[Umbilical cord blood cell transplantation from an unrelated donor: dual transplantation].

Abstract

Our team conducted an original procedure of hematopoietic transplantation of umbilical cord blood (UCB) from an unrelated donor. The procedure consists of co-infusing hematopoietic stem cells selected from the blood of a third-party donor; it is conceived as a tool to shorten the engraftment period without preventing the engraftment of the UCB, even when using units with relatively low cell content and a low HLA compatibility. Between 1999 and 2008 we performed 64 transplantations in 60 adult patients (35 men and 25 women) with a median age of 34 years (range: 76-60) and a median weight of 70 kg (range: 43-95), all of whom were diagnosed with a high risk hematologic neoplasm (leukemia in most cases). Fludarabine, cyclophosphamide, ATG, and whole body irradiation or busulfan were used as conditioners. UCB was infused at medians of 2.4 x 107 CNT/kg (range: 1.14-4.30 x 107), 0.11 x 106 CD34+/kg (range: 0.035-0.37 x 106). Then, hematopoietic stem cells selected from the third-party donor were infused (2.43 x 106/kg [range: 1.05-3.34 x 106], with 0.3 x 104 CD3+/kg [range: 0.05-1.56 x 104]). Granulocyte engraftment occurred (ANC > 0.5 x 109/L) at a median of 10 days (range: 9-34 days), and the granulocyte engraftment of the UCB occurred in 21 days (range: 13-57 days). Complete UCB chimerism was observed in 37 days (range: 11-186 days) (previously double complete chimerism, presence of third-party donor and of cord) and platelet engraftment > 20 x 109/L in 33 days (range: 13 98 days) and > 50 x 109/L in 58 days (range: 14-106 days). Overall 3-year survival reached 51%, and 5 10 year-survival was 47% (plateau). Disease-free survival was 48% at three years, and 45% at 5 to 10 years; the mean follow-up of survivors was 48 months (range: 13-123 months). (Kaplan-Meier). In conclusion, early granulocyte recovery occurred thanks to a foster engraftment of hematopoietic stem from the third-party donor, which are not HLA-restricted; this is associated with a lower morbidity and mortality from infections secondary to neutropenia. There was also a high rate of engraftment and final full UCB chimerism, even with non-histocompatible UCB units (2/6 HLA mismatches) and with relatively low cell counts. In most cases, a single unit of UCB was sufficient. The incidence of severe GVHD and the percentage of relapses have been low. Opportunistic infections have occurred over a long period of time. This procedures makes allogeneic hematopoietic transplantation accessible to almost all patients.