Immune Reconstitution after Double Umbilical Cord Blood Stem Cell Transplantation: Comparison with Unrelated Peripheral Blood Stem Cell Transplantation

Abstract

Double umbilical cord blood (DUCB) transplantation is an accepted transplantation strategy for patients without suitable human leukocyte antigen (HLA)-matched donors. However, DUCB transplantation is associated with increased morbidity and mortality due to slow recovery of immunity and a high risk of infection. To define the differences in immune reconstitution between DUCB transplantation and HLA-matched unrelated donor (MUD) transplantation, we performed a detailed, prospective analysis of immune reconstitution in 42 DUCB recipients and 102 filgrastim-mobilized unrelated peripheral blood stem cell recipients. Reconstitution of CD3 T cells was significantly delayed in the DUCB cohort compared with the MUD cohort for 1–6 months post-transplantation (p<0.001), including naive (CD45RO−) and memory (CD45RO+) CD4 T cells, regulatory (CD4CD25) T cells, and CD8 T cells. In contrast, CD19 B cells recovered more rapidly in the DUCB cohort and numbers remained significantly greater from 3–24 months after transplantation (p=0.001). CD56CD16 natural killer (NK) cells also recovered more rapidly in DUCB recipients and remained significantly greater from 1–24 months after transplantation. B cell activating factor (BAFF) levels were higher in the DUCB cohort at 1 month (p<0.001), were similar in both cohorts at 3 and 6 months, and were lower in the DUCB cohort at 12 months (p=0.002). BAFF/CD19 B cell ratios were lower in the DUCB cohort at 3 (p=0.045), 6 (p=0.02), and 12 months (p=0.002) after transplantation. DUCB recipients had more infections within the first 100 days after transplantation (p<0.001), and there was less chronic graft-versus-host disease (cGVHD) (p<0.001), but there were no differences in cumulative incidence of relapse, non-relapse death, progression-free survival or overall survival between the two groups. These results suggest that increased risk of infections is specifically associated with delayed reconstitution of all major T cell subsets, but the increased risk is limited to the first 3 months after DUCB transplantation. There is no increased risk of relapse suggesting that graft-versus-leukemia (GVL) activity is maintained. Early reconstitution of B cells and NK cells may, in part, account for these findings.

Impact of the source of hematopoietic stem cell in unrelated transplants: Comparison between 10/10, 9/10‐HLAmatched donors and cord blood

“…In patients that lack an available matched-related or -unrelated donor (MUD), mismatched-unrelated donors (MMUD), unrelated cord blood (UCB), and haploidentical related donors have emerged as effective alternative stem cell sources. In comparison with transplants from adult donors, UCB transplants offer the advantage of prompt availability for many recipients and a decreased risk of graft-versus-host disease (GVHD) [2,3], but such transplants are associated with a slower hematological and immune recovery, leading to a higher risk of infection [4,5]. Mismatched-unrelated donor transplants are associated in some studies with a lower risk of relapse, but a higher risk of GVHD [6,7], while haploidentical HSCT may be complicated by a high risk of relapse and delayed immune recovery [8][9][10].…”

T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor

“…These data suggest similar survival outcomes for the two approaches although the lower incidence of severe acute and chronic GVHD following Haplo-post-HCT-CY may result in an improved quality of life. DUCBT is associated with delayed recovery of T-cell subsets and impaired thymopoiesis when compared with conventional donor transplantation 28,29 and is associated with higher rates of infection in the early posttransplant period. 28,29 Consistent with this is the finding that while EBV-associated PTLD is uncommon following conventional donor transplantation, 30 it is relatively common following DUCBT.…”

“…DUCBT is associated with delayed recovery of T-cell subsets and impaired thymopoiesis when compared with conventional donor transplantation 28,29 and is associated with higher rates of infection in the early posttransplant period. 28,29 Consistent with this is the finding that while EBV-associated PTLD is uncommon following conventional donor transplantation, 30 it is relatively common following DUCBT. 31,32 In contrast, immune recovery following Haplo-post-HCT-CY is more robust resulting in low rates of infection-related mortality and PTLD which appear to be significantly lower than that seen following DUCBT.…”

“…However, until that study is completed, the evidence hitherto available suggests that Haplo-post-HCT-CY may be associated with superior rates of platelet recovery, NRM, severe acute and chronic GVHD and infection-related mortality than DUCBT. 20,23,[27][28][29][33][34][35] In the parallel phase II studies conducted by the BMT-CTN, DUCBT was associated with a somewhat lower incidence of relapse than Haplo-post-HCT-CY (31% vs 45%). However, relapse risk is very subject to selection bias (for example, the Haplo-post-HCT-CY study included more patients with advanced leukemias) and can only be adequately assessed in the context of a large randomized phase III comparison.…”

Tuberculosis in umbilical cord blood transplant recipients: clinical characteristics and challenges

“…1,2 Although Mycobacterium tuberculosis (TB) infection is uncommon in UCBT recipients, few available reports [3][4][5] suggest a more severe clinical course as compared with the TB infections in auto-and allo-SCT recipients. [6][7][8] Here, we report a case of TB following UCBT and discuss its clinical characteristics and challenges.…”