The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT

Abstract

on behalf of Swiss Blood Stem Cell Transplantation Several T-cell depletion (TCD) techniques are used for haploidentical hematopoietic SCT (HSCT), but direct comparisons are rare. We therefore studied the effect of in vitro TCD with graft engineering (CD34 selection or CD3/CD19 depletion, 74%) or in vivo TCD using alemtuzumab (26%) on outcome, immune reconstitution and infections after haploidentical HSCT. We performed a retrospective multicenter analysis of 72 haploidentical HSCT in Switzerland. Sixty-seven patients (93%) had neutrophil engraftment. The 1-year OS, TRM and relapse incidence were 48 (36-60)%, 20 (11-33)% and 42 (31-57)%, respectively, without differences among the TCD groups. In vivo TCD caused more profound lymphocyte suppression early after HSCT, whereas immune recovery beyond the second month was comparable between the two groups. Despite anti-infective prophylaxis, most patients experienced post-transplant infectious complications (94%). Patients with in vivo TCD had a higher incidence of CMV reactivations (54% vs 28%, P ¼ 0.015), but this did not result in a higher TRM. In conclusion, TCD by graft engineering or alemtuzumab are equally effective for haploidentical HSCT.

Does ex vi vo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients?

“…Graft selection may affect lymphocyte ontogeny and delay immune reconstitution after transplant, as shown in previous studies. 16,17 Indeed, in allogeneic transplants, CD34+ selection delayed the CD4 T-lymphocyte reconstitution process, but the difference disappeared 8 months after transplantation, when compared with non-selected patients under similar conditions. 16 In addition, when comparing haploidentical hematopoietic stem cell transplant outcomes after ex vivo CD34+ selection or in vivo purging (alemtuzumab), the incidence of infections was similar, 17 indicating that both depletion methods are equally immunosuppressive.…”

Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene

“…3,6,7 In this study, however, the early rise in the infused CD3 1 CD19 1 T cells was rapidly followed by recovery of endogenous CD3 1 CD19 2 T cells compared with patients who underwent haplo-HSCT without T-cell add-back at concurrent points posttransplant (Amrolia et al 6 ; Figure 1B). At the time of T-cell infusion, CD3…”

“…Although extensive T-cell removal of the graft effectively prevents GvHD, the process also causes prolonged and profound posttransplant immunodeficiency for a year or more, 3,4 with compromised antiviral immunity. [5][6][7] As a consequence, infectious morbidity and mortality remain high and are a frequent cause of treatment failure. [8][9][10] Other groups and our own have shown that the posttransplant infusion of small numbers of donor T lymphocytes that have been depleted of recipient-reactive T cells can improve immune reconstitution and antiviral immunity.…”

EBMT risk score can predict the outcome of leukaemia after unmanipulated haploidentical blood and marrow transplantation

“…There is no evidence indicating which protocol is better. 36 Ciurea et al 37 compared TCR and TCD haploidentical HSCT and found that TCR protocol had a fast immune recovery. This result is in accordance with our data, 7,38 suggesting that a rapid immune reconstitution may contribute to a superior outcome as reported by Ciurea et al 37 Interestingly, healthrelated quality of life in unmanipulated HBMT at our centre is comparable to that in patients receiving HLA-identical sibling allo-HSCT.…”