title: Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose.
abstract: The influence of graft composition on clinical outcomes after reduced-intensity conditioning is not well-characterized. In this report we prospectively enumerated CD34+, CD3+, CD4+, and CD8+ cell doses in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) allografts in 63 patients who received transplants following non-myeloablative conditioning with total body irradiation 200 cGy plus fludarabine as treatment for malignant diseases. Donors were HLA-identical siblings (n = 38) or HLA-matched unrelated individuals (n = 25). By univariate analyses G-PBMC CD8+ T-cell dose in at least the 50th percentile favorably correlated with full donor blood T-cell chimerism (P = .03), freedom from progression (P = .001), and overall survival (P = .01). No G-PBMC cell dose influenced grade II to IV acute or extensive chronic graft-versus-host disease. In multivariate analysis only G-PBMC CD8+ T-cell dose (P = .003; RR = 0.2, 95% CI = 0.1-0.6) was associated with improved freedom from progression. Infusion of low G-PBMC CD8+ T-cell dose for reduced-intensity allografting may adversely affect T-cell engraftment and survival outcome.
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University Schol of Medicine, 300 Pasteur Dr, H3249, MC 5623, Stanford, CA 94305-5623, USA.
authors.forename: Thai M
authors.initials: TM
authors.lastname: Cao
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Ruby M
authors.initials: RM
authors.lastname: Wong
authors.forename: Kevin
authors.initials: K
authors.lastname: Sheehan
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.forename: Keith E
authors.initials: KE
authors.lastname: Stockerl-Goldstein
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Johnston
authors.forename: Monic J
authors.initials: MJ
authors.lastname: Stuart
authors.forename: F Carl
authors.initials: FC
authors.lastname: Grumet
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
authors.forename: Robert
authors.initials: R
authors.lastname: Lowsky
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D018414:CD8-Positive T-Lymphocytes / Q000637:transplantation*; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000528:radiation effects; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy; D019650:Hematopoietic Stem Cell Mobilization; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality*; D011994:Recombinant Proteins; D015996:Survival Rate; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
chemical_list: D015703:Antigens, CD; D019653:Myeloablative Agonists; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014740:Vidarabine; C024352:fludarabine