title: Improved immune recovery after transplantation of TCRαβ/CD19-depleted allografts from haploidentical donors in pediatric patients.
abstract: Immune recovery was retrospectively analyzed in a cohort of 41 patients with acute leukemia, myelodysplastic syndrome and nonmalignant diseases, who received αβ T- and B-cell-depleted allografts from haploidentical family donors. Conditioning regimens consisted of fludarabine or clofarabine, thiotepa, melphalan and serotherapy with OKT3 or ATG-Fresenius. Graft manipulation was carried out with anti-TCRαβ and anti-CD19 Abs and immunomagnetic microbeads. The γδ T cells and natural killer cells remained in the grafts. Primary engraftment occurred in 88%, acute GvHD (aGvHD) grades II and III-IV occurred in 10% and 15%, respectively. Immune recovery data were available in 26 patients and comparable after OKT3 (n=7) or ATG-F (n=19). Median time to reach >100 CD3+ cells/μL, >200 CD19+ cells/μL and >200 CD56+ cells/μL for the whole group was 13, 127 and 12.5 days, respectively. Compared with a historical control group of patients with CD34+ selected grafts, significantly higher cell numbers were found for CD3+ at days +30 and +90 (267 vs 27 and 397 vs 163 cells/μL), for CD3+4+ at day +30 (58 vs 11 cells/μL) and for CD56+ at day +14 (622 vs 27 cells/μL). The clinical impact of this accelerated immune recovery will be evaluated in an ongoing prospective multicenter trial.
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: H-M
authors.initials: HM
authors.lastname: Teltschik
authors.affiliation: Children's University Hospital, Medical University of Graz, Graz, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Schwinger
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schlegel
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pfeiffer
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schumm
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: A-M
authors.initials: AM
authors.lastname: Lang
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Lang
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: C P
authors.initials: CP
authors.lastname: Schwarze
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ebinger
authors.affiliation: Children's University Hospital, Medical University of Graz, Graz, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Urban
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
mesh_terms: D000293:Adolescent; D064591:Allografts; D018941:Antigens, CD19; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy; D008212:Lymphocyte Depletion / Q000295:instrumentation*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020127:Recovery of Function / Q000276:immunology*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D018941:Antigens, CD19; D016693:Receptors, Antigen, T-Cell, alpha-beta