title: High frequency of donor chimerism after allogeneic transplantation of CD34+-selected peripheral blood cells.
abstract: Ex vivo T cell depletion of allogeneic grafts is associated with a high (up to 80%) rate of mixed chimerism (MC) posttransplantation. The number of transplanted progenitor cells is an important factor in achieving complete donor chimerism in the T cell depletion setting. Use of granulocyte colony-stimulating factor (G-CSF) peripheral blood allografts allows the administration of large numbers of CD34+ cells. We studied the chimeric status of 13 patients who received allogeneic CD34+-selected peripheral blood progenitor cell transplants (allo-PBPCTs/CD34+) from HLA-identical sibling donors. Patients were conditioned with cyclophosphamide (120 mg/kg) and total-body irradiation (13 Gy in four fractions). Apheresis products were T cell-depleted by the immunoadsorption avidin-biotin method. The median number of CD34+ and CD3+ cells infused was 2.8x10(6)/kg (range 1.9-8.6x10(6)/kg) and 0.4x10(6)/kg (range 0.3-1x10(6)/kg), respectively. Molecular analysis of the engraftment was performed using polymerase chain reaction (PCR) amplification of highly polymorphic short tandem repeat (PCR-STR) sequences in peripheral blood samples. MC was detected in two (15%) of 13 patients. These two patients relapsed at 8 and 10 months after transplant, respectively. The remaining 11 patients showed complete donor chimerism and were in clinical remission after a maximum follow-up period of 24 months (range 6-24 months). These results were compared with those obtained in 10 patients who were treated with T cell-depleted bone marrow transplantation by means of elutriation and who received the same conditioning treatment and similar amounts of CD3+ cells (median 0.45x10(6)/kg; not significant) but a lower number of CD34+ cells (median 0.8x10(6)/kg; p = 0.001). MC was documented in six of 10 patients (60%), which was significantly higher than in the allo-PBPCT/CD34+ group (p = 0.04). We conclude that a high frequency of complete donor chimerism is achieved in patients receiving allo-PBPCT/CD34+ and that this is most likely due to the high number of progenitor cells administered.
authors.affiliation: Department of Hematology and Postgraduate School of Hematology Farreras Valentí, Hospital Clinic, University of Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Briones
authors.forename: A
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: M
authors.initials: M
authors.lastname: Lawler
authors.forename: C
authors.initials: C
authors.lastname: Rozman
authors.forename: N
authors.initials: N
authors.lastname: Gardiner
authors.forename: P
authors.initials: P
authors.lastname: Marín
authors.forename: C
authors.initials: C
authors.lastname: Salgado
authors.forename: P
authors.initials: P
authors.lastname: Féliz
authors.forename: S
authors.initials: S
authors.lastname: McCann
authors.forename: E
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D016238:Cytapheresis / Q000379:methods; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D018952:Antigens, CD34