title: Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors.
abstract: Positive selected haematopoietic stem cells are increasingly used for allogeneic transplantation with the CD34 antigen employed in most separation techniques. However, the recently described pentaspan molecule CD133 appears to be a marker of more primitive haematopoietic progenitors. Here we report our experience with a new CD133-based selection method in 10 paediatric patients with matched unrelated (n = 2) or mismatched-related donors (n = 8). These patients received a combination of stem cells (median = 29.3 x 10(6)/kg), selected with either anti-CD34 or anti-CD133 coated microbeads. The proportion of CD133+ selected cells was gradually increased from patient to patient from 10% to 100%. Comparison of CD133+ and CD34+ separation procedures revealed similar purity and recovery of target populations but a lower depletion of T cells by CD133+ selection (3.7 log vs. 4.1 log, P < 0.001). Both separation procedures produced >90% CD34+/CD133+ double positive target cells. Engraftment occurred in all patients (sustained primary, n = 8; after reconditioning, n = 2). No primary acute graft versus host disease (GvHD) >/= grade II or chronic GvHD was observed. The patients showed a rapid platelet recovery (median time to independence from substitution = 13.5 d), whereas T cell regeneration was variable. Five patients are alive with a median follow-up of 10 months. Our data demonstrates the feasibility of CD133+ selection for transplantation from alternative donors and encourages further trials with total CD133+ separated grafts.
authors.affiliation: Children's University Hospital, University of Tuebingen, Tuebingen, Germany. prlang@med.uni-tuebingen.de
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Monika
authors.initials: M
authors.lastname: Führer
authors.forename: Christof
authors.initials: C
authors.lastname: Weinstock
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Selim
authors.initials: S
authors.lastname: Kuci
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Dietrich
authors.initials: D
authors.lastname: Niethammer
authors.forename: Johann
authors.initials: J
authors.lastname: Greil
mesh_terms: D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy; D015703:Antigens, CD; D018952:Antigens, CD34; D002648:Child; D002675:Child, Preschool; D006023:Glycoproteins; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D006402:Hematologic Diseases / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000628:therapy; D008231:Lymphopenia / Q000628:therapy; D010455:Peptides; D010976:Platelet Count; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000628:therapy; D014923:Wiskott-Aldrich Syndrome / Q000628:therapy
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides