Serious Infections after Unrelated Donor Transplantation in 136 Children: Impact of Stem Cell Source

Abstract

How the infection risks compare after umbilical cord blood (UCB) and bone marrow (BM) transplantation is not known. Therefore, we compared serious infections in the 2 years after pediatric myeloablative unrelated donor transplantation with unmanipulated BM (n = 52), T cell-depleted (TCD) BM (n = 24), or UCB (n = 60) for the treatment of hematologic malignancy. Overall, the cumulative incidence of 1 or more serious infections was comparable between groups (BM, 81%; TCD, 83%; UCB, 90%; P = .12). Furthermore, by taking all serious infections into account and using multivariate techniques with unmanipulated BM as the reference, there were also no significant differences between groups (TCD relative risk [RR], 1.6; P = .10; UCB RR, 1.0; P = .84). Within the time periods days 0 to 42, days 43 to 100, and days 101 to 180, the only difference was a greater risk of viral infections from days 0 to 42 in TCD recipients (RR, 3.5; P = .02). Notably, after day 180, TCD recipients had a significantly increased infection risk (RR, 3.1; P = .03), whereas the risk in UCB recipients (RR, 0.5; P = .23) was comparable to that in BM recipients. Other factors associated with an increased infection risk in the 2 years after transplantation were age > or = 8 years, graft failure, and severe acute graft-versus-host disease. These data suggest that the risk of serious infection after pediatric UCB transplantation is comparable to that with unmanipulated BM.

Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo

“…A drawback of UCBT is the delay in reconstitution of T-cell immunity, which increases opportunistic infections. [34][35][36] Treatment of Adenovirus, BK virus, and CMV is challenging, and many UCBT recipients have complications from all 3 viruses. Prior work suggested that recovery of protective T-cell immunity to CMV after UCBT depended on de novo thymopoiesis, which is typically measurable after day 100.…”

Early identification and management of graft failure after unrelated cord blood transplantation

“…First, recipients of UCBT are at increased risk of viral infections due to lack of adoptive transfer of donor immunity. [19][20][21] The additional course of immunosuppression prior to second UCBT might have further promoted viral reactivation in our patients. Finally most patients required treatment for chronic GVHD, which could have also contributed to the risk of infection.…”

Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children

“…[1][2][3][4][5] These observations indicate that cord blood-derived immune cells have unique immune properties that allow for allogeneic tolerance while preserving the GVL effect.…”