Double umbilical cord blood transplantation for children and adolescents

Abstract

Umbilical cord blood transplantation (UCBT) with two units has been conducted with promising results in adults to overcome the limitation of low cell numbers. In an attempt to improve the outcomes, double UCBT was performed in children and adolescents. Sixty-one patients, including 44 acute leukemia, and 17 other hematologic diseases, received double UCBT. Donor-type engraftment achieved in 82% of patients. Except one patient with persistent mixed chimerism of two units, other 49 patients showed dominancy of one unit and only the CFU-GM was significant factor influencing dominancy. The event-free survival (EFS) of leukemia and other hematologic disease were 59% and 53%, respectively, and the EFS of acute leukemia patients who received transplant in first or second CR (68.6%) was significantly better than in those with advanced disease (22.2%) (P = 0.007). Among the factors influencing outcomes, low cell dose difference between two units (TNC difference/TNC of large unit <15%) were associated with higher TRM, relapse, and lower EFS. Double UCBT was a promising modality of transplant in children and adolescence. However, engraftment and other results were not so satisfactory yet. To improve the outcomes, development of new selection guideline, probably including cell dose difference between two units and technology to enhance engraftment and reduce transplantation-related mortality are warranted.

Fig. 1

Survival data. a Event-free survival (EFS) of 61 patients was 57.4%. b The EFS of acute leukemia and other hematologic disease was 59.1% and 52.9%, respectively. (P = 0.524). c Among acute leukemia patients the EFS was significantly better in patients who received UCBT in first or second complete remission (CR) (68.6%) than in those with advanced disease (22.2%) (P = 0.007). d The EFS was significantly worse in ALL patients with advanced disease (0%) than those in first CR (66.7%) or second CR (66.7%) (P = 0.007). e In AML patients, there was no difference in EFS in patients with advanced disease (40.0%), first CR (75.0%) or second CR (50.0%) (P = 0.447)

Fig. 2

The low cell dose difference (TNC difference/large unit <15%) between two units and outcomes. a The EFS of patients who received two UCB units with a low cell dose difference (25.0%) was significantly worse than that of other patients (73.2%) (P = 0.000). b The TRM of patients with a low cell dose difference (56.5%) was higher than that of other patients (13.2%), significantly (P = 0.001). c The relapse rate of acute leukemia was significantly higher in patients with a low cell dose difference (50.6%) than in others (7.7%) (P = 0.002)