We estimated the effect of CD34(+) stem cell dose during peripheral blood stem cell transplantation (PBSCT) in predicting mortality after total body irradiation (TBI). Between 1997 and 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI (12-13.6 Gy) in 8 fractions over 4 days before undergoing PBSCT; 61 patients received TBI with reduced radiation dose to the lung (6-9 Gy). The number of CD34(+) cells transplanted was recorded for all patients. A cubic spline representation for CD34(+) dose within a Cox proportional hazards model was used to model the relationship between the CD34(+) dose and mortality. Median follow-up was 44 months (range, 12-90 months). The CD34(+) cell dose ranged from 2.45 to 15.90 x 10(6) cells/kg (median, 5.15 x 10(6) cells/kg). Risk of mortality decreased with CD34(+) doses between 4-8 x 10(6) cells/kg and then began to increase. For all patients, CD34(+) doses of 5.1-12.9 x 10(6)/kg resulted in at least a doubling of median survival associated with the lowest CD34(+) value. In patients treated with lung dose reduction, a similar range of CD34(+) dose (4.3-10.2 x 10(6) cells/kg) produced at least a 5-fold improvement from the survival associated with the lowest CD34(+) dose; however, the relationship between CD34(+) dose and mortality was not statistically different when analyzed by lung dose reduction. A method for assessing risk of mortality by CD34(+) dose as a continuous variable is presented. Risk of mortality decreased with CD34(+) doses between 4-8 x 10(6) cells/kg and then began to increase.