Single-Unit versus Double-Unit Umbilical Cord Blood Transplantation in Children and Young Adults with Residual Leukemic Disease

Abstract

A B S T R A C TWe previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single-versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of 10 ¡4 , which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 § 4.4%, and it was not significantly influenced by the MRD level: 70.7 § 5.4% in MRD-negative (<10 ¡4 ) patients (n = 72), 71.1 § 9.4% in MRD-positive patients with 10 ¡4 MRD <10 ¡3 (n = 26) and 58.8 § 11.9% in MRD-positive patients with 10 ¡3 (n = 17). In the MRD-positive group, the mean risk of relapse was significantly lower in the double-UCBT arm compared with the single-UCBT arm (10.5 § 7.2% versus 41.7 § 10.4%; P = .025) leading to a higher mean 3-year survival rate (82.6 § 9.3% versus 53.6 § 10.3%; P = .031). This difference was observed only in patients who had not received antithymocyte globulin during their conditioning regimen. In the MRD-negative group, there was no difference between the single-and the double-UCBT arms. We conclude that even in cases of positive pretransplantation MRD, UCBT in children and young adults with acute leukemia yields a high cure rate, and that a double-unit strategy may enhance the graft-versus-leukemia effect and survival in these patients.

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults

“…34,39 Additionally, MRD did not adversely impact PFS of leukemia patients supporting a robust CB-mediated graft-versus-leukemia effect as previously reported. 3,40 Very promising PFS was also observed in AML patients with high relapse risk according to their ELN classification at diagnosis and those with FLT3 ITD.…”

Umbilical Cord Blood Transplantation: Still Growing and Improving

“…The effects of sUCBT and dUCBT were compared through several studies (Table 2 ). 57 , 58 , 59 , 60 , 61 , 62 An open‐label, phase 3, multicenter, randomized trial reported by Wagner et al 58 determined the effect of the graft composition (double‐unit vs single‐unit) on 1‐year survival among patients who received the same conditioning and GVHD prophylaxis regimen. The results showed that recipients of dUCBT had no engraftment or survival benefit compared with those receiving a sufficient dose of sUCBT.…”

The Role of Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Leukemia

“…Transplantation of two UCB grafts has been proposed to overcome the limitations related to the low cell dose infused; unfortunately, in two prospective randomized studies, the double UCBT strategy did not improve the overall outcome of children and young adults with AL in the presence of a single unit of adequate cell dose, being instead associated with an increased risk of GvHD [195,196]. Despite that, it has been suggested that the double-unit strategy may enhance the GvL effect and be of particular benefit in patients with positive pre-transplant MRD [197,198]. Strategies aimed at expanding the number of UCB progenitors ex vivo and favouring stem-cell-homing in vivo are being developed with encouraging preliminary results, holding the potential to revitalize the field of UCBT in the near future [199][200][201].…”