title: A comparison between three graft manipulation methods for haploidentical stem cell transplantation in pediatric patients: preliminary results of a pilot study.
abstract: Transplantation of hematopoietic stem cells from mismatched related donors makes a potential donor available for every child in need of stem cell transplantation. Here, we compare three different graft manipulation methods in patients with leukemias and lymphomas: positive selection of stem cells with either CD34 (n = 39) or CD133-coated magnetic microbeads (n = 14) and a new strategy which depletes T- and B-cells through the use of CD3- and CD19-coated microbeads (n = 11). Median purity of stem cells was comparable after CD34 (+)-selection and CD133 (+)-selection, whereas stem cells were only slightly enriched after CD3 (+)/CD19 (+)-depletion (97.5 %, 93.4 % and 1.02 %). Indirect depletion of T-cells by positive selection resulted in 1 x 10 (4) (median) residual CD3 (+)-cells/kg (0.7-3 x 10 (4)). Patients with CD3/CD19-depleted grafts received 3.2 x 10 (4) (median) (0.7-16 x 10 (4)) residual T-cells/kg. Those grafts also comprised NK-cells (median number: 86 x 10 (6)/kg), dendritic cells and monocytes/granulocytes. Primary engraftment of the stem cell products was comparable after CD34- and CD133-selection (85 and 72 %). In the CD3/CD19 group, 91 % had a primary engraftment. After reconditioning, all patients (64/64) were finally engrafted. Patients with CD34-selected or CD133-selected grafts had similar incidences of a GvHD II-IV (3 and 7 %), whereas a GvHD was slightly increased in patients receiving CD3/CD19-depleted cells (27 %). Reconstitution of CD3 (+) T-cells was faster in the CD3/CD19 group than in the CD34 or CD133 group. These preliminary results indicate, that CD3/CD19-selected grafts may be advantageous regarding engraftment and immunoreconstitution. Since effector cell with potential antileukemic activity are cotransfused, such grafts may be suited in particular for patients with insufficient remission.
authors.affiliation: Children's University Hospital Tübingen, Germany. prlang@med.uni-tuebingen.de
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.forename: M
authors.initials: M
authors.lastname: Schumm
authors.forename: J
authors.initials: J
authors.lastname: Greil
authors.forename: P
authors.initials: P
authors.lastname: Bader
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: I
authors.initials: I
authors.lastname: Müller
authors.forename: T
authors.initials: T
authors.lastname: Feuchtinger
authors.forename: M
authors.initials: M
authors.lastname: Pfeiffer
authors.forename: P-G
authors.initials: PG
authors.lastname: Schlegel
authors.forename: D
authors.initials: D
authors.lastname: Niethammer
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
mesh_terms: D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008212:Lymphocyte Depletion; D008223:Lymphoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008863:Microspheres; D010455:Peptides / Q000276:immunology; D010865:Pilot Projects; D015996:Survival Rate
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018941:Antigens, CD19; D018952:Antigens, CD34; D017252:CD3 Complex; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides