Evaluation of cell collection efficiency in non-mobilized adult donors for autologous chimeric antigen receptor T-cell manufacturing.

BACKGROUND AND OBJECTIVES: Data about collection efficiency 1 (CE1), which takes into account blood cell counts before and after collection, thus providing a more accurate estimate, in the collection of autologous T lymphocytes by apheresis for chimeric antigen receptor (CAR) T-cells remain scarce. We evaluated donor- and procedure-related characteristics that might influence the CE1 of lymphocytes. MATERIALS AND METHODS: We retrospectively reviewed all mononuclear cell (MNC) collections) performed for CAR T-cell manufacturing in our institution from May 2017 to June 2021 in adult patients. Age, gender, weight, total blood volume (TBV), prior haematopoietic cell transplant, diagnosis, days between last treatment and apheresis, pre-collection cell counts, duration of apheresis, TBV processed, vascular access, inlet flow and device type were analysed as potential factors affecting CE1 of lymphocytes. RESULTS: A total of 127 autologous MNC collections were performed on 118 patients diagnosed with acute lymphoblastic leukaemia (n = 53, 45%), non-Hodgkin lymphoma (n = 40, 34%), multiple myeloma (n = 19, 16%), and chronic lymphocytic leukaemia (n = 6, 5%). The median CE1 of lymphocytes was 47% (interquartile range: 32%-65%). In multiple regression analysis, Amicus device was associated with higher CE1 of lymphocytes (p = 0.01) and lower CE1 of platelets (p < 0.01) when compared with Optia device. CONCLUSION: The knowledge of the MNC and lymphocyte CE1 of each apheresis device used to collect cells for CAR T therapy, together with the goal of the number of cells required, is essential to define the volume to be processed and to ensure the success of the collection.

Hyperhemolytic Transfusion Reaction in Non-Hemoglobinopathy Patients and Terminal Complement Pathway Activation: Case Series and Review of the Literature.

Hyperhemolytic transfusion reaction (HHTR) is a severe, life-threatening hemolytic transfusion reaction where hemoglobin value after red blood cell (RBC) transfusion is lower than the pre-transfusion value. When HHTR occurs, mainly in patients with hemoglobinopathy, complement activation up to membrane attack complex (MAC) is strongly suspected. However, our knowledge of HHTR in patients without hemoglobinopathy is limited. In the present study, we retrospectively reviewed patients with the diagnosis of HHTR who were attended at our hospital between 2013 and 2016. We also performed a literature search to identify other reported cases of HHTR. Finally, the role of terminal complement pathway activation in the pathogenesis of HHTR was assessed by exposing endothelial cells in vitro to activated-patient plasma to analyze C5b-9 deposits by immunofluorescence. HHTR was diagnosed in 3 patients according to current criteria. Patients were treated with intravenous immunoglobulins (alone or in conjunction with rituximab and plasma exchange), and all of them recovered successfully. We retrieved from literature search 10 patients without hemoglobinopathy who developed HHTR. A marked increase of C5b-9 (MAC) deposition on endothelial cells (almost 2.5-fold increase versus control, P < .05) was observed with the plasma sample obtained from one of our patients. In conclusion, HHTR was a rare transfusion reaction that occurred in patients without hemoglobinopathy. We add more evidence that complement cascade activation up to MAC might play a role in the pathogenesis of HHTR.