Immune reconstitution after purified autologous and allogeneic blood stem cell transplantation compared with unmanipulated bone marrow transplantation in children

Abstract

(P < 0AE01) compared with the BM group. The numbers of proven bacterial and viral infections were equally distributed between the three groups. In conclusion, recipients of allogeneic highly purified CD34 + PBSC or unmanipulated BM have higher lymphocyte subset counts at 6 months after transplantation than recipients of autologous CD34-selected PBSC. Infection rates and outcome, however, were not significantly different.Keywords: immune reconstitution, transplantation, purified blood stem cells, bone marrow, children. Lang et al, 2004). T-cell depletion of the graft, however, is known to impair T-cell reconstitution in the recipient, causing post-engraftment immunodeficiency and increased non-relapse mortality (Ochs et al, 1995;Davison et al, 2000).The aim of the present prospective study was to analyse and compare laboratory data of immunity in children receiving unmanipulated allogeneic BM or CD34-selected autologous or allogeneic PBSC. Patients and methods Patient characteristicsOver a 7-year period, 61 children were enrolled in this study after informed consent was obtained from parents. Eighteen patients died early after HSCT and could not be evaluated. Seven patients were lost to follow-up. Patients receiving autologous unselected PBSC (n ¼ 2), autologous PBSC + autologous BM (n ¼ 1) and unmanipulated UCB (n ¼ 2) were excluded. The remaining 31 patients (female: n ¼ 9, male: n ¼ 22) were diagnosed with severe aplastic anaemia . These patients underwent a total of 31 single HSCT and were studied with respect to immunological reconstitution. All 31 transplantations were grouped according to the different stem cell source used: autologous CD34-selected PBSC (group 1; n ¼ 10), allogeneic CD34-selected PBSC (group 2; n ¼ 12), and allogeneic unmanipulated BM (group 3; n ¼ 9) for statistical analysis. Transplantation characteristicsTransplantation characteristics are depicted in Table I. As conditioning regimen patients received busulfan-based (n ¼ 13), total body irradiation (TBI)-based (n ¼ 4) or other high dose chemotherapy-based regimens (n ¼ 13). In one patient, a reduced intensity immunoablative conditioning regimen was used. Graft manipulationAutologous PBSC were mobilised and harvested according to treatment protocols used. Allogeneic PBSC were mobilised by subcutaneous injection of granulocyte colony-stimulating factor (G-CSF, 5-10 lg/kg body weight/d) once daily for 5 consecutive days. Allogeneic and autologous PBSC were CD34-selected using the CD34 + Progenitor Cell Isolation Kit (Miltenyi Biotec, Bergisch Gladbach, Germany) applying a magnetic cell separation (MACS) technique using the Clini-MACS sorting device (Miltenyi Biotec) according to the manufacturer's instructions. The purity and recovery of the isolated CD34 + cells and the contamination with T-lymphocytes were assessed by flow cytometry. Autologous PBSC were frozen after dilution with a dimethylsulfoxide (DMSO) containing freezing solution using a computerised nitrogen freezer and stored at )193°C in the liquid phase of nitrogen until tran...

Immune reconstitution after autologous hematopoietic transplantation with Lin−, CD34+, Thy-1lo selected or intact stem cell products

“…Both patient groups had similar hematological and immune recovery [15], although CD4 + CD45RA + cell recovery was delayed in patients receiving the enriched CD34 + cell product. Similar observations have been made in patients receiving allogeneic hematopoietic transplantation using a selected CD34 + PSC or an unmanipulated graft [40][41][42]. Our data support the observation that the infusion of enriched autologous stem cell products causes only marginal effects on immune reconstitution post-transplantation as compared to the infusion of an intact product.…”

A pilot study of reduced toxicity conditioning with BU, fludarabine and alemtuzumab before the allogeneic hematopoietic SCT in children and adolescents

“…31 Also, transplantation of PBSC in children seemed to elicit the fastest reconstitution of CD3 þ , CD4 þ CD3 þ , CD8 þ CD3 þ and naı¨ve T-cells compared with BM or CD34-selected PBSC, which did not differ. 32,33 No significant differences in immune recovery between CD34 selected PBSC vs others were observed in our cohort of patients, presumably because the use of alemtuzumab caused immunosuppression in all patients regardless of stem cell source and manipulation. On the other hand, no significant delay in post-transplant Ig subset levels was observed, which suggests relatively good function of B lymphocytes within the first post-transplant year after BFA conditioning, in spite of their decreased absolute peripheral blood count.…”

Autograft HIV-DNA Load Predicts HIV-1 Peripheral Reservoir After Stem Cell Transplantation for AIDS-Related Lymphoma Patients

“…In these subjects, risks associated with delayed lymphocyte recovery and infection-related mortality after transplantation might be managed by increasing the dose of infused purified CD34 + progenitor cells and by infection surveillance and prevention. 46,47 In conclusion, this study provides evidence that autograft HIV-1 reservoir size influences posttransplant peripheral HIV-1 reservoir size in patients on effective cART. The latter prevents substantial reseeding of the infused HIV-1 reservoir to the reconstituting immune system.…”