title: Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation.
abstract: We analyzed the impact of CD34+ cell dose on the outcome of 86 patients undergoing reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation. The RIC was based on fludarabine 150 mg/m2 and melphalan 140 mg/m2 or busulphan 10 mg/kg. A median of 5.68 x 106 CD34+ cells/kg and 2.86 x 108 CD3+ cells/kg were infused. All patients receiving more than percentile 75 (p75) of CD34+ cells reached complete chimerism in T lymphocytes by days 21 to 28, compared with 44% among those receiving p75 or fewer cells (P =.046). Overall, 30.3% patients developed grade 2 to 4 acute graft-versus-host disease (aGVHD). Among 83 evaluable patients, 55.8% developed chronic GVHD (cGVHD). The dose of CD34+ cells infused did influence the development of cGVHD, with a cumulative incidence of extensive cGVHD of 74% vs 47% (P =.02) among patients receiving more than p75 CD34+ cells vs those receiving p75 or fewer. Projected overall survival (OS) and event-free survival (EFS) at 43 months were 60% and 46%, respectively. Neither the dose of CD34+ cells nor the dose of CD3+ cells infused significantly influenced OS and EFS, although among patients categorized as high-risk, 36% of those receiving p75 or fewer CD34+ cells relapsed or progressed, compared with only 9% among those receiving more than p75 CD34+ cells (P =.07). Among patients receiving p75 or fewer CD34+ cells, 36% of high-risk patients relapsed, compared with 10% of low- and intermediate-risk patients (P =.004), while relapse rates were not significantly different between both subgroups when we infused more than p75 CD34+ cells, thus indicating that infusing high doses of CD34+ cells ameliorates the negative effect of advanced disease status at transplantation. cGVHD was associated with better EFS (63% vs 16% at 43 months for patients with and without cGVHD; P <.0001) and better OS (78% vs 28% for patients with and without cGHVD; P <.001). The number of CD34+ cells infused should be tailored to prevent extensive cGVHD among patients categorized as low-risk, while high-risk patients, in whom the graft-versus-leukemia effect may determine disease outcome, should receive high doses of CD34+ cells.
authors.affiliation: Department of Hematology, Hospital Clinico Universitario, Salamanca, Spain. pesimo@usal.es
authors.forename: Jose A
authors.initials: JA
authors.lastname: Perez-Simon
authors.forename: Maria
authors.initials: M
authors.lastname: Diez-Campelo
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.forename: Consuelo
authors.initials: C
authors.lastname: Canizo
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Albert
authors.initials: A
authors.lastname: Altes
authors.forename: Lourdes
authors.initials: L
authors.lastname: Vazquez
authors.forename: Jordi
authors.initials: J
authors.lastname: Sierra
authors.forename: Jesus F San
authors.initials: JF
authors.lastname: Miguel
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis*; D002452:Cell Count; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D006410:Hematopoiesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000592:standards*; D016019:Survival Analysis; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34