Influence of transplanted dose of CD56+ cells on development of graft-versus-host disease in patients receiving G-CSF-mobilized peripheral blood progenitor cells from HLA-identical sibling donors

Abstract

We investigated effects of variations in the cellular composition of G-CSF-mobilized peripheral blood progenitor cell (G-PBPC) allografts on clinical outcomes of allogeneic PBPC transplantation. We retrospectively analyzed transplanted doses of various immunocompetent cells from 27 HLA-identical sibling donors in relation to engraftment, incidence of graft-versus-host disease (GVHD), and survival. Significant variability was documented in both absolute numbers and relative proportions of CD34+, CD2+, CD3+, CD4(high)+, CD4+25+, CD8(high)+, CD19+, CD56+, and CD56+16+ cells contained in these allografts. Stepwise Cox regression analysis revealed that the CD56+ cell dose was significantly inversely correlated with the incidence of GVHD. Thus, there was a significantly higher incidence of grade II acute GVHD in patients receiving a lower CD56+16+ cell dose (hazard ratio (HR) 0.0090; 95% confidence interval (CI),<0.00001-3.38; P=0.031), a higher incidence of chronic GVHD in those receiving allografts with a lower CD56+16+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.0007; P=0.0035), and a higher incidence of extensive chronic GVHD in those receiving allografts with a lower CD56+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.053; P=0.0083). These results suggest that CD56+ cells in G-PBPC allografts from HLA-identical sibling donors may play an important role in preventing the development of GVHD.

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

“…The role of NK cells and their alloreactivity in allogeneic hematopoietic SCT (allo-HSCT) is currently controversial for different transplant settings. 1,[9][10][11][12][13][14] Our earlier study confirmed the deleterious role of a killer Ig-like receptor (KIR) ligand mismatch in this haploidentical GIAC protocol. 15,16 A further study also showed that the recovery of NK cells is, and can be used as, an indicator of the clinical outcome after unmanipulated haploidentical transplantation.…”

“…9,17 However, no data are currently available on the role of NK dose or its subsets in the grafts after unmanipulated haploidentical transplantation. Yamasaki et al 13 showed earlier that the CD16 þ CD56 þ cell dose is inversely correlated with the incidence of GVHD when they studied 27 patients who received PBSCs from HLAidentical sibling donors, suggesting an important role for NK cells in the development of GVHD. This was confirmed by Kim et al 14 in 61 patients receiving G-CSF-mobilized PBSCs.…”

Graft invariant natural killer T-cell dose predicts risk of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation

“…In general, the reported effects of NK- 8 and B-cell 28 doses are either relatively small or not confirmed in all studies, and this was also the case in our study. Our results are also in agreement with several other reports showing that the dose of T cells, the undisputed and most powerful effectors of aGVHD, does not predict risk of aGVHD.…”

“…7 Because T-cell depletion of the graft is also associated with an increased risk of leukemia relapse and infections, research has also focused on identifying other cellular components of the graft that affect the incidence and severity of aGVHD. Indeed, the effect of the graft content of several immune effectors such as T, NK 8 and more recently B cells 9 as well as of the CD4 ϩ CD25 hi FoxP3 ϩ T regulatory cells (Tregs) 10,11 on the risk of aGVHD has been studied extensively.…”

Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose

“…2,3 Higher CD34 ϩ cell doses have been shown to correlate with more frequent chronic GVHD (cGVHD) following myeloablative AHCT, although several recent studies dispute this prognostic connection. [4][5][6][7] The influence of graft composition on clinical outcomes after reduced-intensity conditioning is less well-characterized. With emphasis shifting from myeloablative chemoradiation toward alloimmune effects of the graft, an understanding of the relationships, if any, between donor graft cell subpopulation contents and various outcomes may be particularly important.…”