Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation

Abstract

Immunologic reconstitution after allogeneic hematopoietic cell transplantation is a critical component of successful outcome. Umbilical cord blood (UCB) transplantation in adult recipients is associated with slow and often inadequate immune recovery. We characterized the kinetics and extent of immune recovery in 95 adult recipients after a dual UCB (n = 29) and matched sibling donor (n = 33) or matched unrelated donor (n = 33) transplantation. All patients were treated with myeloablative conditioning. There were no differences in the immune recovery profile of matched sibling donor and matched unrelated donor recipients. Significantly lower levels of CD3+, CD4+, and CD8+ T cells were observed in UCB recipients until 6 months after transplantation. Lower levels of regulatory T cells persisted until 1 year after transplantation. Thymopoiesis as measured by TCR rearrangement excision circle was comparable among all recipients by 6 months after transplantation. In a subset of patients 1 year after transplantation with similar levels of circulating T cells and TCR rearrangement excision circle, there was no difference in TCR diversity. Compared to HLA-identical matched sibling donor and matched unrelated donor adult hematopoietic cell transplantation recipients, quantitative lymphoid recovery in UCB transplantation recipients is slower in the first 3 months, but these differences disappeared by 6 to 12 months after transplantation.

Figure 1

Sequential changes of immune cell populations after transplantation Black line shows matched sibling donor/matched unrelated donor (MSD/MUD) recipients and dotted line shows umbilical cord blood (UCB) recipients. Abbreviations; RTE, recent thymic emigrant; T-reg, regulatory T cell; CTL, cytotoxic T cell; DC, dendritic cells. The median values are shown as dots and the ends of the whiskers indicate the 25% and 75% percentile values. Available median and 5%/95% percentiles of healthy adults are shown in dotted and solid horizontal lines.[44]

Figure 2

Sequential changes in T-cell receptor rearrangement excision DNA circles (TRECs) before and after transplantation

Figure 3

Representative profiles of TCR Vb gene usage in peripheral blood T cells from recipients of matched sibling donor (A), matched unrelated donor (B), umbilical cord blood transplantation (C), and healthy control (D)

Figure 4

Cumulative incidence of grade II-IV (A) and grade III-IV (B) acute GVHD and chronic GVHD (C) after transplantation Black line shows umbilical cord blood (UCB) recipients and dotted line shows matched sibling donor/matched unrelated donor (MSD/MUD) recipients

Figure 4

Cumulative incidence of grade II-IV (A) and grade III-IV (B) acute GVHD and chronic GVHD (C) after transplantation Black line shows umbilical cord blood (UCB) recipients and dotted line shows matched sibling donor/matched unrelated donor (MSD/MUD) recipients

Figure 5

Cumulative incidence of CMV reactivation after transplantation Black line shows umbilical cord blood (UCB) recipients and dotted line shows matched sibling donor/matched unrelated donor (MSD/MUD) recipients

Figure 6

Progression-free survival after transplantation for all consecutive patients undergoing hematopoietic cell transplantation during the study period (A) and patients who survived at least 3 months without death or relapse after transplantation (B; all patients, C; standard-risk patients) Black line shows umbilical cord blood (UCB) recipients, dotted line shows matched sibling donor (MSD) recipients, and gray line shows matched unrelated donor (MUD) recipients.