unrelated cord blood transpalntation and post-transplant cyclophosphamide

he number of unrelated cord blood transplants (UCBT) are declining in Europe,1 despite comparable outcome with grafts using unrelated donor peripheral blood or bone marrow.2 The reasons for the decline may be due to the well-known slow engraftment and delayed immune reconstitution of UCBT, which may result in a significant risk of infections and non-relapse mortality (NRM).3,4 Neutrophil and platelet recovery can be shortened by direct intra-bone injection of CB cells,5 but immune recovery remains an issue, especially when anti-thymocyte globulin (ATG) is used in the conditioning regimen.5 In the absence of ATG, grade III-IV acute graft versus host disease (GvHD) is reported to be 21%,6 and when ATG is added in the transplant platform, GvHD is reduced (15%),6 but immune reconstitution is delayed, leading to infectious complications, and late viral infections.4,7,8 The crucial role of ATG and the risk of over or under exposure is further proven by the attempt to optimize ATG dose based on lymphocyte counts, rather than patient’s weight,9 and by carefully assessing the speed of CD4 recovery according to ATG dosing pre-transplant.10 An additional reason for the decline in numbers of UCBT is the competition of HLA haploidentical transplants (HAPLO),11 especially performed with post-transplant cyclophosphamide (PT-CY), as first described by the Baltimore group.12 We have been particularly impressed with the speed of immune recovery of HAPLO transplants with PT-CY,13 with median CD4 counts on day +100 (190/μl) comparable to CD4 counts after HLA identical sibling grafts (229/μl), and significantly higher as compared to unrelated and cord blood grafts receiving ATG for GvHD prophylaxis.13