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.
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.
Nakamura
Ryotaro
R
Division of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California 91010-3000, USA. makamura@coh.org
Auayporn
Nademanee
N
Smith
David D
DD
Palmer
Joycelynne
J
Sun
Joel Y
JY
Schriber
Jeffrey
J
Pullarkat
Vinod
V
Parker
Pablo
P
Rodriguez
Roberto
R
Stein
Anthony
A
Rosenthal
Joseph
J
Wang
Shirong
S
Karanas
Chatchada
C
Gaal
Karl
K
Senitzer
David
D
Forman
Stephen J
SJ
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
D015703:Antigens, CD; D018952:Antigens, CD34