Immune Reconstitution Kinetics as an Early Predictor for Mortality using Various Hematopoietic Stem Cell Sources in Children

Abstract

The severity of complications of allogeneic hematopoietic stem cell transplantation (HSCT) is governed mainly by the status of immune reconstitution. In this study, we investigated differences in immune reconstitution with different cell sources and the association between the kinetics of immune reconstitution and mortality. Immunophenotyping was performed every 2 weeks in children who had undergone HSCT between 2004 and 2008 at University Medical Center Utrecht. Lymphocyte reconstitution in the first 90 days after HSCT was studied in relation to mortality in 3 HSCT groups: matched sibling bone marrow (BM) recipients (35 patients), unrelated BM recipients (32 patients), and unrelated cord blood recipients (36 patients). The median age of recipients was 5.9 years (range, 0.1-21 years). The nature and speed of T cell, B cell, and natural killer (NK) cell reconstitution were highly dependent on the cell source. In the first 90 days after HSCT, faster B cell and NK cell reconstitution and delayed T cell reconstitution were shown in unrelated cord blood recipients compared with matched sibling BM and unrelated BM recipients. Of the lymphocyte subsets investigated, a large number of NK cells and a more rapid CD4 þ immune reconstitution over time, resulting in sustained higher CD4 þ counts, were the only predictors of a lower mortality risk in all cell sources. The final model showed that during the first 90 days, patients with an area under the CD4 þ cell receiver-operating curve of >4,300 cells/day and no peak in CD4 þ cell counts had the highest likelihood of survival (hazard ratio for mortality, 0.2; 95% confidence interval, 0.06-0.5). Our data indicate that CD4 þ kinetics may be used to identify patients at greatest risk for mortality early after HSCT.

Cord blood transplantation is associated with rapid B-cell neogenesis compared with BM transplantation

“…25 Our data focusing on adult patients showed that T-cell recovery was at least not inferior and appeared to be similar in CB and BM recipients (data not shown). On the other hand, compared with BM and PB, CB was superior for B-cell recovery.…”

Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients

“…For future research, analysis of the relation between cellular reconstitution (for example, CD4 þ count) and IFI might be a valuable contribution to this study. 21 Additional areas of interest are strategies to improve immune-reconstitution and adjuvant immunotherapies to prevent or treat fungal infections. Although the speed of neutrophil engraftment was not significantly associated to the occurrence of IFI, very early engraftment (o14 days) may impact outcomes, as may the use of combined CB/haploidentical transplants.…”

Filgrastim enhances T-cell clearance by antithymocyte globulin exposure after unrelated cord blood transplantation

“…[1][2][3][4][5][6][7] Hence, it is important to understand which factors affect IR and what mechanisms are involved. To our knowledge, we are the first to show IR in context of in vivo active-ATG levels after HCT.…”

“…T-cell immune reconstitution (IR) after HCT is pivotal for disease control and reduces the probability of transplantation-related mortality. [1][2][3][4][5][6][7] To prevent rejection of the graft and graft-versushost disease (GVHD), antithymocyte globulin (ATG; Thymoglobulin, Genzyme) was introduced to conditioning regimens. ATG has a half-life of up to ;30 days 8 and is often still present during the first weeks after HCT.…”

“…It has been shown that this can result in a delayed T-cell IR, [9][10][11][12] which is associated with an increased risk of relapse and viral reactivations and subsequently with lower survival chances. [1][2][3][4][5][6][7] In a recent ATG pharmacokinetic/pharmacodynamic analysis, we found that CD4…”