloid or lymphoblastic leukemias, the investigators found 230 who had undergone double-unit transplants and 377 given single units in European centers from 1998 to 2009.
Although the overall rates of leukemia-free survival were not significantly different statistically at 2 years, the double-unit group fared better at 44% vs. 35% of the single-unit recipients. Separating the population by number of remissions, the investigators found significant benefits for the double-units among early leukemia patients transplanted while in their first remissions.
Dr. Rocha reported the 2-year incidence of relapse was 15% in this group vs. 25% (P = .03) in the single-unit group. The leukemia-free survival rate was also improved at 53% vs. 39% (hazard ratio, 0.57; P = .04).
Double-unit recipients paid a price in more grade II-IV acute graft vs. host disease – 36% vs. 25% in the single-unit group (P = .007). Dr. Rocha noted that mortality was not higher, however, at 33% with two units and 32% in the single-unit group.
Review of the patient populations showed that those receiving double units tended to be larger with a median of 68 kg vs. 65 kg in the single-unit group (P less than .001). The double-unit transplants also tended to be more recent and have a shorter follow-up at a median of 14 months vs. 20 months for the single unit group. Median age was similar, however, at 37 years and 35 years, respectively, as were most other patient characteristics, including distribution of leukemia by type, status by first, second, or third remission at time of transplant.
More poor-risk cytogenetics were seen in the single-unit group (36% vs. 32%, P = .02). The single-unit group also was significantly more likely to have myeloablative conditioning, antithymocyte globulin/antilymphocyte globulin (ATG/ALG), and graft-vs.-host disease prophylaxis (P less than .001).
Not surprisingly, the double-unit recipients were infused with more nucleated cell: 3.7 x 107 vs. 2.6 x 107 (P less than .001). In response to audience questions, Dr. Rocha said the investigators looked for a cell-dose effect, but could not find a cell-dose cut-off based on the retrospective analysis. Time to neutrophil recovery was similar.
Dr. Armand Keating
Dr. Armand Keating, professor of medicine, director of the division of hematology, and Epstein Chair in cell therapy and transplantation at the University of Toronto, described the study as important during a press briefing which he moderated. It suggests that mortality may be the same, he said, but leukemia-free survival could be superior. Like Dr. Rocha, he anticipated that the ongoing randomized trials could resolve the issue.
Even if double-cord blood transplants prove superior, the investigators noted that cost could be an obstacle. Storing large inventories of cord blood is expensive – so much so that another press briefing panelist, Dr. Joseph H. Antin of the Dana-Farber Cancer Institute, Boston, said his institution considered setting up a program only to find it would cost 10 years to recoup the initial cost.
The price of a single unit of cord-blood ranges from €20,000 to €25,000 (euros) in Europe and $30,000 to $35,000 in the United States, Dr. Rocha said, adding that some centers might discount the price of a second unit in a double transplant.