title: Impact of graft cell dose on transplant outcomes following unrelated donor allogeneic peripheral blood stem cell transplantation: higher CD34+ cell doses are associated with decreased relapse rates.
abstract: Peripheral blood stem cells (PBSC) have been increasingly used in the matched unrelated donor (MUD) transplant setting, but the impact of CD34(+) cell dose on outcomes in this setting have not been well characterized. We analyzed 181 consecutive patients who underwent MUD-PBSC transplantation at the City of Hope between August 2000 to December 2004. Patients were conditioned with either full-intensity regimen or reduced-intensity regimen. There was a significant inverse relationship between higher CD34(+) cell dose and faster neutrophil engraftment (r = -0.16, P = .035). By univariate analysis, a CD34(+) cell dose > or =4.2 x 10(6)/kg (above the lowest quartile) was associated with significantly lower relapse risk (hazard ratio [HR] = 0.67, P = .0126), with a trend for corresponding improvement for disease-free survival (HR = 0.84, P = .12) but not overall survival (HR = 0.91, P = .46). The impact of the CD34(+) cell dose remained significant in multivariate analysis. The higher CD34(+) cell dose was significantly associated with faster recovery of absolute lymphocyte counts on day +30 posttransplant. Subset analysis demonstrated that the higher CD34(+) cell dose was associated with (1) greater reduction in relapse in myeloid malignancies than that in lymphoid malignancies, (2) greater reduction in reduced-intensity conditioning than in full-intensity conditioning, (3) greater reduction in relapse when there is a inhibitory killer-cell immunoglobulin-like receptor ligand (iKIRL)-mismatch in the gravft-versus-host (GVH) direction, and (4) greater reduction in relapse when there is a lack of iKIRL, suggesting that the protective effect of CD34(+) cell dose against relapse may be immune-mediated, possibly through NK cell recovery.
authors.affiliation: Division of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California 91010-3000, USA. makamura@coh.org
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.forename: Nademanee
authors.initials: N
authors.lastname: Auayporn
authors.forename: David D
authors.initials: DD
authors.lastname: Smith
authors.forename: Joycelynne
authors.initials: J
authors.lastname: Palmer
authors.forename: Joel Y
authors.initials: JY
authors.lastname: Sun
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schriber
authors.forename: Vinod
authors.initials: V
authors.lastname: Pullarkat
authors.forename: Pablo
authors.initials: P
authors.lastname: Parker
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Anthony
authors.initials: A
authors.lastname: Stein
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenthal
authors.forename: Shirong
authors.initials: S
authors.lastname: Wang
authors.forename: Chatchada
authors.initials: C
authors.lastname: Karanas
authors.forename: Karl
authors.initials: K
authors.lastname: Gaal
authors.forename: David
authors.initials: D
authors.lastname: Senitzer
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006410:Hematopoiesis; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D012008:Recurrence; D012189:Retrospective Studies; D014019:Tissue Donors / Q000706:statistics & numerical data; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34