A comparison of T-, B- and NK-cell reconstitution following conventional or nonmyeloablative conditioning and transplantation with bone marrow or peripheral blood stem cells from human leucocyte antigen identical sibling donors

Abstract

Summary:This retrospective study compares the reconstitution of T, B and NK cells in three groups of patients transplanted for haematological malignancies with grafts from their HLAidentical sibling donors. In all, 15 patients received PBSC after a nonmyeloablative conditioning regimen consisting of fludarabine and 200 cGy TBI, 13 patients received PBSC after myeloablative conditioning and 37 patients received BM after myeloablative conditioning. In the nonmyeloablative group, the NK cells normalised after 1 month, the CD8+ T cells normalised after 3 months, the CD4+ T cells reached near normal values after 9 months and the B cell values were reduced until 12 months after transplant. In the two myeloablative groups, recipients of PBSC had a significantly higher number of CD4+ T cells after 4 months (P ¼ 0.004) and after 12 months (P ¼ 0.001), than recipients of BM. We found no differences in the T cell reconstitution between the two PBSC groups. This was of interest as the recipients of nonmyeloablative conditioning were older (Po0.001) and had a higher occurrence of chronic GVHD (Po0.05) than the recipients of myeloablative conditioning. In contrast, the recipients of nonmyeloablative conditioning had a delayed B cell recovery when compared to the patients who received myeloablative conditioning (P ¼ 0.04). Bone Marrow Transplantation (2003) 32, 65-72. doi:10.1038/sj.bmt.1704084 Keywords: immune reconstitution; nonmyeloablative conditioning regimen; peripheral blood stem cell transplantation Allogeneic haematopoietic stem cell transplantation after nonmyeloablative conditioning is a treatment modality increasingly used for patients with haematological malignancies ineligible for conventional myeloablative BMT because of older age, comorbidity or the high treatmentrelated mortality after conventional BMT in particular diseases. The results of nonmyeloablative stem cell transplantation have so far been promising. 1,2 One advantage of the use of a nonmyeloablative conditioning regimen is the brief granulo-and thrombocytopenia, which allows the procedure to be performed in an outpatient setting. The reconstitution of the T, B and NK cells after stem cell transplantation is however also important for the defence against pathogens, 3 and low counts of CD4+ T cells and of B cells have been associated with an increased risk of infection. 4,5 Thymic function is impaired after conventional haematopoietic stem cell transplantation, and this is partially because of the high-dose radiochemotherapy included in the conditioning regimen. 6 As the thymic activity post-transplant has been shown to be important for the generation of a diverse and efficient T cell response, 7,8 the lower toxicity of a nonmyeloablative conditioning regimen could in theory enhance the T cell reconstitution. In this study, we retrospectively compared the reconstitution of absolute numbers of T, B and NK cells in patients transplanted with PBSC and conditioned with a nonmyeloablative regimen to patients who received conventional myeloablative conditio...

Plasma levels of IL-7 and IL-15 after reduced intensity conditioned allo-SCT and relationship to acute GVHD

“…25 Conversely, we found no significant correlation between IL-15 levels and concurrent T-cell counts. Although both CD8 þ T cells and NK cells are particularly responsive to IL-15, 7,10-12 NK cells recover faster than T cells after HLA-matched RIC-allo-SCT, 12,26,27 which agrees with the negative correlation obtained in this study between IL-15 levels and both NK cell counts, and their downregulated expression of the IL-2/15Rb. Together with declining systemic inflammation, IL-15 consumption by expanding NK cells might explain why systemic levels of the cytokine normalize earlier than those of IL-7.…”

Peripheral T-cell expansion and low infection rate after reduced-intensity conditioning and allogeneic blood stem cell transplantation

“…35,36 CD8 High /CD57 þ T cells arise from peripheral expansion and contribute to the oligoclonal antigen-dependent repertoire, while CD8 Low /CD57 þ are corresponding to NK cells, a cell subset also rapidly reconstituted in our study as usually observed after HSCT. 27 In agreement with previous studies, 20,37,38 we observed rapid NK cell reconstitution, since the median CD3À CD56 þ cell counts were close to the normal values as soon as M þ 1.5.…”

“…In contrast to three studies 20,37,38 reporting B-cell reconstitutions (with similar kinetics as our study, that is, low B-cell counts until M þ 7.5 and normal values reached thereafter, 1 year after transplantation) in a context of early high CD4 T-cell counts, we noticed B-cell reconstitution despite long-lasting low CD4 T-cell counts. Low CD4 (helper) T-cell counts may lead to a weaker T-B cooperation and contribute to the lower extensive cGvHD incidence in our study than in these three studies.…”

“…15,16 Different studies evaluating the impact of the source of graft in the allogeneic myeloablative setting emphasize a faster T-cell recovery using peripheral blood stem cells (PBSC) as compared with bone marrow. [17][18][19][20] We analyzed 20 consecutive patients receiving RIC and unmanipulated allogeneic PBSC transplantation (RIC-PBSCT) and monitored immunophenotypic features of circulating lymphoid contingent and thymic emigrants (TREC (thymic TCR rearrangement excision circle)) up to 3.5 years.…”

Immune reconstitution after allogeneic stem cell transplantation with reduced-intensity conditioning regimens

“…Similar results were reported by other authors in smaller series of patients suggesting that survival of host lymphocytes to RIC regimen significantly contributes to immune recovery in these patients in the early period after transplantation. [28][29][30][31] Morecki et al 30 reported no differences in the number of T cells after RIC-SCT in comparison with MAC-SCT; however, RIC regimen hardly lowered the normal T cell-dependent mitogenic response in the first 3 months after transplant.…”