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 mortal ity (TRM) and survival in 39 patients randomized to receive lenograstim-mob ilized PBSCT (n = 20) or BMT (n = 19) from HLA-identical siblings. Both mar row and blood were harvested, and one infused in a double-blind fashion. Th e 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. Th irteen 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 greater than or equal to 2. Eight of 20 patients receiving <2 x 10(6) CD34+ cells/kg are alive compared with 14 of 19 receiving greater t han or equal to 2. In Cox analysis, CD34(+) cell dose greater than or equal to 2 x 10(6)/kg was associated with lower TRM (RR 0.2, P = 0.01), and high er overall (RR 3.7, P = 0.01) and event-free (RR 3.2, P = 0.02) survival, O ther cell populations and the source of stem cells did not affect TRM or su rvival. We conclude that 2 x 10(6) CD34(+) cells/kg may be the ideal minimu m cell dose for allogeneic transplantation although lower doses do not prec lude successful therapy. Since the likelihood of obtaining this threshold C D34(+) cell number is significantly greater from blood than marrow, PBSCT m ay be preferable to marrow for allografts from HLA-identical siblings.