Clinical relevance of NK, NKT, and dendritic cell dose in patients receiving G-CSF-mobilized peripheral blood allogeneic stem cell transplantation

Abstract

To analyze the relationship between the cellular composition of peripheral blood allografts and clinical outcome, we performed a prospective study in 45 adult patients who underwent allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from a histocompatibility leukocyte antigen identical sibling donor for different hematological malignancies. The dose of CD34+, CD3+, CD4+, CD8+, and CD19+ lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, type 1 and type 2 dendritic cells (DC1 and DC2), as well as regulatory T (Treg) lymphocytes was analyzed. All patients were conditioned with busulphan and cyclophosphamide (BuCy2) +/- VP-16 and received a short course of methotrexate and cyclosporin-A as graft-versus-host disease (GVHD) prophylaxis. Acute GVHD (aGVHD) was present in 9 of 43 (21%) patients, and chronic GVHD (cGVHD) developed in 18 of 39 (46%) patients. There was a significantly higher incidence of aGVHD in patients receiving more than 6x10(6)/kg CD34+ cells. In univariate analysis, variables associated with better survival were as follows: a dose of less than 1.5x10(7)/kg NKT cells and less than 1.7x10(6)/kg DC2 for disease-free survival (DFS), and a dose of less than 3x10(7)/kg NK cells, less than 1.5x10(7)/kg NKT cells, less than 3x10(6)/kg DC1, and less than 1.7x10(6)/kg DC2 for overall survival (OS). In the Cox regression analysis, the dose of NKT cells was the only variable associated with better DFS, while the doses of NK, NKT, and CD34+ cells (less than 8x10(6)/kg) were associated with better OS. In conclusion, different circulating cell populations, other than CD34+ cells, are also of relevance in predicting the clinical outcome after allogeneic peripheral blood HSCT.

Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors

“…[23][24][25][26][27][28][29] The NK cell concentration has been found to be an important factor influencing transplant outcome, although there is some controversy over the effect of NK cell dose on aGVHD, cGVHD and survival. 10,13,14,18,30 Our earlier study showed the role of NK cells in this transplant protocol from the perspective of NK cell alloreactivity or, after transplantation, recovery kinetics, 9,15-17 but the role of allograft NK concentration in the clinical outcome for this protocol is unknown.…”

Human Dendritic Cells and Transplant Outcome

“…Significantly higher numbers of pDC of exclusive donor origin were found in patients with cGVHD, whereas the persistence of host DC was observed only in patients free of cGVHD (78). Another clinical study evaluating the relationship between the cellular composition of HSC graft and outcome suggests that a lower number of pDC in the graft (Ͻ1.7ϫ10 6 / kg) results in better disease-free survival and overall survival (79). The nature of interactions between DC subsets and other immune cells in HSC and BM grafts is largely unknown.…”

The relationship between circulating natural killer cells after reduced intensity conditioning hematopoietic stem cell transplantation and relapse-free survival and graft-versus-host disease

“…2,8,9 In animal and human in vivo studies, NK cells have been associated with decreased rates of relapse and GVHD after HLA-haploidentical HSCT. 1,10,11 Studies performed predominantly in animal in vivo and in vitro settings have led to the proposal of various mechanisms of these desirable NK attributes, including actions of the NK cells in the donor graft, 12 naturally occuring KIR ligand incompatibility, 13 and actions by certain activating KIR from the donor graft. 14 We prospectively investigated the potential antitumor effects associated with NK cells and the correlation between post-transplant circulating (in vivo) human mature NK (CD56 + /CD16 + ) reconstitution, and survival, relapse, and GVHD in patients undergoing HLAmatched allogeneic HSCT.…”