A prospective comparison of immune reconstitution in pediatric recipients of positively selected CD34+ peripheral blood stem cells from unrelated donors vs recipients of unmanipulated bone marrow from related donors

Abstract

Summary:Positively selected CD34 + hematopoietic stem cells from unrelated donors (UD-HSCT) have been successfully transplanted, but little is known about immune reconstitution in this setting. Here we report a prospective comparison of immune reconstitution in recipients of UD-HSCT and of unmanipulated bone marrow from matched sibling donors (MSD-BMT). T-cell reconstitution occurred more than 100 days later in the UD-HSCT than in the MSD-BMT group. The first T cells after UD-HSCT were almost exclusively CD45RO + HLA-DR + , whereas early-emerging T cells after MSD-BMT more frequently expressed CD62L, CD28, and CD25. In both groups, numbers of CD45RA + naive T cells increased after 180 days. After UD-HSCT, the T-cell-receptor (TCR)-repertoire was severely skewed and showed significantly reduced diversity during the first year, but only minor abnormalities were seen after MSD-BMT. TCR-diversity increased simultaneously with the number of naive T cells. In both groups, we observed transient expansions of cd T cells. B cells were reconstituted more rapidly in UD-HSCT than in MSD-BMT recipients, whereas the rapidity of NK-cell reconstitution was similar in the two groups. In summary, T-cell reconstitution was slower after UD-HSCT than after MSD-BMT because of the delayed recovery of early memory-type T cells with reduced TCR-diversity, whereas naive T-, NK-, and B cells were reconstituted similarly in the two groups.

Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+CD3+ count reconstitution is associated with survival

“…Among the factors known to influence immune reconstitution are the stem cell source, the amount of CD34 þ cells and the content of CD3 þ cells in the graft, 3,5,6,[18][19][20][21] the cytomegalovirus status before and after SCT, 6,8,22 the additional application of donor lymphocyte infusion, 9,23,24 the relationship and disparity between donor and recipient, 23,25,26 the age of the patients, 9,21,22 and the development of GvHD. 18,22,27 The influence of the stem cell source on the speed of immunological recovery has been controversial.…”

Flow cytometric CD34+ stem cell enumeration: Lessons from nine years' external quality assessment within the Benelux countries

“…Each send-out, from Spring 1996 to Autumn 2004 was chronologically assigned with a unique number (i.e., [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. In this way, we analyzed any effect of the EQA program on the results of the participants as a function of time.…”

“…HSCs have the capability of homing into the marrow microenvironment and regenerating multi-lineage haematopoiesis in relatively short time (3). Nowadays, many clinical studies have established that transplantation of CD34þ stem cells is a potentially curative therapy for many patients with malignant and nonmalignant haematological diseases (4)(5)(6). Initially, autologous and allogeneic HSC transplants have been performed utilizing bone marrow HSCs (7).…”

In vivo T-cell dynamics during immune reconstitution after hematopoietic stem cell gene therapy in adenosine deaminase severe combined immune deficiency

“…Our data show that the recovery of the peripheral T-cell compartment after HSC GT for ADA-SCID is driven by both naive and memory cells, to an extent comparable to what is observed in our age-matched cohort of patients undergoing allogeneic BMT and in previous reports in pediatric and adult BMT recipients. [13][14][15] Our cohort of pediatric BMT patients was heterogeneous and included only a minority of patients with ADA-SCID. Nevertheless, we did not find statistically significant differences within this cohort by comparing the absolute number of lymphocytes or T-cell subsets counts with respect to conditioning or diagnosis (data not shown; Fig E2).…”

“…12 After BMT, the reconstitution of the peripheral T cells is mainly driven by memory cells, particularly at early follow-up, in both pediatric and adult recipients. [13][14][15] There is limited information on the relative contribution of the different T-cell subsets and the various mechanisms of differentiation during the T-cell pool reconstitution after GT treatment.…”