One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers

Abstract

BACKGROUND Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. METHODS Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. RESULTS Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor–recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P = 0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II–IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. CONCLUSIONS 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 GVHD.

Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups

“…The merits of CBT are likely related to the low incidence of significant GvHD despite an increase in early mortality due to delayed hematopoietic and immunological recovery and graft failure after single CBT. [23][24][25] In the Holtan study, relative risks of GRFS events after CBT using mostly double units were approximately 2.0 compared with 6/6 HLA-matched sibling BMT, while hazard ratios after CBT compared with 6/6 HLA-matched sibling BMT in our study were lower at ranges between 1.20 and 1.35 regardless of patient age and disease risk. The difference between the studies could be accounted for by the lower risk of severe GvHD after single CBT compared with double CBT, 23,24 and by the lower risk of severe GvHD in the Japanese population compared with the Caucasian population.…”

“…[23][24][25] In the Holtan study, relative risks of GRFS events after CBT using mostly double units were approximately 2.0 compared with 6/6 HLA-matched sibling BMT, while hazard ratios after CBT compared with 6/6 HLA-matched sibling BMT in our study were lower at ranges between 1.20 and 1.35 regardless of patient age and disease risk. The difference between the studies could be accounted for by the lower risk of severe GvHD after single CBT compared with double CBT, 23,24 and by the lower risk of severe GvHD in the Japanese population compared with the Caucasian population. 4 Consistent with the Holtan study, 1 our study found that 6/6 HLA-matched sibling BMT was associated with higher GRFS compared with other graft sources.…”

Umbilical cord blood donation: public or private?

“…17,24 Various strategies to approach these challenges are under study. The Blood and Marrow Transplant Clinical Trials Network conducted a study to determine whether children with hematological malignancies would have improved survival after a double UCBT, as compared with single UCBT (BMT-CTN 0501).…”

“…This study did not demonstrate an advantage for double UCBT in children where a single UCB provided an adequate cell dose. 24 ADULT UCBT Initial studies in single UCBT were hampered by delayed engraftment, leading to a high transplant-related mortality. 25 Outcome results have improved with better patient selection, better supportive care including growth factors, prophylactic and preemptive antiviral treatment and the choice of UCBT units with higher nucleated cell doses/kg ( Figure 1).…”

Cellular engineering and therapy in combination with cord blood allografting in pediatric recipients

“…11,12 Although initial studies of double UCBT in adults appeared to be encouraging, 13,14 a recent prospective randomized trial of single versus double UCBT in children with hematological malignancies demonstrated no improved overall survival and a significant increase in severe acute GVHD and chronic GVHD in double cord transplant recipients. 15 New approaches are needed to accelerate the rapidity of neutrophil engraftment, and cellular immune reconstitution, reduce primary graft failure, decrease transplantrelated mortality and subsequently enhance OS following UCBT. This report summarizes a few new therapeutic approaches including ex vivo expansion, using engineered cord blood (CB) CD34 + cells expressing the Notch ligand Delta 1, co-culture expansion of mesenchymal progenitor cells (MPC) with CB progenitor cells, the addition of third party human placentaderived stem cells (HPDSCs) with single or double UCBT and the expansion and utilization of CB-derived natural killer (NK) cells.…”