Two- vs One-Unit Cord Blood Transplantation Does Not Improve 1-Year Overall Survival in Children and Adolescents With Hematologic Cancers
In a phase III trial reported in The New England Journal of Medicine, Wagner et al found that use of two units vs one unit of umbilical cord blood in hematopoietic stem cell transplantation did not improve 1-year overall survival in children and adolescents with hematologic cancers. Use of one unit was associated with improved platelet recovery and lower rates of grade III and IV acute and extensive chronic graft-vs-host disease.
It has been hypothesized that increasing the number of hematopoietic cells beyond that contained in a single unit of cord blood might hasten hematopoietic recovery and improve outcomes, with data from some studies suggesting better outcomes with use of two units compared with historical controls receiving a single unit.
Study Details
In this open-label trial, 224 patients aged 1 to 21 years with hematologic cancers were randomly assigned between December 2006 and February 2012 to undergo two-unit (n = 111) or one-unit transplantation (n = 113). Patients received fludarabine at 75 mg/m2, 1,320 cGy of total-body irradiation, and cyclophosphamide at 120 mg/kg followed by infusion of cord blood units. Graft-vs-host disease prophylaxis consisted of cyclosporine given through day 180 with subsequent tapering and mycophenolate mofetil given until day 45 or longer in cases of active graft-vs-host disease. The primary endpoint was 1-year overall survival.
The one-unit and two-unit treatment groups were generally balanced for age (median, 10.4 and 9.9 years), sex (51% and 63% male), race (71% and 77% white), Lansky or Karnofsky performance status (100 in 51% in both), degree of donor-recipient HLA matching (3/6, 4/6, 5/6, and 6/6 in 1% and 2%, 39% and 44%, 46% and 43%, and 14% and 11%), and disease type (acute myeloid leukemia in 35% and 34%, acute lymphocytic leukemia in 54% and 52%, myelodysplastic syndrome in 4% and 12%), and disease status at transplantation.
No Survival Difference
Median follow-up for surviving patients was 26.4 months. The 1-year overall survival rate was 65% (95% confidence interval [CI] = 56%–74%) in the two-unit group vs 73% (95% CI = 63%–80%) in the one-unit group (P = .17; hazard ratio [HR] = 1.34, P = .20, after adjustment for disease type). One-year disease-free survival was 64% vs 70% (P = 0.11; HR = 1.48, P = .08 after adjustment for leukemia type, race, and HLA match score). There were also no differences between groups in neutrophil recovery (88%, median of 23 days, vs 89%, median of 21 days; P = .29), treatment-related death (22% vs 19%, P = .43), relapse at 1 year (14% vs 12%, P = .12), infections, immunologic reconstitution, or grade II to IV acute graft-vs-host disease (P = .78).
Patients in the one-unit group had significantly better platelet recovery (78%, median of 58 days, vs 65%, median of 84 days; P = .04), and lower rates of grade III and IV acute graft-vs-host disease (13% vs 23%, P = .02) and extensive chronic graft-vs-host disease (9% vs 15%, P = .05).
The investigators concluded: “We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of [graft-vs-host disease].”
John E. Wagner, Jr, MD, of the University of Minnesota Medical School, Minneapolis, is the corresponding author for The New England Journal of Medicine article.
The study was funded by the National Heart, Lung, and Blood Institute and National Cancer Institute. For full disclosures of the study authors, visit www.nejm.org.
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