Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors.
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.
Lang
Peter
P
Children's University Hospital, University of Tuebingen, Tuebingen, Germany. prlang@med.uni-tuebingen.de
Bader
Peter
P
Schumm
Michael
M
Feuchtinger
Tobias
T
Einsele
Hermann
H
Führer
Monika
M
Weinstock
Christof
C
Handgretinger
Rupert
R
Kuci
Selim
S
Martin
David
D
Niethammer
Dietrich
D
Greil
Johann
J
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
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides