Novel leukocytapheresis method using highly concentrated sodium citrate solution for the manufacturing of...

For the manufacturing of tisagenlecleucel (tisa-cel) requires the non-mobilized mononuclear cell collection (MNC). CD3⁺ cell collection is performed using the same protocol as autologous peripheral blood stem cell harvest (auto-PBSCH), but this procedure necessitates the same target CD3⁺ cell yields regardless of age or body weight, which may take several days especially in pediatric and small female patients with low white blood cell counts. We previously demonstrated a novel method using highly concentration sodium citrate (HSC), which reduced the need for an anticoagulant (AC) solution and shortened the procedure time in auto-PBSCH. This novel method was expected to offer advantages for smaller patients, prompting us to investigate its application in leukocytapheresis for the manufacturing of tisa-cel. We retrospectively analyzed consecutive leukocytapheresis data obtained using Spectra Optia continuous MNC mode between November 2022 and June 2024 at our institution (n = 9). In six of nine patients, pre-leukocytapheresis CD3⁺ cell counts were less than 500 /μL, but all could obtain the target CD3⁺ cell yields in one day upon processing blood volume adjustment. When we compared patients who had received CD3⁺ cell collection using normal-concentration sodium citrate (NSC) as our previously reported using propensity score-matched pair analysis, the total AC solution volume was significantly lower (1168 vs. 316 mL, p < 0.001) and procedure time was significantly shorter (254 vs. 228 min, p = 0.04) in the HSC group compared to the NSC group. In conclusion, this procedure was also useful for non-mobilized MNC. Our findings warrant validation in a larger patient cohort.