The in vivo rituximab effects in B cell malignancies are only partially understood. Here we analyzed in a large chronic lymphocytic leukemia (CLL) cohort (n = 80) the inter-patient variability in CLL cell count reduction within the first 24 h of rituximab administration in vivo, and a phenomenon of blood repopulation by malignant cells after anti-CD20 antibody therapy. Larger CLL cell elimination after rituximab infusion was associated with lower pre-therapy CLL cell counts, higher CD20 levels, and the non-exhausted capacity of complement-dependent cytotoxicity (CDC). The absolute amount of cell-surface CD20 molecules (CD20 density x CLL lymphocytosis) was a predictor for complement exhaustion during therapy. We also describe that a highly variable decrease in CLL cell counts at 5 h (88 %–2%) following rituximab infusion is accompanied in most patients by peripheral blood repopulation with CLL cells at 24 h, and in ∼20 % of patients, this resulted in CLL counts higher than before therapy. We provide evidence that CLL cells recrudescence is linked with i) CDC exhaustion, which leads to the formation of an insufficient amount of membrane attack complexes, likely resulting in temporary retention of surviving rituximab-opsonized cells by the mononuclear-phagocyte system (followed by their release back to blood), and ii) CLL cells regression from immune niches (CXCR4^dimCD5^bright intraclonal subpopulation). Patients with major peripheral blood CLL cell repopulation exhibited a longer time-to-progression after chemoimmunotherapy compared to patients with lower or no repopulation, suggesting chemotherapy vulnerability of CLL cells that repopulate the blood.

仅部分了解 B 细胞恶性肿瘤中的体内利妥昔单抗作用。在这里，我们在一个大型慢性淋巴细胞白血病 (CLL) 队列 (n = 80) 中分析了在体内施用利妥昔单抗的前 24 小时内 CLL 细胞计数减少的患者间变异性，以及抗 CD20 抗体治疗后恶性细胞重新增殖的现象。利妥昔单抗输注后较大的 CLL 细胞消除与较低的治疗前 CLL 细胞计数、较高的 CD20 水平和补体依赖性细胞毒性 (CDC) 的未耗尽能力相关。细胞表面 CD20 分子的绝对量（CD20 密度 x CLL 淋巴细胞增多）是治疗期间补体耗尽的预测指标。我们还描述了大多数患者在输注利妥昔单抗后 5 小时 (88%–2%) 的 CLL 细胞计数显着降低，伴随着 24 小时 CLL 细胞的外周血再增殖，而在约 20% 的患者中，这导致 CLL 计数高于治疗前。我们提供的证据表明 CLL 细胞的复发与 i) CDC 衰竭有关，^暗CD5^明亮的克隆内亚群）。与具有较低或没有再增殖的患者相比，具有主要外周血 CLL 细胞再增殖的患者在化学免疫治疗后表现出更长的进展时间，这表明再增殖血液的 CLL 细胞的化疗易损性。