5: Double Umbilical Cord Blood Transplantation after Myeloablation
Year: 2007
Type: article
Abstract: Cryopreserved umbilical cord blood (UCB) has been investigated as a potential strategy for augmenting the pool of acceptable donors, reducing the risks of acute and chronic graft-versus-host disease (GVHD) and improving survival. Cell dose, however, has clearly been identified as a major limitation, often preventing the consideration of UCB for adult recipients. Recipients of <2.5 × 107 nucleated cells/kg have slow hematopoietic recovery and significantly lower incidence of engraftment. Therefore, we explored the potential of infusing two partially HLA matched units to augment cell dose in patients who did not have an UCB graft containing <2.5 × 107 nucleated cells/kg. The underlying hypothesis is that the addition of the second unit will enhance engraftment and speed of hematopoietic recovery. One-hundred and twenty-two patients [median age 23.2 years (range: 2.9-45.8); median weight 64 kg (range: 12.6-148.6)] with high-risk hematologic malignancy were transplanted with a partially HLA-matched UCB graft (70% received two units) after a single myeloablative conditioning consisting of fludarabine 75 mg/m2, cyclophosphamide 60 mg/kg and total body irradiation 1320 cGy. All received cyclosporine and mycophenolate mofetil posttransplant immunoprophylaxis. Patients had AML (n=51), ALL (n=46), CML (n=10), MDS (n=4) or NHL (n=11). The median total infused dose was 4.4 × 107 NC/kg (range 1.1-13.9). The incidence of neutrophil recovery was 91% (95% CI, 86-96) at a median of 23 days with no difference observed in recipients of one or two units. Only CD34 cell dose predicted incidence and speed of recovery. After engraftment, one unit predominated in >90% with no factor (nucleated cell dose, CD34+ cell dose, HLA-match, ABO, sex, or order of infusion) predicting which unit would predominate long term. Incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD) was 55% (95% CI, 44-66) and 17% (95% CI, 9-25) at day 100 with an increased incidence of grade II disease only in recipients of two units. Incidences of transplant-related mortality and relapse was 25% (95% CI, 17-33) at 1 year and 22% (95% CI, 12-32) at 2 years, respectively. Probabilities of overall and event-free survival are 59% (95% CI, 49-69) and 51% (95% CI, 40-62) at 2 years, respectively. Notably, recipients of two units had a trend toward reduced relapse and improved event-free survival. These data suggest that 1) double unit UCBT is safe with one unit predominating over time, 2) double unit UCBT may extend the application of UCB to nearly all adults and adolescents, and 3) double UCBT may be associated with lower relapse and higher survival in those with acute leukemia in complete remission. A NIH-CTN sponsored, multi-institutional randomized trial comparing outcomes in recipients of single versus double UCB transplantation is open for accrual.
Authors: John E. Wagner, Claudio Brunstein
Institution: University of Minnesota
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2159366792