R is commonly combined with chemotherapy and has been shown to improve the outcome of patients (pts) with both indolent and aggressive B-NHL. R is increasingly administered prior to PSC mobilization to in vivo purge the PSC product. Some non-randomized, primarily retrospective, studies have suggested that R administration prior to PSC mobilization has no impact on CD34 cell collection but might have other short-term detrimental effects. We conducted a prospective, randomized trial of chemotherapy-based PSC mobilization with or without R. All pts had B-NHL and were eligible for autologous stem cell transplantation (ASCT). Pts were excluded if they had received R within 8 weeks prior to registration. Pts were randomized to receive one of two mobilization regimens (MR): etoposide (VP16) 2 gm/m2 and G-CSF 10 mcg/kg/day alone (VPG) or 3 doses of R 375 mg/m2 at 2 weeks, 1 week, and 1–2 days prior to VP16 2 gm/m2 and G-CSF 10 mcg/kg/day (VPG-R). PSC collection was begun when WBC >1000 and continued in an attempt to collect at least 7 x 106 CD34/kg. The primary endpoint was CD34/kg yield. 76 pts were enrolled. 11 VPG and 10 VPG-R pts were not evaluable: 7 VPG and 4 VPG-R pts never received any MR; 4 VPG and 6 VPG-R dropped out or were removed from the study prior to initiation of the assigned MR. 27 VPG and 28 VPG-R pts received the assigned MR and were evaluable for CD34 collection. The two groups were well balanced for pt and disease characteristics. Five pts [4/27 (14.8%) VPG and 1/28 (3.6%) VPG-R] failed to collect ≥2.0 x 106 CD34/kg (p=.15). There was no statistically significant difference in the number of pheresis days or total CD34 yield between the two MR groups. Compared to the VPG pts, the VPG-R pts tended to collect more CD34/kg during the first two days of pheresis. 50 B-NHL pts (15 follicular, 34 diffuse large B-cell, and 1 other) received the assigned MR (23 VPG and 27 VPG-R), collected ≥2 x 106 CD34/kg, and subsequently received high dose busulfan, VP16, cyclophosphamide and ASCT. There was no significant difference in the number of CD34/kg infused, days until ANC >500 or platelets >20K, length of hospitalization, decrease in 6 week post-ASCT pulmonary diffusion capacity, or 6 week or 6 month (mo) post-ASCT hypogammaglobulinemia. One VPG-R pt developed transient neutropenia 3 mo post-ASCT. During the first 6 mo post-ASCT, fatal pneumonitis occurred in 1 VPG and 2 VPG-R pts, and fatal infections occurred in 1 VPG and 1 VPG-R pts. With a median follow-up among surviving pts of 39 (1–59) mo, there is no significant difference in freedom from progression (FFP), progression-free survival (PFS), or overall survival (OS). We conclude that the administration of R immediately prior to PSC mobilization has no adverse effect on CD34 yield. The two week delay from the last salvage chemotherapy regimen to the administration of VP16 in the VPG-R group has no detrimental impact on disease outcome and may actually enhance PSC collection during the first two days of pheresis. Furthermore, our data suggests that R immediately prior to PSC mobilization has no clinically significant effect on short- or long-term complications. Whether R administration prior to PSC mobilization improves FFP, PFS, or OS awaits longer follow-up and larger studies powered to address this critical issue.