Cord blood transplantation: evolving strategies to improve engraftment and immune reconstitution

For many patients with relapsed or high-risk hematologic malignancies, allogeneic stem cell transplantation offers the best hope for cure. For patients lacking a suitable family or unrelated donor, umbilical cord blood provides a promising alternative graft source. Dramatic advances in cord blood transplantation (CBT) have been made in the past 2 decades, leading to a rapid expansion of CBT programs worldwide.

Promising new strategies, including double CBT and ex-vivo graft engineering, have improved myeloid and platelet engraftment rates and kinetics. However, delayed immune reconstitution and associated infectious morbidity and mortality remain a significant challenge, especially in adult CBT recipients. In adults, both impaired recipient thymopoiesis and the lack of transferred memory cells contribute to delayed T cell recovery, resulting in an increased risk of opportunistic infections.

Novel clinical approaches in CBT have improved outcomes, especially those associated with delays in myeloid and platelet engraftment. However, delayed immune reconstitution remains a great challenge. Novel strategies, including graft engineering approaches capable of improving T cell recovery, and pharmacologic interventions capable of preserving thymopoiesis and facilitating the recovery of a diverse functional T cell repertoire are being pursued; these approaches have great potential to further improve outcomes after CBT.