Given that pre-apheresis CD34+ cell count (PA-CD34) predicts the apheresis' yield, a minimum of 5 to 20 PA-CD34/μl is required in many institutions to initiate cell collection. The aim of this study was to clarify whether large-volume-apheresis (LVA) could facilitate progenitor cell transplantation in patients with low PA-CD34. Apheresis was initiated in 226 patients, disregarding PA-CD34, at days: +5 in G-CSF, +10 in cyclophosphamide+G-CSF, and +15 to +20 in other chemotherapy+G-CSF mobilization, when leucocytes >2.5 × 109/L. Four times the blood volume was processed. Patients were grouped according to their PA-CD34: ≥10/μl (group-A, n = 143); <10/μl but ≥5/μl (group-B, n = 40) and <5/μl (group-C, n = 43). No differences were found in diagnoses, gender, age, previous treatments or mobilization regimen between groups. Enough CD34+ cells (>1.9 × 106/kg) were obtained in 31 patients (72%) from group-C, although in this group two mobilizations were needed in 20 patients (46.5%), compared to 5 (3.5%) and 1 (2.5%) in groups A and B, respectively (P < 0.01). Evenly three apheresis or more were required in 28 patients (65.1%) from group-C, compared to 8 (5.6%) and 6 (15.0%) in groups A and B, respectively (P < 0.01). In conclusion LVA can facilitate autologous transplantation in poor-mobilizer-patients, low PA-CD34 should not be an inflexible exclusion factor. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc.