Higher CD34+ and CD3+ Cell Doses in the Graft Promote Long-Term Survival, and Have No Impact on the Incidence of Severe Acute or Chronic Graft-versus-Host.

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Higher CD34+ and CD3+ Cell Doses in the Graft Promote Long-Term Survival, and Have No Impact on the Incidence of Severe Acute or Chronic Graft-versus-Host Disease after In Vivo T Cell-Depleted Unrelated Donor Hematopoietic Stem Cell Transplantation in Children Krzysztof Kałwak, Julita Porwolik, Monika Mielcarek, Ewa Gorczyńska, Joanna Owoc-Lempach, Marek Ussowicz, Agnieszka Dyla, Jakub Musiał, Dominika Paździor, Dominik Turkiewicz, Alicja Chybicka Biology of Blood and Marrow Transplantation Volume 16, Issue 10, Pages 1388-1401 (October 2010) DOI: 10.1016/j.bbmt.2010.04.001 Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Probability of OS and DFS according to stem cell source. DFS and OS are depicted for the PB group (upper lines) and BM group (lower lines). N, number of patients in each arm of the study cohort, P (log-rank). Biology of Blood and Marrow Transplantation 2010 16, 1388-1401DOI: (10.1016/j.bbmt.2010.04.001) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Probability of OS according to infused age-adjusted median dose of CD34+ cells/kg. Dotted and short-dashed lines depict patients younger than 10 years given CD34+ cell dose below and above age-adjusted median (12.13 × 106 CD34+ cells/kg), whereas dashed and solid lines depict patients older than 10 years given CD34+ cell dose above and below age-adjusted median (7.2 × 106 cells/kg). N, number of patients in each arm of the study cohort, P (log-rank). Biology of Blood and Marrow Transplantation 2010 16, 1388-1401DOI: (10.1016/j.bbmt.2010.04.001) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Independent risk factors associated with probability of OS and DFS. (A) Dashed line depicts lower OS in patients grafted with <10 × 106 CD34+ cells/kg, whereas solid line shows better survival in children who are free from the above-mentioned independent risk factor. (B) Dashed line depicts lower probability of DFS in patients with both independent risk factors: CD34+ cell dose per kg <10 × 106 and the graft mismatched at 2 HLA antigens or 3 antigen/alleles, whereas solid line presents patients without the above-mentioned risk factors. RR, relative risk, CI, confidence interval, P (hazard Cox regression model). Biology of Blood and Marrow Transplantation 2010 16, 1388-1401DOI: (10.1016/j.bbmt.2010.04.001) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Incidence of severe aGVHD grade III-IV. (A) Comparison between PB (solid line) and BM recipients (dotted line). (B) Comparison between patients grafted with Q1 (solid line), Q2 (short-dashed line), Q3 (dotted line), and Q4 (long-dashed line); Q, quartile dose of CD34+ cells/kg. (C) Comparison between patients grafted with Q1 (solid line), Q2 (short-dashed line), Q3 (dotted line), and Q4 (long-dashed line); Q, quartile dose of CD3+ cells/kg. N, number of patients in each group of patients; quartiles of CD34+ dose per kg × 106: Q1 <5.33, Q2 5.33-9.72, Q3 9.73-15.42, Q4 >15.42; quartiles of CD3+ dose per kg × 108: Q1 <1.71, Q2 1.71-4.26, Q3 4.27-6.85, Q4 >6.85, P (log-rank, cumulative incidence). Biology of Blood and Marrow Transplantation 2010 16, 1388-1401DOI: (10.1016/j.bbmt.2010.04.001) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Incidence of severe aGVHD grade III-IV, N, number of patients in each arm of the study cohort. (A) Incidence of severe aGVHD according to degree of HLA match, 10/10, full allele match; 9/10, single HLA allele/antigen mismatch; 8/10, 2 HLA allele/antigen mismatches; 7/10, three HLA allele/antigen mismatches. (B) Incidence of severe aGVHD in patients transplanted from donors mismatched (dotted line) at 2 HLA antigens (8/10 ant) or 3 HLA allele/antigens (7/10) versus others, P (log-rank). Biology of Blood and Marrow Transplantation 2010 16, 1388-1401DOI: (10.1016/j.bbmt.2010.04.001) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 Incidence of extensive cGVHD, N, number of patients in each arm of the study cohort. (A) Comparison between PB (solid line) and BM recipients (dotted line). (B) Comparison between patients grafted with ≥10 × 106 CD34+ cells/kg (solid line) and <10 × 106 CD34+ cells/kg (dotted line). (C) Comparison between patients grafted with ≥4 × 108 CD3+ cells/kg (solid line) and <4 × 108 CD3+ cells/kg (dotted line), P (log-rank). Biology of Blood and Marrow Transplantation 2010 16, 1388-1401DOI: (10.1016/j.bbmt.2010.04.001) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions