Double umbilical cord blood transplantation after novel myeloablative conditioning using a regimen of fludarabine, busulfan, and total lymphoid irradiation.

We conducted a pilot study evaluating double umbilical cord blood transplantation (dCBT) after myeloablative conditioning with fludarabine and busulfan 3.2 mg/kg i.v. × 4, followed by total lymphoid irradiation at 400 cGy (FluBu4/TLI) for any indicated hematological disorder for patients without a suitable donor. Twenty patients with predominantly high-risk disease underwent dCBT according to protocol. The regimen was well tolerated, with mucositis as the primary observed toxicity (n = 19). The cumulative incidence of neutrophil engraftment was 89% (95% confidence interval [CI], 64% to 97%), with a median time to recovery of 16 days (range, 12 to 31 days). All evaluable patients with neutrophil engraftment achieved complete donor chimerism by day 40. The cumulative incidence of grades III and IV acute graft-versus-host disease (GVHD) at day 100 was 10% (95% CI, 2% to 27%), and the cumulative incidence of chronic GVHD was 35% (95% CI, 16% to 55%) by the end of the study. At 1 year, the cumulative incidence of treatment-related mortality (TRM) was 35% (95% CI, 16% to 55%). The leading cause of nonrelapse mortality was acute GVHD (n = 4), followed by graft failure (n = 2) and chronic GVHD (n = 1). TRM was significantly associated with a pretransplantation hematopoietic cell transplantation-specific comorbidity index score ≥ 3 (P = .005). At 1 year, disease relapse occurred in 6 patients and overall survival was 40% (95% CI, 19% to 60%). We conclude that FluBu4/TLI is an adequate preparative regiment before dCBT, providing high engraftment rates and relatively early neutrophil recovery. The best survival outcomes were seen in patients without significant comorbidities before transplantation, and outcomes are comparable to previously published dCBT studies.