Successful Engraftment of Autologous Peripheral Blood Progenitor Cells Derived from Multiple Collections in Poor Mobilizers by Hyperstimulation with G-CSF.
Authors: Wu YanYun , Proytcheva Maria A. , Medoff Erin , Seropian Stuart , Snyder Edward L. , Krause Diane , Cooper Dennis L. 
Published: April 2020

G-CSF alone or in conjunction with chemotherapy is the most commonly used regimen to mobilize hematopoietic progenitor cells into peripheral blood (PB) for stem cell harvest. However, in about 10–30 % of patients when mobilized with this regimen, their hematopoietic progenitor cells are not effectively mobilized. We have adopted an approach of using higher doses of G-CSF from 16 to 36 ug/kg patient body weight to mobilize hematopoietic progenitor cells in patients that are poorly mobilized. Poor mobilization (PM) is defined as peak pre-apheresis PBCD34 count of &lt; 20 cells/uL, and good mobilization (GM) is defined as peak pre-apheresis PBCD34 count of ≥20 cells/uL in the expected mobilization time frame. In this study, we retrospectively assess our experience using this mobilization approach regarding its efficacy and safety. The success of stem cell transplantation was evaluated based on neutrophil engraftment defined as an ANC (absolute neutrophil count) &gt;500/uL, and platelet engraftment as a platelet count &gt;20,000/uL without platelet transfusions for 2 consecutive days, respectively, as well as day 15 lymphocyte count. Safety of stem cell mobilization, apheresis collection, and stem cell infusion were also evaluated.

The results are shown in the tables below.

Efficacy and safety of stem cell mobilization and collection Groups I (GM + L) II (GM + H) III (PM + L) IV (PM + H) L: low dose G-CSF (5-12 ug/kg); H: high dose G-CSF (15-36 ug/kg). Median (Range); No. (%) No. (patients/collections) 232/485 62/273 10/40 56/290 Peak PBCD34 (/uL) 85 (21-1320) 30 (21-99) 17 (11-20) 13.5 (5-20) CD34 yield (10^6) per recipient Kg wt/apheresis 3.7 (0.4-37.8) 1.2 (0.2-11.1) 1 (0.4-2.7) 0.7 (0.1-2.89) Total CD34 yield (10^6) per recipient kg wt 9.5 (3.2-37.8) 6.1 (3.2-17.9) 4.6 (2.2-7.2) 4.4 (1.08-6.66) GCSF toxicity (Pain, headache, etc) None 230 (47.4%) 161 (59%) 18 (45%) 158 (54.5%) Mild, no pain meds 155 (32%) 80 (29.3%) 18 (45%) 77 (26.6%) Moderate, requiring NSAIDS 49 (10.1%) 23 (8.4%) 1 (2.5%) 31 (10.7%) Severe, requiring Narcotics 51 (10.5%) 9 (3.3 %) 3 (7.5%) 24 (8.3%) Apheresis Toxicity (none) 87.8% 89.4% 85% 89% Apheresis Toxicity (mild to moderate) 12.2% 10.6% 15% 11% Efficacy and safety of stem cell infusion and engraftment Groups I II III IV Median (Range) No. (Patients /Infusions) 232/249 48/54 8/8 32/32 Total CD34 (10^6)/recipient kg wt infused 5.8 (2.5-18.9) 4.7 (2.0-8.8) 4.1 (2.1-5.9) 3.5 (2.4-5.8) Days to ANC of 500 10 (7-16) 10 (7-12) 10 (9-12) 10 (6-12) Days to platelet of 20,000/uL 10 (6-33) 10 (8-30) 13 (8-34) 10 (8-24) Day 15 (+/− 3) lymphocyte count (x 1000/uL) 0.53 (0-2.96) 0.38 (0.01-1.25) 0.43 (0.24-0.75) 0.74 (0.22-3.69) DMSO toxicity (none) 93.6% 77.8% 75% 90.6% DMSO toxicity (yes) 6.4% 22.2% 25% 9.4%

In summary, multiple collections of autologous peripheral blood progenitor cells through hyperstimulation by G-CSF in poor mobilizers is an effective alternative approach for stem cell harvest. This approach results in successful engraftment, and is safe and well tolerated by patients.