Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Department of Hematology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
Blood Adv. 2024 Jul 23;8(14):3760-3770. doi: 10.1182/bloodadvances.2024013089.
Adult T-cell leukemia/lymphoma (ATL) is a poor prognosis hematological malignancy originating from human T-cell leukemia virus 1 (HTLV-1)-infected CD4+ T cells. Flow cytometric plots of CADM1 and CD7 in CD4+ T cells are useful for separating HTLV-1-uninfected T cells and ATL cells. They are indicators of clonal evolution of HTLV-1-infected cells and disease progression of asymptomatic carriers or indolent ATL. However, the impacts of the plots on the clinical course or prognosis of ATL, especially in aggressive ATL, remain unclear. We focused on the N fraction (CD4+ CADM1+ CD7-) reflecting ATL cells and analyzed the flow cytometric profiles and clinical course of 497 samples from 92 HTLV-1-infected patients who were mainly aggressive ATL. The parameters based on N fractions showed significant correlations with known indicators of ATL disease status (soluble interleukin-2 receptor, lactate dehydrogenase, abnormal lymphocytes, etc.) and sensitively reflected the treatment response of aggressive ATL. The parameters based on N fractions significantly stratified the prognosis of aggressive ATL at 4 different time points: before treatment, after 1 course of chemotherapy, at the best response after chemotherapy, and before allogeneic hematopoietic cell transplantation. Even after mogamulizumab administration, which shows potent effects for peripheral blood lesions, the N fraction was still a useful indicator for prognostic estimation. In summary, this report shows that CADM1 vs CD7 plots in CD4+ T cells are useful indicators of the clinical course and prognosis of aggressive ATL. Therefore, this CADM1 and CD7 profile is suggested to be a useful prognostic indicator consistently from HTLV-1 carriers to aggressive ATL.
成人 T 细胞白血病/淋巴瘤（ATL）是一种预后不良的血液系统恶性肿瘤，起源于人类 T 细胞白血病病毒 1（HTLV-1）感染的 CD4+T 细胞。CD4+T 细胞中 CADM1 和 CD7 的流式细胞术图谱可用于分离未感染 HTLV-1 的 T 细胞和 ATL 细胞。它们是 HTLV-1 感染细胞克隆进化和无症状携带者或惰性 ATL 疾病进展的指标。然而，这些图谱对 ATL 临床过程或预后的影响，特别是在侵袭性 ATL 中，仍不清楚。我们专注于反映 ATL 细胞的 N 分数（CD4+CADM1+CD7-），分析了 92 名 HTLV-1 感染患者的 497 个样本的流式细胞术图谱和临床过程，这些患者主要为侵袭性 ATL。基于 N 分数的参数与已知的 ATL 疾病状态指标（可溶性白细胞介素 2 受体、乳酸脱氢酶、异常淋巴细胞等）显著相关，并敏感地反映了侵袭性 ATL 的治疗反应。基于 N 分数的参数在 4 个不同时间点显著分层了侵袭性 ATL 的预后：治疗前、化疗 1 疗程后、化疗最佳反应后和异基因造血细胞移植前。即使在 mogamulizumab 给药后，其对外周血病变显示出强大的效果，N 分数仍然是预后估计的有用指标。总之，本报告表明 CD4+T 细胞中 CADM1 与 CD7 的图谱是侵袭性 ATL 临床过程和预后的有用指标。因此，建议从 HTLV-1 携带者到侵袭性 ATL，始终使用 CADM1 和 CD7 图谱作为有用的预后指标。
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