Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant.

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Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant Diseases Reveals Good Outcomes and That the Risk of Mixed Chimerism Depends on Underlying Disease, Stem Cell Source, and Alemtuzumab Regimen Rebecca A. Marsh, Marepalli B. Rao, Aharon Gefen, Denise Bellman, Parinda A. Mehta, Pooja Khandelwal, Sharat Chandra, Sonata Jodele, Kasiani C. Myers, Michael Grimley, Christopher Dandoy, Javier El-Bietar, Ashish R. Kumar, Tom Leemhuis, Kejian Zhang, Jack J. Bleesing, Michael B. Jordan, Alexandra H. Filipovich, Stella M. Davies Biology of Blood and Marrow Transplantation Volume 21, Issue 8, Pages 1460-1470 (August 2015) DOI: 10.1016/j.bbmt.2015.04.009 Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 (A) Shows cumulative incidence of mixed chimerism in 203 evaluable patients during the first 6 months after HCT. (B) Violin plots showing the distribution of whole blood donor chimerism in all 203 evaluable patients at initial chimerism testing (median, 13 days; range, 4 to 134 days), time of lowest donor chimerism (median among patients with mixed chimerism, 149.5 days; range, 19 to 1804 days), and time of last follow-up (median, 654 days; range, 13 to 3337 days). (C) Violin plots showing the distribution of whole blood donor chimerism just among the 94 patients who developed mixed chimerism at initial chimerism testing (median, 14 days; range, 9 to 35 days), time of lowest donor chimerism (median, 149.5 days; range, 19 to 1804 days), and time of last follow-up (median, 863.5 days; range, 30 to 2968 days). (D) Stacked bar plots of the percentage of patients with >95%, 50% to 94%, 25% to 49%, 5% to 24%, and <5% donor chimerism over time. Of note, patients who experienced loss of graft (0%) before 3 months after HCT are only included in the 1-, 2-, and 3-month time points. Biology of Blood and Marrow Transplantation 2015 21, 1460-1470DOI: (10.1016/j.bbmt.2015.04.009) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Cumulative incidences of mixed chimerism among patients with (A) differing alemtuzumab schedules, (B) HLA match, (C) stem cell source, and (D) underlying diagnosis. Biology of Blood and Marrow Transplantation 2015 21, 1460-1470DOI: (10.1016/j.bbmt.2015.04.009) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Summary flow chart of interventions for mixed chimerism. Biology of Blood and Marrow Transplantation 2015 21, 1460-1470DOI: (10.1016/j.bbmt.2015.04.009) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Cumulative incidence of acute GVHD (A) grades II to IV and (B) grades III and IV in patients with and without mixed chimerism, before any interventions for mixed chimerism. Cumulative incidence of acute GVHD (C) grades II to IV and (D) grades III and IV in patients with and without mixed chimerism including acute GVHD which occurred after interventions for mixed chimerism (wean or withdrawal of immune suppression, with or without subsequent donor lymphocyte infusion and/or hematopoietic stem cell–containing product). Biology of Blood and Marrow Transplantation 2015 21, 1460-1470DOI: (10.1016/j.bbmt.2015.04.009) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Cumulative incidence of overall (A) grades II to IV and (B) grades III and IV acute GVHD among patients with differing donor and recipient HLA-match categories. Biology of Blood and Marrow Transplantation 2015 21, 1460-1470DOI: (10.1016/j.bbmt.2015.04.009) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 Comparisons of event-free survival of patients based on (A) donor, match and relation, HLA. (B) occurrence of grade III and IV acute GVHD, (C) receipt of different alemtuzumab schedules, (D) underlying diagnosis, or (E) age group (oldest age quartile versus the lower 3 quartiles). Biology of Blood and Marrow Transplantation 2015 21, 1460-1470DOI: (10.1016/j.bbmt.2015.04.009) Copyright © 2015 American Society for Blood and Marrow Transplantation Terms and Conditions