Double Cord Blood Transplantation: Co-Operation or Competition?

Abstract

Over the last two decades umbilical cord blood (UCB) transplantation (UCBT) is increasingly used for a variety of malignant and benign hematological and other diseases. The main factor that limits the use of UCB to low weight recipients, mainly children and adolescents, is its low progenitor cell content. Various alternatives have been exploited to overcome this difficulty, including the transplantation of two UCB units (double umbilical cord blood transplantation, dUCBT). Following dUCBT, donor(s) hematopoietic stem cells (HSC) can be detected in the peripheral blood of the recipient as soon as 14 days post-transplantation. Sustained engraftment of HSC from one or both donors can be observed- dominance or mixed chimerism respectively, although single donor unit dominance has been observed in over 85% of patients. The underlying biology, which accounts for the interactions both between the two infused UCB units- cooperative or competitive, and with the recipient’s immune system, has not been elucidated.

Double Umbilical Cord Blood Transplantation: Relevance of Persistent Mixed-Unit Chimerism

“…The mechanism of single UCB unit dominance has been investigated by many groups and is most likely multifactorial. Specifically, this condition appears to involve intrinsic features of the UCB units, such as homing properties and proliferative potential of hematopoietic cells, graft-versus-graft immune interactions mediated by T cells, as well as graft-versus-host immune interactions [53][54][55]. Understanding those immune interactions may help us predict the dominant unit, and more importantly, could yield insights into the mechanisms of GVHD and GVL responses and improve outcomes.…”

Improving The Efficacy And Availability Of Stem Cell Transplant Therapies For Hematopoietic Stem Cell Transplantation

“…To overcome the limitation of cell dose, infusion of two partially HLA-matched cord units has been adopted [39] although whether interactions between the CB units are cooperative or competitive is not so clear [40]. This approach has also not reliably demonstrated a reduction in time to donor engraftment, with reported median neutrophil and platelet engraftment times ranging widely between 12-32 days and 41-105 days, respectively [41].…”

Umbilical cord blood for cardiovascular cell therapy: from promise to fact

“…11 The most marked limitation in the use of UCB is its low progenitor cell concentration. Thus, doi: 10.1111/j.1749-6632.2012.06515.x experimentation and clinical practice have focused on ex vivo expansion of UCB-derived stem cells 12 and the transplantation of two UCB units, 13 mainly for the treatment of hematological malignancies. Double UCB transplantation offers many immunological benefits, including the reduction of graft versus host disease severity 14 and enhanced engraftment of hematological progenitors.…”