Kinetics of myeloid and lymphocyte recovery and infectious complications after unrelated umbilical cord blood versus HLA‐matched unrelated donor allogeneic transplantation in adults

Abstract

SummarySources for allogeneic stem cells for patients with haematological disorders lacking a histocompatible sibling donor include matched unrelated donor (MUD) and umbilical cord blood (UCB). A total of 51 patients with haematological disorders, treated with myeloablation and transplantation with either unrelated human leucocyte antigen (HLA) partially matched UCB (28 patients) or HLA-matched MUD grafts (23 patients) during 1997-2003, were evaluated for life-threatening infections, haematological reconstitution, graft versus host disease, relapse and event-free survival (EFS). The median duration of neutropenia after transplantation was longer (29 d vs. 14 d) in the UCB group. The probability of donorderived neutrophil engraftment by day 42 was 0AE86 [95% confidence interval (CI) 0AE71-1AE0] in UCB recipients versus 0AE96 (95% CI 0AE87-1AE0) in MUD recipients surviving >28 d. Overall infection rates were higher in UCB recipients, particularly at the early time points (before day +50) after transplantation. Graft failure occurred in five UCB recipients and two MUD recipients and was associated with the occurrence of bacteraemia during neutropenia. The EFS at 3-year follow-up was 0AE25 in UCB and 0AE35 in MUD recipients. UCB transplantation in adults is associated with delayed neutrophil and lymphocyte recovery compared with MUD grafting, and higher rates of bacteraemia at early time points after transplantation.

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

“…Recent reports indicate that the rate of infections during the early post-transplantation period is higher in adult patients transplanted with HLA mismatched unrelated UCB, while overall rates of infections at later time points are similar to that observed in unrelated adult donor transplant recipients [60]. Mechanisms responsible for this event may be related to the prolonged duration of neutropenia and lymphopenia after infusion of smaller numbers of total graft nucleated cells and CD34+ cells.…”

“…The slow process of immune reconstitution together with post-engraftment immunosuppression creates an immunologic environment whereby the host is susceptible to opportunistic infections [54][55][56] as well as virally induced malignancies [57,58]. Recipients of unrelated donor or HLA non-identical transplants appear to have a higher rate of infectious complications than recipients of matched sibling allogeneic grafts [59][60][61]. GvHD and its treatment further delays immune recovery after allogeneic transplantation and may account for the higher rate of delayed immune reconstitution in recipients of unrelated versus related donor grafts.…”

“…Several reports outlining the kinetics of immune recovery after UCB transplantation in adults and children point to slow T-cell recovery [60], [62][63][64][65][66] compared with published reports after conventional graft allogeneic transplantation [66][67][68][69][70][71]. Recent studies have evaluated the immune function of adult UCB patients during the first two years post-transplant.…”

“…The Case Western Reserve University transplant group evaluated patients with hematologic disorders treated with myeloablative regimen and transplantation with either UCB or HLA-matched unrelated (MUD) grafts, for life-threatening infections, hematologic reconstitution, GvHD, relapse and event-free survival [60]. The median duration of neutropenia after transplantation was longer (29 vs. 14 days) in the UCB group.…”

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

“…5 However, despite these initial encouraging results, opportunistic infections remain a matter of concern after cord blood transplantation (CBT) as a consequence of delayed hematopoietic and immune reconstitution. [1][2][3][4]6 Indeed, different studies documented a higher incidence of severe bacterial infections accountable for early mortality in adult patients receiving CBT. 3,7,8 Data related to viral infections after CBT (especially for Herpesviridae) are still relatively scarce.…”