The authors examined data from 166 children who received autologous peripheral blood progenitor cell (PBPC) transplantation to ascertain the incidence of early transplant-related mortality (TRM) and the contributing risk factors. Eleven patients (6.6%) (6 boys, 5 girls) died within 180 days following PBPC infusion. The median age was 4 years (range 2-17). The overall probability of TRM was 6.9 +/- 2% at day +180. On univariate analysis, the status of disease at transplantation (complete remission vs. not in complete remission) was identified as the only pretransplant significant predicting factor for TRM (14% of patients who were not in complete remission died within 180 days after PBPC infusion, whereas only 2% of patients in complete remission died) (relative risk [RR] 1.13, 95% confidence interval [CI] 1.01-1.26, P = 0.01). Age, gender, conditioning, and number of CD34+ cells infused were not significantly associated with TRM. In the postinfusion phase, patients who developed multiorgan dysfunction during the neutropenic period, especially when the lung was the first failing organ (RR 16.1, 95% CI 7.16-36.18, P = 0.0001), and those with engraftment syndrome (RR 2.81, 95% CI 1.49-5.24, P = 0.001) had an increased risk for TRM. On multivariate analysis, development of engraftment syndrome was the only significant variable that influenced TRM. In conclusion, the authors found for the first time that engraftment syndrome emerges as the main cause of TRM after autologous PBPC transplantation in children with malignancies.