title: The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings.
abstract: This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells depleted of T cells by CD34(+) positive selection (allo-PBT/CD34(+)) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14. 9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34(+) and CD3(+) cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3(+) cells in the inoculum. Twenty-three of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 x 10(6)/kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 x 10(6)/kg (actuarial probability 18% vs 1%, respectively; P =.0001). The actuarial probability of graft failure progressively increased as the number of CD3(+) cells in the graft decreased, which was determined by grouping the number of CD3(+) cells in quartiles (log-rank P =.03; log-rank for trend P =.003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3(+) cells less than or equal to 0.2 x 10(6)/kg (risk ratio = 17; P <.0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio = 4.8; P =.001). From these results it appears that the number of CD3(+) cells in the inoculum-with a threshold of 0.2 x 10(6)/kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34(+) from HLA-identical siblings. In addition, for patients with CML receiving 0.2 x 10(6)/kg or less CD3(+) cells, total body irradiation might be better than busulphan-based regimens.
authors.affiliation: Institute of Hematology and Oncology, Department of Hematology, Hospital Clínic, University of Barcelona, Barcelona, Spain. aurbano@clinic.ub.es
authors.forename: A
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: C
authors.initials: C
authors.lastname: Rozman
authors.forename: P
authors.initials: P
authors.lastname: Pimentel
authors.forename: C
authors.initials: C
authors.lastname: Solano
authors.forename: J
authors.initials: J
authors.lastname: de la Rubia
authors.forename: S
authors.initials: S
authors.lastname: Brunet
authors.forename: J
authors.initials: J
authors.lastname: Pérez-Oteiza
authors.forename: C
authors.initials: C
authors.lastname: Ferrá
authors.forename: J
authors.initials: J
authors.lastname: Zuazu
authors.forename: D
authors.initials: D
authors.lastname: Caballero
authors.forename: A
authors.initials: A
authors.lastname: Carvalhais
authors.forename: J L
authors.initials: JL
authors.lastname: Díez
authors.forename: I
authors.initials: I
authors.lastname: Espigado
authors.forename: C
authors.initials: C
authors.lastname: Martínez
authors.forename: F
authors.initials: F
authors.lastname: Campilho
authors.forename: M A
authors.initials: MA
authors.lastname: Sanz
authors.forename: J
authors.initials: J
authors.lastname: Sierra
authors.forename: J
authors.initials: J
authors.lastname: García-Conde
authors.forename: E
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000206:Actuarial Analysis; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000097:blood*; D001782:Blood Donors; D017252:CD3 Complex / Q000097:blood*; D002452:Cell Count; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000209:etiology* / Q000276:immunology; D019337:Hematologic Neoplasms / Q000150:complications / Q000175:diagnosis / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000592:standards; D006648:Histocompatibility; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000175:diagnosis / Q000628:therapy; D008212:Lymphocyte Depletion / Q000592:standards; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009679:Nuclear Family; D011379:Prognosis; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex