Double Cord Blood Transplant Better Than Single in Leukemia

Roxanne Nelson

December 05, 2010

December 5, 2010 (Orlando, Florida) — A double cord blood transplant (CBT) is not only feasible but also appears to be associated with better overall outcomes than a single CBT, according to new data presented here at the American Society of Hematology 52nd Annual Meeting. This was found to be particularly true when used early in the treatment of acute leukemias.

The use of double CBT extended the indication of allogenic hematopoietic transplantation in adult patients who were unable to obtain a single CBT unit with enough cell dose. In addition, explained lead author Vanderson Rocha, MD, scientific director of Eurocord Registry, Hôpital Saint-Louis, in Paris, France, the study confirmed the lower rate of relapse in patients who received a double CBT compared with a single CBT.

Dr. Vanderson Rocha

Previous research from the University of Minnesota has already shown that patients with acute leukemia who received a double CBT enjoy a lower incidence of relapse and a similar rate of leukemia-free survival.

The rate of leukemia-free survival was also improved in this study for patients transplanted with a double CBT in first complete remission, said Dr. Rocha.

"The result is that engraftment rate is the same between single and double CBT," said Dr. Rocha during a press briefing held in advance of the presentation. "We have found and confirmed that you have higher incidence of graft-versus-host-disease [GVHD] in double CBT, but the mortality is not higher compared with single CBT."

Study Details

Dr. Rocha and colleagues undertook this study to confirm the earlier findings in a larger and more homogenous cohort of patients. They retrospectively compared outcomes after a double CBT (n = 230) with those after a single CBT (n = 377) in adult patients with acute myeloid or lymphoblastic leukemia who were in remission. The authors also separately evaluated the outcomes in patients who received a CBT while in first remission compared with those in second or third remission.

There were some differences in the 2 treatment groups. Patients who received a double CBT tended to be heavier (median weight, 68 kg vs 65 kg; P < .01), be older (median age, 37 years vs 35 years; P = .06), have a lower frequency of poor cytogenetics (32% vs 36%; P = .02), have been transplanted more recently (P < .001), and have received less antilymphocyte globulin and/or antithymocyte globulin (29% vs 70%; P < .001) when compared with those receiving a single CBT.

Diagnosis and status at the time of transplant were similar between both groups. They performed 2 separate analyses — one for patients who received transplants while in first remission and the other for patients transplanted in their second or greater remission. Differences between double and single CBT remained the same in both analyses.

First Remission

For patients transplanted in their first remission, the median follow-up was 17 months for those receiving a double CBT (n = 114) and 19 months for recipients of a single CBT (n = 203).

Unadjusted univariate analysis showed that the cumulative incidence of neutrophil recovery was similar between the 2 groups: 78% after a double CBT and 82% after a single CBT (P = .11). The incidence of acute GVHD was significantly higher in double CBT recipients, at 45% and 27% (P < .001). However, rates of chronic GVHD were similar, at 21% and 27% (P = .35), and were not statistically different.

The cumulative incidence of nonrelapse mortality was 32% for those receiving a double CBT compared with 36% in those who received a single CBT, at 3 years (P = .89). The authors also observed that leukemia-free survival was 53% after a double CBT and 39% after a single procedure (P = .09).

Recipients of a double CBT also had an increased risk for grade II to IV acute GVHD (hazard ratio [HR], 1.23; P = .005), but a lower incidence of relapse (HR, 0.74; P = .01) compared with those who received a single CBT. Multivariate analysis also showed that leukemia-free survival was improved after a double CBT compared with single CBT recipients (HR, 0.67; P = .04).

Second and Third Remission

The median follow-up in patients transplanted in second and third remission was 11 months for double CBT (n = 116) and 22 months for single CBT (n = 174) recipients. Neutrophil recovery was similar between the 2 groups (85% vs 83%; P = .57). As with patients in first remission, the incidence of acute GVHD was higher in those who received a double CBT, at 33% and 17% (P = .003), but not chronic GVHD, where it was 32% and 29% (P = .64), respectively.

The authors noted that the cumulative incidence of nonrelapse mortality at 3 years was similar for the 2 groups (34% vs 36%; P = .47). The same was true for relapse incidence: 31% and 33% (P = .68). Unlike patients in first remission, the 3-year leukemia-free survival was similar between recipients of double and single CBT (35% vs 31%; P = .48). After adjusted multivariate analysis, neutrophil recovery, acute and chronic GVHD, nonrelapse mortality, relapse incidence, and leukemia-free survival were not statistically different between the 2 transplant groups.

Leukemia-Free Advantage

The study showed that for patients in first remission, double CBT had a higher overall leukemia-free advantage, commented Karen Ballen, MD, clinical director, Leukemia Program, Massachusetts General Hospital Cancer Center, in Boston. She was not involved in the study.

"For patients with more advanced disease — those in second and third remission — this advantage was not observed," she told Medscape Medical News in an interview. "While the reasons for this are not clear, it may be that these patients don't do as well in general. So it may be more difficult to see a benefit."

Dr. Ballen also noted that single CBT was initially used in children, but recovery tended to be more delayed in adults. Although it depends on size, double CBT is more commonly used for larger patients. "We tend to use double [CBTs] for adults in the United States," she said. "American patients tend to be larger than those in either Europe or Asia."

This is an important study because it suggests that the nonrelapse mortality was similar between the 2 options, noted press conference moderator Armand Keating, MD, vice president of the American Society of Hematology and professor of medicine, director of the Division of Hematology, and Epstein Chair in Cell Therapy and Transplantation at the University of Toronto, in Ontario, Canada.

"But leukemia-free survival may be superior, and the way we need to address this is with randomized trials," he added. "There are currently 2 that are ongoing: 1 in the United States and 1 in Europe."

The study was supported by European and French grants. The authors have disclosed no relevant financial relationships.

American Society of Hematology 52nd Annual Meeting: Abstract 910. Presented December 5, 2010.

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