CD19 is frequently targeted for immunotherapy in B cell malignancies, which may result in loss of CD19 expression in leukemic cells as an escape mechanism. Stage 0 hematogones (Hgs) are normal CD19-negative very early B cell precursors that can be potentially mistaken for CD19 negative residual leukemic cells by flow cytometry (FCM) in B cell acute lymphoblastic leukemia (BCP-ALL) cases treated with anti CD19 therapy. Our main objective was to characterize and study the incidence of stage 0 hematogones in follow-up bone marrow samples of pediatric BCP-ALL cases. We analyzed the flow cytometry standard files of 61 pediatric BCP-ALL cases treated with conventional chemotherapy and targeted anti-CD19 therapy, for identifying the residual disease and normal B cell precursors including stage 0 Hgs. A non-CD19 alternate gating strategy was used to isolate the B cells for detecting the residual disease and stage 0 Hgs. The stage 0 Hgs were seen in 95% of marrow samples containing CD19+ Hgs. When compared with controls and posttransplant marrow samples, the fraction of stage 0 Hgs was higher in patients receiving anti CD19 therapy (p = 0.0048), but it was not significant when compared with patients receiving chemotherapy (p = 0.1788). Isolated stage 0 Hgs are found in samples treated with anti-CD19 therapy simulating CD19 negative residual illness. Our findings aid in understanding the stage 0 Hgs and its association with CD19+ Hgs in anti CD19 therapy and conventional chemotherapy. This is crucial as it can be potentially mistaken for residual disease in patients treated with anti CD19 therapy.

中文翻译：

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通过流式细胞术解读儿童 B 型急性淋巴细胞白血病病例随访骨髓样本中的 0 期血红素：抗 CD19 治疗后残留疾病的潜在模仿者

CD19 经常成为 B 细胞恶性肿瘤免疫治疗的目标，这可能导致白血病细胞中 CD19 表达丧失，作为一种逃逸机制。 0 期血红素 (Hgs) 是正常的 CD19 阴性极早期 B 细胞前体，在接受抗 CD19 治疗的 B 细胞急性淋巴细胞白血病 (BCP-ALL) 病例中，通过流式细胞术 (FCM) 检测，可能会被误认为是 CD19 阴性残留白血病细胞。我们的主要目标是表征和研究儿童 BCP-ALL 病例随访骨髓样本中 0 期血红素的发生率。我们分析了61例接受常规化疗和靶向抗CD19治疗的儿童BCP-ALL病例的流式细胞术标准档案，以识别残留病灶和包括0期Hgs在内的正常B细胞​​前体。使用非 CD19 替代门控策略分离 B 细胞以检测残留疾病和 0 期 Hgs。 95% 的含有 CD19+ Hgs 的骨髓样本中可见 0 期 Hgs。与对照组和移植后骨髓样本相比，接受抗 CD19 治疗的患者的 0 期 Hgs 比例较高 ( p  = 0.0048)，但与接受化疗的患者相比并不显着 ( p  = 0.1788)。在使用模拟 CD19 阴性残留疾病的抗 CD19 疗法治疗的样本中发现了孤立的 0 期汞。我们的研究结果有助于了解 0 期 Hgs 及其与抗 CD19 治疗和常规化疗中 CD19+ Hgs 的关系。这一点至关重要，因为它可能会被误认为接受抗 CD19 治疗的患者的残留疾病。