title: A low CD34+ cell dose results in higher mortality and poorer survival after blood or marrow stem cell transplantation from HLA-identical siblings: should 2 x 10(6) CD34+ cells/kg be considered the minimum threshold?
abstract: We studied the effect of the CD34+ cell dose on transplant-related mortality (TRM) and survival in 39 patients randomized to receive lenograstim-mobilized PBSCT (n = 20) or BMT (n = 19) from HLA-identical siblings. Both marrow and blood were harvested, and one infused in a double-blind fashion. The median nucleated (7.0 vs 3.2 x 10(8)/kg; P < 0.0001), CD34+ (3.7 vs 1.5 x 10(6)/kg; P = 0.002), CFU-GM (42 vs 19 x 10(4)/kg; P = 0.002), and CD3+ (1.9 vs 0.3 x 10(8)/kg; P < 0.0001) cell doses with PBSCT were higher. Thirteen patients (6 BMT and 7 PBSCT) experienced TRM at 15-733 days (median 57); 10 of 20 receiving <2 x 10(6) CD34+ cells/kg compared with three of 19 receiving > or =2. Eight of 20 patients receiving <2 x 10(6) CD34+ cells/kg are alive compared with 14 of 19 receiving > or =2. In Cox analysis, CD34+ cell dose > or =2 x 10(6)/kg was associated with lower TRM (RR 0.2, P = 0.01), and higher overall (RR 3.7, P = 0.01) and event-free (RR 3.2, P = 0.02) survival. Other cell populations and the source of stem cells did not affect TRM or survival. We conclude that 2 x 10(6) CD34+ cells/kg may be the ideal minimum cell dose for allogeneic transplantation although lower doses do not preclude successful therapy. Since the likelihood of obtaining this threshold CD34+ cell number is significantly greater from blood than marrow, PBSCT may be preferable to marrow for allografts from HLA-identical siblings.
authors.affiliation: Leukaemia Unit, Royal Marsden Hospital, Surrey, UK.
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.forename: R
authors.initials: R
authors.lastname: Powles
authors.forename: J
authors.initials: J
authors.lastname: Treleaven
authors.forename: S
authors.initials: S
authors.lastname: Kulkarni
authors.forename: B
authors.initials: B
authors.lastname: Sirohi
authors.forename: C
authors.initials: C
authors.lastname: Horton
authors.forename: B
authors.initials: B
authors.lastname: Millar
authors.forename: V
authors.initials: V
authors.lastname: Shepherd
authors.forename: D
authors.initials: D
authors.lastname: Tait
authors.forename: R
authors.initials: R
authors.lastname: Saso
authors.forename: A
authors.initials: A
authors.lastname: Rowland
authors.forename: S
authors.initials: S
authors.lastname: Long
authors.forename: J
authors.initials: J
authors.lastname: Mehta
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation / Q000401:mortality*; D017252:CD3 Complex / Q000097:blood; D002452:Cell Count; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009679:Nuclear Family; D015996:Survival Rate; D014184:Transplantation, Homologous / Q000401:mortality; D014185:Transplantation, Isogeneic
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex