Table 3.

Transplant outcomes based upon pDC graft content and immune recovery following allogeneic hematopoietic cell transplantation

Outcome	Clinical experience
Graft failure aGvHD	TCRαβ/CD19-depleted haploidentical PBSC grafts (P+G): 4/23 primary graft failures130 MSD PBSC (G): low DC1+ pDC (lin−CD123+) (< 4.97/µL) at engraftment, higher risk131 MUD allografts: low D21 pDC, higher incidence aGvHD126 MRD PBSC (G): low D28 PB pDC (⦤4.5/µL) higher risk aGVHD132 TCRαβ/CD19-depleted haploidentical PBSC grafts (P+G): 2/23 patients with skin Grade I/II only130 Lower post-transplant pDC recovery, higher risk severe aGVHD97 Persistence in host DC chimerism at D100 correlates with aGvHD severity100 GvHD histologic grading correlates with pDC content in intestinal mucosa in GI GvHD patients79
cGvHD	MRD BM: higher pDC cell content, lower risk93,94 TCRαβ/CD19-depleted haploidentical PBSC grafts (P+G): No cGvHD130 MRD PBSC (G): low D28 PB pDC (⦤4.5/µL) higher risk cGVHD132 Patients with cGvHD have elevated PB donor-derived pDCs101
Relapse	MRD BM: higher pDC cell content, higher relapse risk94 MRD PBSC (G): higher graft pDC content (⦥2.3 M/kg), higher risk of relapse98 MSD PBSC (G): low DC1+ pDC (lin−CD123+) (< 4.97/µL) at engraftment, higher risk of relapse131 Low D100 pDC level (< 0.2% PBMC), higher relapse122
Immune recovery	MUD BM: higher CD34 content did not correlate with pDC recovery38 MRD PB (G+GM): lower pDC graft content, faster T-cell recovery37 MUD allografts: low D21 pDC associated with poor prognosis reflected by higher NRM and shorter OS126 pDC (linCD11c−CD123+) content is higher in PBSC grafts and correlates with D30 and D100 PB pDC levels114 Endogenous levels of FL correlated with pDC recovery56 Lower post-transplant pDC recovery, higher risk severe aGVHD97 GvHD impedes PB pDCs recovery96,97,114,116,120–122 Steroids reduce PB pDCs116,119,124,133 Steroids118–120,124 and CSA56,118,125 impair pDC function
Survival	MUD BM: higher pDC content, increased OS due to reduced TRM (fewer GvHD and graft rejection deaths)95 MRD BM: higher pDC cell content, lower EFS94 MRD PBSC (G): higher graft pDC content (⦥2.3 M/kg), lower OS and EFS98 MSD PBSC (G): low DC1+ pDC (lin−CD123+) (< 4.97/µL) at engraftment, higher death131 MUD allografts: low D21 pDC associated with poor prognosis reflected by higher NRM and shorter OS126 RIC MRD PBSC (G): Low D30 PB pDC, higher TRM, lower EFS and OS134 RIC MRD PBSC (G) & BM: D90 ‘High’ PDC recovery profile (≥0.725/µL), higher OS117 Low D100 pDC level (< 0.2% PBMC), lower OS122

Abbreviations: aGvHD = acute GvHD; BM = bone marrow; CSA = cyclosporine; cGvHD = chronic GvHD; EFS= event-free survival FL = flt3 ligand; G = G-CSF; GM = GM-CSF; M = million; MSD = matched sibling donor; MUD = matched unrelated donor; NRM = non-relapse mortality; OS = overall survival; P = plerixafor; PB = peripheral blood; RIC = reduced-intensity conditioning; TRM = transplant-related mortality.