BACKGROUND Recently, anti-CD38 monoclonal antibody (Mab) therapy has become a focus of attention as an additional/alternative option for many hematological neoplasms including T-cell acute lymphoblastic leukemia (T-ALL). It has been shown that antitumor efficacy of anti-CD38-Mab depends on the level of CD38 expression on tumor cells. Reports on CD38 expression in T-ALL are scarce, and data on the effect of cytotoxic chemotherapy on CD38 expression are limited to very few samples. Moreover, it lacks entirely in refractory disease and in adult T-ALL. We report the flow cytometric evaluation of CD38 expression in T-ALL blasts at diagnosis and the effect of cytotoxic chemotherapy on its expression in measurable residual disease (MRD), refractory disease (MRD≥5%), and relapsed disease in a large cohort of T-ALL. METHODS The study included 347 samples (188 diagnostic, 100 MRD, 24 refractory and 35 relapse samples) from 196 (children: 85; adolescents/adults: 111) patients with T-ALL. CD38-positive blasts percentages (CD38-PBPs) and expression-intensity (mean fluorescent intensity, CD38-MFI) were studied using multicolor flow cytometry (MFC). MFC-based MRD was performed at the end-of-induction (EOI-MRD, day 30-35) and end-of-consolidation (EOC-MRD, day 78-85) subsequent follow-up (SFU-MRD) points. RESULTS Patients were classified into early thymic precursor subtype of T-ALL (ETPALL, 54/188, 28.7%), and non-ETPALL (134/188, 71.3%). Of 188, EOI-MRD assessment was available in 152, EOC-MRD was available in 96 and SFU-MRD was available in 14 patients. CD38 was found positive in 97.9% (184/188) of diagnostic, 88.7% (110/124) MRD (including 24-refractory) and 82.9% (29/35) relapsed samples. Median (95% CI) of CD38-PBPs/MFI in diagnostic, MRD, refractory, and relapsed T-ALL samples were, respectively, 85.9% (82.10%-89.91%)/4.2 (3.88-4.47), 74.0% (58.87%-83.88%)/4.6 (3.67-6.81), 79.6% (65.25%-96.11%)/4.6 (3.33-8.47) and 85.2% (74.48%-93.01%)/5.6 (4.14-8.99). No significant difference was noted in CD38 expression between pediatric versus adult and patients with ETPALL versus non-ETPALL. No change was observed in CD38-MFI between diagnostic versus MRD and diagnostic versus relapsed paired samples. However, we noticed a mild drop in the CD38-PBPs in MRD samples compared with the diagnostic samples (p=0.016). CONCLUSION We report an in-depth analysis of CD38 expression in a large cohort of T-ALL at diagnosis, during chemotherapy, and at relapse. Our data demonstrated that CD38 is robustly expressed in T-ALL blasts with a little effect of cytotoxic chemotherapy making it a potentially effective target for antiCD38-Mab therapy.

中文翻译：

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流式细胞术评估新诊断的T细胞急性淋巴细胞白血病中CD38表达水平以及化疗对其在可测量的残留疾病，难治性疾病和复发性疾病中的表达的影响：对抗CD38免疫疗法的意义。

背景技术近来，抗CD38单克隆抗体（Mab）治疗已成为许多血液肿瘤（包括T细胞急性淋巴细胞白血病（T-ALL））的附加/替代选择，成为人们关注的焦点。已经显示抗CD38-Mab的抗肿瘤功效取决于肿瘤细胞上CD38表达的水平。关于T-ALL中CD38表达的报道很少，并且关于细胞毒性化学疗法对CD38表达的影响的数据仅限于极少数样品。而且，它在难治性疾病和成人T-ALL中完全缺乏。我们报告了T-ALL母细胞CD38表达在诊断时的流式细胞仪评估，以及在可测量的残留疾病（MRD），难治性疾病（MRD≥5％）和大范围复发性疾病中细胞毒性化疗对其表达的影响。高。方法该研究包括来自196例T-ALL患者的347个样本（188个诊断，100个MRD，24个难治性和35个复发样本）。使用多色流式细胞仪（MFC）研究了CD38阳性母细胞百分比（CD38-PBPs）和表达强度（平均荧光强度，CD38-MFI）。在诱导结束（EOI-MRD，第30-35天）和合并终止（EOC-MRD，第78-85天）随后的随访（SFU-MRD）点进行基于MFC的MRD。结果患者分为早期胸腺亚型T-ALL（ETPALL，54 / 188，28.7％）和非ETPALL（134 / 188，71.3％）。在188个患者中，有152个提供了EOI-MRD评估，有96个提供了EOC-MRD，有14个患者提供了SFU-MRD。诊断为88.的97.9％（184/188）CD38呈阳性。7％（110/124）MRD（包括24难治性）和82.9％（29/35）复发的样本。诊断，MRD，难治性和复发性T-ALL样本中CD38-PBP / MFI的中位数（95％CI）分别为85.9％（82.10％-89.91％）/ 4.2（3.88-4.47），74.0％（58.87） ％-83.88％）/ 4.6（3.67-6.81），79.6％（65.25％-96.11％）/ 4.6（3.33-8.47）和85.2％（74.48％-93.01％）/ 5.6（4.14-8.99）。小儿和成人以及ETPALL和非ETPALL患者的CD38表达没有显着差异。诊断与MRD以及诊断与复发配对样品之间的CD3​​8-MFI没有观察到变化。但是，我们注意到与诊断样品相比，MRD样品中的CD38-PBP轻度下降（p = 0.016）。结论我们报告了在诊断，化疗和复发时大量T-ALL队列中CD38表达的深入分析。