Reconstitution of Natural Killer Cell Receptor Repertoires after Unmanipulated HLA- Mismatched/Haploidentical Blood and Marrow Transplantation: Analyses.

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Reconstitution of Natural Killer Cell Receptor Repertoires after Unmanipulated HLA- Mismatched/Haploidentical Blood and Marrow Transplantation: Analyses of CD94:NKG2A and Killer Immunoglobulin-Like Receptor Expression and Their Associations with Clinical Outcome Xiang-Yu Zhao, Xiao-Jun Huang, Kai-Yan Liu, Lan-Ping Xu, Dai-Hong Liu Biology of Blood and Marrow Transplantation Volume 13, Issue 6, Pages 734-744 (June 2007) DOI: 10.1016/j.bbmt.2007.02.010 Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Reconstitution kinetics of CD94:NKG2A and KIR expression by NK cells after transplantation. The median, 25% to 75% percentile ranges, and extreme values of the expression of CD94 (A), NKG2A (B), and KIRs on NK cells (C-E) were shown in the box plot (n = 7). The asterisks (*) represent P < .05 compared with the expression levels of the donors. Biology of Blood and Marrow Transplantation 2007 13, 734-744DOI: (10.1016/j.bbmt.2007.02.010) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 NKG2A expression was inversely correlated with CD158b expression after transplantation. The inverse correlation between NKG2A expression and CD158b expression were shown in patients without II-IV aGVHD by day 30 (n = 11) (A), by day 60 (n = 24) (B), by day 120 (n = 20) (C), by day 180 (n = 16) (D), and by 1 year (n = 12) after transplantation (E). Biology of Blood and Marrow Transplantation 2007 13, 734-744DOI: (10.1016/j.bbmt.2007.02.010) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Acute GVHD altered KIR reconstitution after transplantation. Effect of grades 0 -I (open column) versus II-IV (closed column) aGVHD on CD158a (A), CD158b (B), and CD158e reconstitution (C). *P < .05 between patients with grades 0-I (n = 11) and II-IV aGVHD (n = 13), ##P < .01 or #P < .05 compared with the expression levels of the donors. Biology of Blood and Marrow Transplantation 2007 13, 734-744DOI: (10.1016/j.bbmt.2007.02.010) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Doses of T cell subgroups infused were inversely correlated with the levels of CD158a or CD158e expression after transplantation. Inverse correlation between the dose of CD4+ T cells infused and CD158a expression at days 30 (n = 24) and 60 (n = 24) (A, B), or between the dose of CD8+ T cells infused and CD158e expression at days 30 (n = 24) and 60 (n = 24) (C, D). Effect of “high” (filled column, n = 12) versus “low” (open column, n = 12) dose of T cells on CD158a (E), CD158b (F), and CD158e recovery (G). **P < .01or *P < .05 between patients of the “high” and “low” T cell groups; ##P < .01or #P < .05 compared with the expression levels of the donors. Biology of Blood and Marrow Transplantation 2007 13, 734-744DOI: (10.1016/j.bbmt.2007.02.010) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Increased CD94 expression correlated with poor survival. Different levels of CD94 expression on NK cells between patients that died of TRM/relapse (A) (filled column, n = 8) versus those patients alive with CCR (open column, n = 16), or between their respective donor groups. Cumulative incidence estimates of TRM for patients of group A (n = 12) (B) and group B (n = 12), or for patients of group C (n=12) (C) and group D (n = 12); Kaplan-Meier survival estimates LFS for patients of group A and group B (D), or for patients of group C and group D (E). *P < .05 between the black and white column group. #P < .05 compared with the expression levels of the donors. Biology of Blood and Marrow Transplantation 2007 13, 734-744DOI: (10.1016/j.bbmt.2007.02.010) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 Acute GVHD altered NK reconstitution after transplantation. Effect of grades 0 -I (open column) versus II-IV (closed column) aGVHD on the absolute proportion in WBC (TNC%) of overall NK cells (A), of KIR positive or CD94 (B): NKG2A positive NK cells; and on the absolute number in WBC per microliter (Cells/μl) of KIR positive or CD94:NKG2A positive NK cells (C). *P < .05 or **P < .01 between patients with grades 0-I (n = 11) and II-IV aGVHD (n = 13). Biology of Blood and Marrow Transplantation 2007 13, 734-744DOI: (10.1016/j.bbmt.2007.02.010) Copyright © 2007 American Society for Blood and Marrow Transplantation Terms and Conditions