Impact of a low CD34 dose on allogeneic peripheral blood stem cell transplantation Running title: Low CD34 in allogeneic PBSCT

Although the CD34-positive (CD34+) cell dose in allogeneic peripheral blood stem cell transplantation (PBSCT) is considered to be associated with transplant outcomes, a lower acceptable threshold has not been defined. We retrospectively analyzed 2919 adult patients with hematological malignancies who received related PBSCT in Japan between 2001 and 2014. According to the number of CD34+ cells in the graft, we categorized 2494 patients as a standard group (2-5 x 106 cells/kg), 377 as a low group (1-2 × 106 cells/kg), and 48 as a very low group (<1 × 106 cells/kg). Compared to the standard group, the low and very low groups showed delayed neutrophil (93.8%, 89.5%, and 78.3% at day 28, p<0.001) and platelet (69.3%, 53.0%, and 45.5% at day 28, p<0.001) recovery. The 2-year overall survival (OS) was 45.5 %, 45.3 %, and 29.8 %, with inferior survival in the very low group. However, a higher percentage of high-risk patients may account for the inferior survival in the very low group,, and there was no significant difference in OS in a multivariate analysis. There were no differences in relapse, non-relapse mortality, or the development of graft-versus-host disease among the CD34+ groups. In conclusion, allogeneic PBSCT with low CD34+ cell doses of 1-2 × 106 cells/kg gives acceptable results whereas further investigations are needed to evaluate the effects of lower doses of <1×106 cells/kg due to the smaller number and the higher percentage of patients with adverse prognostic factors in this cohort.