Since the National Health Insurance began allowing UCBT in children under the age of 16 years in January 2003, the number of UCBT cases has increased dramatically in Korea. A multicenter analysis of 236 children who underwent UCBT in Korea suggested that UCBT was a reasonable alternative as an HSC source9)
The data in the present study indicate that allogeneic HSCT for patients with acute leukemia can result in durable EFS between 46% and 49% at 5 years using MRD, URD, or UCB sources. Remarkably, the OS was similar between the MRD, URD, and UCB HSCT groups, which was nearly 55% at 5 years. Importantly, our results are not inferior to other studies. A Eurocord study of children with acute leukemia showed 2-year OS of 49% and 35% in URD and UCB groups, respectively6)
. In another study, the 5-year leukemia free survival was 41% in recipients of MRD and 43% in recipients of UCB in children with ALL in second CR, respectively10)
. According to the studies of HSCT outcomes that included adult data, the survival of HSCT using UCB was comparable to HSCT using URD and even MRD11
The adjusted risk of acute and chronic GVHD was not higher in transplants from UCB than transplants from MRD, despite a high degree of disparity in HLA between donor and recipient in the UCB group. Although most UCB recipients received ATG as a part of conditioning regimen, the use of ATG was not associated with the incidence of acute and chronic GVHD (P
=0.55 and P
=0.43, respectively). From the early experiences of UCBT, the incidence of GVHD was less than expected given the degree of HLA disparity. The exact reasons for the relatively lower incidence of GVHD are unknown, but likely result from the functional immaturity of the infused lymphocytes, including decreased cytotoxicity, an altered cytokine profile, decreased HLA expression and increased regulatory T-cells15)
. However, graft-versus-leukemia (GVL) effect might be preserved in transplants from UCB, which indicates a trend toward a lower incidence of relapse in the UCB group (). The results in the present study are in agreement with the previous reports suggesting that there is no increased risk of leukemia relapse when UCB is used as a stem cell source6)
. Furthermore, Verneris et al.16)
suggested that double-unit UCBT might decrease the risk of relapse due to enhanced GVL effect. In the present study, most recipients of UCB (75.6%) underwent double-unit UCBT and we also found a trend toward less relapse in recipients of UCB ().
The success of UCBT has been limited by the low cell number, which results in a higher rate of graft failure, delayed hematopoietic recovery, and increased infection complications. In the present study, we also found that neutrophil and platelet recovery was delayed significantly in the UCB group compared to the other HSC sources. In addition, the incidence of graft failure was higher than other HSC sources (). The delayed hematopoietic recovery in the UCB group might adversely affect recipients, since the NRM was significantly higher in the UCB group, which was mainly due to infection. To overcome these engraftment problems, several clinical experiments with ex vivo expanded cord blood cells have been explored, which have not resulted in a clinical benefit to date17
. Recently, mesenchymal stem cells (MSCs) were investigated to support hematopoiesis in HSCT when co-transplanted with HSCs, and several studies have shown positive results19
. In this context, we assessed the co-transplantation of MSCs with UCBT in our center as a way to overcome the cell dose limitation of UCBT and the initial results were promising (SHL, manuscript submitted Aug 2011). We also found in an animal model that the augmentation of HSC engraftment with MSCs co-transplantation was dependent on the number of MSCs implanted21)
. Therefore, the benefit of MSCs co-transplantation may facilitate the application of UCBT in patients lacking a suitable donor, even in adults, and may further decrease the complications associated with low cell number. Importantly, long-term follow-up is needed to assess the influence of co-transplantation with MSCs on the relapse of leukemia.
The limitation of this study was that patients were not randomized to each group. Although UCBT was performed, when there was no suitable HLA-MRD or unrelated adult donor available, several factors such as the urgency of HSCT, cell dose, HLA typing, and the size of the patient were taken into account for choosing the stem cell sources. However, the patient characteristics among the groups were very similar in our study.
In conclusion, this study has shown that survival in the MRD, URD, and UCB groups was similar, but that the type of complications differed, with a higher occurrence of acute and chronic GVHD in the URD group, higher trend of occurrence of relapse in the MRD group, and more NRM in the UCB group. These findings suggest that both URD and UCB represent alternative stem cell sources for children with acute leukemia who lack a MRD donor. Moreover, the rapid availability of a UCB may be a particular advantage for patients who require urgent transplantation.