title: Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults.
abstract: The dose of graft-nucleated cells and CD34(+) haematopoietic progenitor cells are predictors of allogeneic engraftment and survival in umbilical cord blood (UCB) recipients. In this single institution prospective phase II trial, flow cytometric analyses of CD34(+) progenitor and lymphocyte populations in unmodified single unit human leucocyte antigen (HLA)-disparate UCB grafts infused into 31 consecutive adults (median age 41 years, range 20-64) receiving myeloablative conditioning were compared with clinical outcomes. Median infused UCB graft-nucleated cells and CD34(+) dose was 2.2 x 10(7)/kg and 1.2 x 10(5)/kg respectively. Day to absolute neutrophil count >/=0.5 x 10(9)/l with full donor chimerism averaged 27 d (range 12-41). Univariate analyses demonstrated that UCB graft-infused cell doses of CD34(+) (P = 0.015), CD3(+) (P = 0.024) and CD34(+)HLADR(+)CD38(+) progenitors (P = 0.043) correlated with neutrophil engraftment. This same analysis did not demonstrate a correlation between CD34(+) (P = 0.11), CD3(+) (P = 0.28) or CD34(+)HLADR(+)CD38(+) (P = 0.108) cell dose and event-free survival (EFS). High-resolution matching for HLA-class II (DRB1) resulted in improved EFS (P = 0.02) and decreased risk for acute graft-versus-host disease (GVHD) (P = 0.004). Early mortality (prior to post-transplant day +28) occurred in three patients, while 26 patients achieved myeloid engraftment. These results suggest that UCB graft matching at DRB1 is an important risk factor for acute GVHD and survival, while higher UCB graft cell doses of CD34(+), committed CD34(+) progenitors and CD3(+) T cells favourably influence UCB allogeneic engraftment.
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van Heeckeren
authors.forename: Laura R
authors.initials: LR
authors.lastname: Fanning
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Meyerson
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Cooper
authors.forename: William W
authors.initials: WW
authors.lastname: Tse
authors.forename: Tamila L
authors.initials: TL
authors.lastname: Kindwall-Keller
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jaroscak
authors.forename: Marcie R
authors.initials: MR
authors.lastname: Finney
authors.forename: Robert M
authors.initials: RM
authors.lastname: Fox
authors.forename: Luis
authors.initials: L
authors.lastname: Solchaga
authors.forename: Margaret
authors.initials: M
authors.lastname: Forster
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Creger
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Laughlin
mesh_terms: D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006680:HLA Antigens / Q000032:analysis*; D019337:Hematologic Neoplasms / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D006680:HLA Antigens