Late thymic deficiency after HLA-haploidentical hematopoietic stem cell transplantation for severe combined immunodeficiency Markus J. Ege, MD, Catharina.

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Late thymic deficiency after HLA-haploidentical hematopoietic stem cell transplantation for severe combined immunodeficiency Markus J. Ege, MD, Catharina Schuetz, MD, Eva-Maria Jacobsen, PhD, Susanna M. Müller-Langer, MD, Ingrid Furlan, MD, Mehtap Sirin, MD, Ulrich Pannicke, PhD, Klaus Schwarz, MD, Klaus-Michael Debatin, MD, Manfred Hönig, MD, Ansgar Schulz, MD, Wilhelm Friedrich, MD Journal of Allergy and Clinical Immunology Volume 143, Issue 4, Pages 1623-1626.e13 (April 2019) DOI: 10.1016/j.jaci.2018.11.027 Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Long-term immune reconstitution. Long-term immune reconstitution data for 63 conditioned and 25 unconditioned individuals; in 3 of these patients data on myeloid engraftment were not available. The Kaplan-Meier estimates refer to counts of CD3+, CD4+, CD4+CD45RA+, and CD8+ T cells (and not to survival) starting at 2 years posttransplantation. An event was defined as a drop in cell counts below age-matched thresholds, that is, 1000/μL for CD3+, 500/μL for CD4+, 100/μL for CD4+CD45RA+, and 300/μL for CD8+ T cells. In addition, the definition of an event required at least 2 consecutive measurements below the threshold. Censoring by loss to follow-up (n = 6), death (n = 4), or end of follow-up in 2013 is marked by ticks. Patients were stratified according to conditioning status (left panel) and presence/absence of myeloid engraftment (right panel). Log-rank test P values are given for each panel (lower left corner). Journal of Allergy and Clinical Immunology 2019 143, 1623-1626.e13DOI: (10.1016/j.jaci.2018.11.027) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Patient flow. Patient flow illustrating the HSCT history of 129 patients with SCID undergoing HLA-haploidentical HSCT without and with conditioning. Following HSCT without conditioning, 7 of 10 patients with graft failure were retransplanted with conditioning and were consequently reclassified as transplanted with conditioning. Journal of Allergy and Clinical Immunology 2019 143, 1623-1626.e13DOI: (10.1016/j.jaci.2018.11.027) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Use of myelosuppressive conditioning since 1985 in relation to introduction of peripheral blood stem cells. Until 1995, as marked by the dotted line, patients received T-cell–depleted bone marrow to prevent GvHD by using soybean agglutination and sheep-red-blood-cell rosette formation.E3 Thereafter, we used G-CSF–mobilized, positively-selected CD34+ peripheral blood stem cells.E4 No further prophylaxis of GvHD was used except in patients with symptomatic GvHD induced by maternofetal transfusion. Journal of Allergy and Clinical Immunology 2019 143, 1623-1626.e13DOI: (10.1016/j.jaci.2018.11.027) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Survival after HLA-haploidenical HSCT in 129 patients with SCID. The upper panel stratifies the entire population (n = 129) for transplantation without and with conditioning. The medium panel stratifies conditioned patients (n = 88) for intensity of conditioning using busulfan at a lower dose (8 mg/kg total dose orally) and a higher dose (16 mg/kg orally or 12.5 mg intravenously). The lower panel stratifies conditioned patients (n = 88) for the time period when HSCT was performed, which until 1995 was with T-cell–depleted marrow and since 1995 with selected blood CD34+ cells. Journal of Allergy and Clinical Immunology 2019 143, 1623-1626.e13DOI: (10.1016/j.jaci.2018.11.027) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Relation of intensity of conditioning and donor myeloid chimerism. Absolute numbers of patients per group are given. The P value is derived from a chi-square test over the two 3-stage variables. Low-intensity conditioning was with busulfan at 8 mg/kg and intensive conditioning with busulfan at 16 mg/kg orally or 12.5 mg/kg intravenously. Journal of Allergy and Clinical Immunology 2019 143, 1623-1626.e13DOI: (10.1016/j.jaci.2018.11.027) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Number of individuals and follow-up time. Journal of Allergy and Clinical Immunology 2019 143, 1623-1626.e13DOI: (10.1016/j.jaci.2018.11.027) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 Illustration of T-cell Vβ chain diversity in CD8+ and CD4+ subpopulations. Boxplots compare the Shannon index of Vβ diversity between healthy individuals and patients with SCID undergoing HSCT in the absence or presence of conditioning. Groups are compared by ANOVA. Patients were studied at a mean of 20.6 years (range, 10.1-34.2) after HSCT. Journal of Allergy and Clinical Immunology 2019 143, 1623-1626.e13DOI: (10.1016/j.jaci.2018.11.027) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions