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?
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.
Singhal
S
S
Leukaemia Unit, Royal Marsden Hospital, Surrey, UK.
Powles
R
R
Treleaven
J
J
Kulkarni
S
S
Sirohi
B
B
Horton
C
C
Millar
B
B
Shepherd
V
V
Tait
D
D
Saso
R
R
Rowland
A
A
Long
S
S
Mehta
J
J
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
D018952:Antigens, CD34; D017252:CD3 Complex