Impact of Serotherapy on Immune Reconstitution and Survival Outcomes After Stem Cell Transplantations in Children: Thymoglobulin Versus Alemtuzumab Laura.

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Impact of Serotherapy on Immune Reconstitution and Survival Outcomes After Stem Cell Transplantations in Children: Thymoglobulin Versus Alemtuzumab Laura Willemsen, Cornelia M. Jol-van der Zijde, Rick Admiraal, Hein Putter, Anja M. Jansen-Hoogendijk, Monique M. Ostaijen-ten Dam, Juul T. Wijnen, Charlotte van Kesteren, Jacqueline L.M. Waaijer, Arjan C. Lankester, Robbert G.M. Bredius, Maarten J.D. van Tol Biology of Blood and Marrow Transplantation Volume 21, Issue 3, Pages 473-482 (March 2015) DOI: 10.1016/j.bbmt.2014.11.674 Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Recovery of lymphocyte subsets after transplantation. Geometric mean of total T cell (CD3), CD4 T cell subset, CD8 T cell subset, NK, and B cell counts at 1, 2, 3, 6, and 12 months after transplantation of patients who received ATG (black lines) and alemtuzumab (grey dashed lines). The grey shaded areas represent the range of healthy children. Error bars indicate the lower and upper 95% CI of the geometric mean. Months after transplantation are shown on all x-axes. On all y-axes, values represent cells/μL. Subset counts were compared using multivariate linear regression analyses with correction for age, patient sex, conditioning regimen, graft manipulation, diagnosis, graft type, HLA match, CMV serostatus of the patient, and CMV serostatus of the donor. An asterisk indicates a significant difference between ATG and alemtuzumab-treated patients (P < .05). All patients receiving rituximab (MabThera), usually for EBV infections, were excluded from B cell analyses from the moment they received Rituximab. Biology of Blood and Marrow Transplantation 2015 21, 473-482DOI: (10.1016/j.bbmt.2014.11.674) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Naïve and memory/effector T cell counts. Absolute counts of naïve and memory/effector CD4 and CD8 T cell counts 2 months after HSCT of patients who received ATG (dark circles) and alemtuzumab (light grey triangles). Within the CD3/CD4+ and CD3/CD8+ T cell subsets naïve cells were phenotypically defined as CD45RA+CCR7+ and memory/effector cells as CD45RA− and/or CCR7−. The horizontal black lines and error bars indicate geometric mean and its lower and upper 95% CI. Values on y-axes represent cells/μL. Cell counts were compared using multivariate linear regression analyses with correction for age, patient sex, conditioning regimen, graft manipulation, diagnosis, graft type, HLA match, CMV serostatus of the patient, and CMV serostatus of the donor. An asterisk indicates a significant difference between ATG and alemtuzumab-treated patients (P < .05). Biology of Blood and Marrow Transplantation 2015 21, 473-482DOI: (10.1016/j.bbmt.2014.11.674) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Impact of drug exposure on immune recovery. Cumulative incidence of recovery of cell (sub)populations related to length of exposure to (A) ATG and (B) alemtuzumab after HSCT. Recovery was defined as reaching absolute cell counts above .5 × 109/L for neutrophils, above 100/μL for CD3 T cells and monocytes, and above 50/μL for CD4 T cells, CD8 T cells, NK cells, and B cells. Patients were divided in 3 groups based on the length of lympholytic drug exposure: short exposure (black lines), median exposure (grey dashed lines), and long exposure (grey dotted lines). Days after transplantation are shown on all x-axes. Biology of Blood and Marrow Transplantation 2015 21, 473-482DOI: (10.1016/j.bbmt.2014.11.674) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Kaplan-Meier survival curves. Probability of (A) overall survival, (B) EFS, (C) NRM, and (D) relapse (risk of recurrence of malignant disease) after HSCT with ATG (black lines) and alemtuzumab (grey dashed lines) as part of the conditioning regimen. Biology of Blood and Marrow Transplantation 2015 21, 473-482DOI: (10.1016/j.bbmt.2014.11.674) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions