Allogeneic peripheral blood stem cell graft composition affects early T‐cell chimaerism and later clinical outcomes after non‐myeloablative conditioning

Abstract

fludarabine or autologous HCT predicted higher early T-cell chimaerism (P ¼ 0AE001), while advanced donor age predicted lower chimaerism (P £ 0AE02). Patients with aggressive diseases were at higher risk for relapse/ disease progression, and shorter progression-free and overall survival (P < 0AE01). These results suggest that the dosing of certain cellular subsets of PBSC products can influence important outcomes post-HCT after nonmyeloablative conditioning.

High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation

“…29 However, one recent study also failed to find a correlation between high CD34 þ cell dose and high incidence of chronic GVHD in patients given related G-PBMC after nonmyeloablative conditioning. 30 The current observations suggested that there is no upper cell dose limit for patients given unrelated G-PBMC after nonmyeloablative conditioning with fludarabine and 2 Gy TBI. 30 When data from all patients were analyzed, there were trends for better PFS and OS with higher cell doses for all cell type variables, and that association was significant for TNC.…”

“…30 The current observations suggested that there is no upper cell dose limit for patients given unrelated G-PBMC after nonmyeloablative conditioning with fludarabine and 2 Gy TBI. 30 When data from all patients were analyzed, there were trends for better PFS and OS with higher cell doses for all cell type variables, and that association was significant for TNC. This observation agreed with previous reports demonstrating better PFS in unrelated recipients given higher nucleated cell doses after myeloablative conditioning.…”

The number of infused CD34+ cells does not influence the incidence of GVHD or the outcome of allogeneic PBSC transplantation, using reduced-intensity conditioning and antithymocyte globulin

“…The authors did not find any effect of CD34 þ or CD3 þ cell dose on incidence of aGVHD, cGVHD and RR. In a similar study, Panse et al 23 analyzed the influence of various cell subsets contained in PBSC grafts, on the outcome for 125 patients with hematological malignancies after allo-PBSC from matched related donors. Conditioning (NST) consisted of low-dose TBI (2 Gy) alone or in combination with fludarabine (90 mg/m 2 ), while for GVHD prophylaxis CYA plus MMF was given to all the patients.…”

Non-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial

“…In support of the latter hypothesis, two retrospective studies failed to demonstrate an association between the numbers of CD8 þ T cells transplanted and acute GVHD incidence. 7,8 However, it should be stressed that none of these studies used CD8 depletion of PBSC, and the median number of CD8 þ T cells infused in the current CD8-depleted group was 2.5-5 times lower than the minimal number of transfused CD8 þ T cells in these studies. 7,8 In contrast to our results, CD8 depletion of the grafts has been associated with decreased incidence of grade II-IV acute GVHD in a randomized study including 38 patients given marrows from HLA-identical siblings following myeloablative conditioning and cyclosporine alone as GVHD prophylaxis (20 versus 80%, Po0.01).…”

“…7,8 However, it should be stressed that none of these studies used CD8 depletion of PBSC, and the median number of CD8 þ T cells infused in the current CD8-depleted group was 2.5-5 times lower than the minimal number of transfused CD8 þ T cells in these studies. 7,8 In contrast to our results, CD8 depletion of the grafts has been associated with decreased incidence of grade II-IV acute GVHD in a randomized study including 38 patients given marrows from HLA-identical siblings following myeloablative conditioning and cyclosporine alone as GVHD prophylaxis (20 versus 80%, Po0.01). 2 Obviously, there were many discrepancies between the two randomized studies, such as the intensity of the conditioning, the stem cell source and the postgrafting immunosuppression, that could all have had an impact on the efficacy of CD8 depletion for preventing acute GVHD.…”