Unstimulated autologous and allogenic mononuclear cell apheresis

Background

Autologous lymphocytes can be used therapeutically for the production of CAR-T cells or other cellular therapeutics. The dose of lymphocytes could be important in this context. We present data on allogeneic and autologous mononuclear cell apheresis (MNC-A) to obtain starting material for CAR-T cells, donor lymphocyte infusions (DLI) or allogeneic lymphocytes for research (RL). We hypothesise that there are differences in cell dynamics between allogeneic and autologous MNC-A.

Methods

All MNC-A procedures between 10/2009 and 04/2023 were extracted from our electronic records (n=1312). MNC-A was performed with the Cobe Spectra or the Spectra Optia. We started with MNC-A for CAR-T-cells in 2019 using exclusively the Spectra Optia cell separator. The absolute lymphocyte count (ALC) was obtained before and after apheresis. Collection efficiency 2 was calculated as follows: CE2=separated total blood volume * CD3+ cell count in peripheral blood /collected CD3+ cells. Data is presented as median with interquartile ranges. A Mann-Whitney test or a Wilcoxon matched pairs test was used to test for significance.

Results

For CAR-T-cell-MNC-A (n=48), ALC was 690/µl (60; 1480/µl) and CD3+ cell count was 432/µl (268; 915/µl) before MNC-A. The total body blood volume was processed (PTBV) 2.0-fold (1.8; 2.1 fold). CE2 for CD3+ cells was 76.9% (67.3; 87.6%). After CAR-T-Cell-MNC-A, ALC decreased to 520/µl (370; 940/µl) (75% (59; 98%)). For all allogeneic MNC-A (DLI and RL, n=1260), ALC was significantly higher than in CAR-T-cell-MNC-A: 1550/µl (1310; 1860/µl) (p= 0.0086) and decreased to 87% (78; 96%). Comparable DLI-MNC-A (n=66) with respect to PTBV (1.9 (1.85; 1.9) fold) were extracted from the database. These matched DLI-MNC-A again showed significantly less reduction in post-MNC-A lymphocytes to 90% (81; 102%) than observed in CAR-T-cell-MNC-A (p= 0.0079).

Conclusion

Lymphodepleted patients had a significantly lower pre apheresis lymphocyte count than healthy donors and showed a significantly reduced capacity to mobilize lymphocytes into blood indicating a severe impairment of the body lymphocyte pool.

Offenlegung Interessenkonflikt:

none