Unrelated-Donor PBSC Collection Facilitated by the NMPD, 1999–2005: Efficacy and Toxicities, Serious Unexpected Events, and Outcomes of Standard vs. Large Volume Collections.
Authors: Pulsipher Michael , Kurian S. , Leitman S. F. , Anderlini P. , Haagenson M. , Logan B. , Horowitz M. M. , Confer D. L. 
Published: October 2019

Abstract
Between 1999 and 2005 the NMDP conducted a prospective trial assessing the safety and efficacy of PBSC collection in >5000 healthy unrelated donors. Donors ranged in age from 18–60 and were mobilized with 10 ug/kg/d G-CSF on days 1–5 with collection on day 5 alone or days 5 and 6. 2400 donor collections (1999–2003) were analyzed in detail for efficacy and toxicity and 5334 collections (1999-June 2005) were reviewed for serious unexpected events. 90% of subjects underwent collection using peripheral access, with 10% requiring central catheter placement. Female donors required central access more frequently than males (20% vs 4%, p<0.001). G-CSF induced bone pain peaked on days 4–5 and was present in greater than 80% of donors, although severe bone pain occurred in at most 5% (Table 1). Grade 3–4 CALGB toxicities occurred in 136 donors (6%) and unexpected serious adverse events occurred in 30 (0.6%, Table 2). Median yield of CD34+ cells for the cohort was 27 x 106 cells/L processed (n=1776, range 0.7–236) on day +5 of G-CSF and 24 x 106 cells/L processed (n=1285, range 1–133) on day +6. Median CD34+ cell dose/kg recipient weight collected was 5 x 106/kg (n=1040, range 0.1–110) on day +5 of G-CSF and 3 x 106/kg (n=751, range 0.1–29) on day +6. Inadequate collections were rare with 5% and 6% of donors yielding <2 or ≥2 but <3 x 106 CD34+ cells/kg recipient weight, respectively (n=1001). The risk of toxicity was the same for standard (≤12L), intermediate (>12≤16L), and large (>16L) volume collections. Importantly, as volumes of apheresis in a single day increased, the yield of CD34+ cells/L processed was unchanged (median yield 27, 26, 28, and 29 x 106/L processed for <12L, ≥12<16L, ≥16<20L, ≥20L); day 5 collection, p =0.4). This resulted in similar outcomes measured in CD34 cells/kg recipient weight for large volume single day collections compared to standard volume 2 day collections. Platelet counts fell more with large compared to standard volume apheresis (change in platelets −83 vs −105 x 109/L, p<0.001), however, the drop in platelets over the course of 2 standard volume procedures was greater than a single large volume procedure (−131 vs −107 x 109/L, p<0.001). In summary, this large prospective trial shows that unrelated donor PBSC collection yields adequate CD34+ cell numbers with low, but measurable rates of significant toxicity. Single-day large vs two-day standard volume procedures resulted in similar cell yields without evidence of increased toxicity. With this data, centers can now more appropriately counsel unrelated adult donors regarding risks of PBSC donation. Large volume, single day collection is a safe and effective resource-sparing alternative to standard volume procedures.
Table 2. Unexpected Serious Adverse Events (N=30/5334, 0.6%) Event Nausea, Vomiting, Headache Bleeding/Thrombocytopenia Citrate Toxicity Severe chest/back pain Other: hypotension/ syncope/ rash/ viral illness N 12 3/3 4 3/1 1/1/1/1 Table 1. Acute G-CSF Toxicities G-CSF Day +1 2 +3 +4 +5 +6 *136/2386 donors experienced the following grade 3–4 toxicities: 89 insomnia, 82 headache, 29 fatigue, 19 nausea, 10 vomiting, 10 anorexia, 8 flu symptoms, 2 myalgias, and 1 skin rash. 80 donors had 1 grade 3–4 toxicity, 26 had 2, 13 had 3, 9 had 4, 5 had 5, and 3 had 6. Any Bone Pain (n=2396) 7% 50% 78% 83% 82% 64% Severe Bone Pain (n=2277) 2% <1% 3% 4% 5% 3% Grade 3–4 CALGB Toxicity* (n=2386) <1% <1% 1% 2% 2% 2%