Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Institute of Clinical Transfusion Medicine and Cell Therapy (IKTZ), 89081 Heidelberg, Germany.
Cells. 2020 May 15;9(5):1225. doi: 10.3390/cells9051225.
T lymphocyte collection through leukapheresis is an essential step for chimeric antigen receptor T (CAR-T) cell therapy. Timing of apheresis is challenging in heavily pretreated patients who suffer from rapid progressive disease and receive T cell impairing medication.
A total of 75 unstimulated leukaphereses were analyzed including 45 aphereses in patients and 30 in healthy donors. Thereof, 41 adult patients with Non-Hodgkin's lymphoma (85%) or acute lymphoblastic leukemia (15%) underwent leukapheresis for CAR-T cell production.
Sufficient lymphocytes were harvested from all patients even from those with low peripheral lymphocyte counts of 0.18/nL. Only four patients required a second leukapheresis session. Leukapheresis products contained a median of 98 × 10 (9 - 341 × 10) total nucleated cells (TNC) with 38 × 10 (4 - 232 × 10) CD3+ T cells. Leukapheresis products from healthy donors as well as from patients in complete remission were characterized by high TNC and CD3+ T lymphocyte counts. CAR-T cell products could be manufactured for all but one patient.
Sufficient yield of lymphocytes for CAR-T cell production is feasible also for patients with low peripheral blood counts. Up to 12-15 L blood volume should be processed in patients with absolute lymphocyte counts ≤ 1.0/nL.
通过白细胞分离术采集 T 淋巴细胞是嵌合抗原受体 T（CAR-T）细胞治疗的重要步骤。在患有快速进展性疾病并接受 T 细胞损伤药物治疗的大量预处理患者中，白细胞分离术的时机具有挑战性。
共分析了 75 次未刺激的白细胞分离术，包括 45 次患者和 30 次健康供体。其中，41 例非霍奇金淋巴瘤（85%）或急性淋巴细胞白血病（15%）的成年患者接受白细胞分离术以生产 CAR-T 细胞。
即使患者的外周血淋巴细胞计数低至 0.18/nL，也从所有患者中收获了足够的淋巴细胞。仅 4 例患者需要第二次白细胞分离术。白细胞分离术产物中含有中位数为 98×10（9-341×10）个总核细胞（TNC），其中含有 38×10（4-232×10）个 CD3+T 细胞。来自健康供体以及完全缓解患者的白细胞分离术产物具有高 TNC 和 CD3+T 淋巴细胞计数的特点。除了 1 例患者外，均可以生产 CAR-T 细胞产品。
对于外周血计数较低的患者，也可以实现 CAR-T 细胞生产所需的足够的淋巴细胞产量。对于绝对淋巴细胞计数≤1.0/nL 的患者，应处理 12-15 L 左右的血液量。
