7. Double umbilical cord blood transplantation

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. The underlying hypothesis is that the addition of the second unit will enhance engraftment and speed of hematopoietic recovery. Thirty-one adult and adolescent patients [median age 24 years (range: 13-53); median weight 73 kg (range: 48-120)] with high-risk hematologic malignancy were transplanted with two partially HLA-matched UCB units after myeloablative conditioning. Patients had AML (n = 15), ALL (n = 12), CML (n = 3) or NHL (n = 1). The median total infused dose 3.7 × 107 NC/kg (range 1.1-6.3) and 4.9 × 105 CD34/kg (range, 0.9-14.5). All patients engrafted at a median of 23 days (range 14-41) with one unit predominating. No factor (nucleated cell dose, CD34+ cell dose, HLA-match, ABO, sex, order of infusion) predicted which unit would predominate. Incidence of platelet recovery (>50,000/μL) was 73% (95% CI, 51-95) at day 180. Incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD) was 65% (95% CI, 42-88) and 17% (95% CI, 2-32) at day 100. Disease-free survival is 72% at 1 year for patients transplanted in CR with no relapse in this cohort (median follow up: 1.2 years). These data suggest that 1) double unit UCBT is safe with one unit predominating over time, 2) double unit UCBT extends the application of adults to nearly all adults and adolescents and 3) survival exceeds historical data with a single UCB unit. Validation studies at other centers are in progress.