决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Abnormalities by Multicolor Flow Cytometry for Detection of Minimal Residual Disease in Recipients of Allo-HSCT Originating from Donors: A Cohort Study.
通过 MRD 分析检测到的 allo-HSCT 受者异常可能来源于其供者。
目的:异基因造血干细胞移植(allo-HSCT)后的微小残留病(MRD)分析中,异常免疫表型常被视为继发复发或并发症的证据,可能导致过度治疗。本研究使用多色流式细胞术(MFC),旨在确认此类表型异常是否可能源自供者。材料与方法:采用常规双管八色MFC面板,分析3,395名allo-HSCT受者的骨髓标本MRD;同时评估三组无恶性肿瘤患者中异常免疫表型的发生频率。结果:allo-HSCT患者新发异常多态性的发生率为0.088%(3/3,395)。3名完全缓解患者中观察到的异常细胞分别为Fc受体IIIB(Fc RIIIB)基因缺失(CD16⁻中性粒细胞)、CD2⁻CD159a⁻CD159c⁺ NK细胞和单克隆B细胞增多症(MBL)。此外,一名供者在allo-HSCT前检出异常T细胞(CD4⁺CD8⁺)。通过MFC,在3名患者相应供者的外周血中发现了相同异常。无恶性肿瘤人群中,Fc RIIIB缺失发生率为0.2%(11/5,256);CD2缺失且CD159c单阳性的NK细胞为0.05%(1/2,000);单克隆CD4/CD8双阳性T细胞为0.05%(1/2,000);MBL为1.3%(14/1,100)。NK细胞淋巴瘤中,CD2缺失NK细胞频率为1.3%(1/79),CD8弱表达者为14%(11/79)。双管八色MFC面板可识别以下异常:c /c /CD19/CD5/CD20/CD38/CD45/CD56(增加CD10和CD34作为第九和第十色),以及CD16⁺CD56/CD5/CD3/CD7/CD4/CD8/CD2/CD45(增加CD117作为第九色)。结论:allo-HSCT受者MRD分析发现的异常可能源自供者。使用合适的双管八至十色MFC面板筛查供者标本,可能有助于减少误诊。原摘要后附有一段同一研究的土耳其语重复文本,且在源数据中截断;以上译文覆盖了完整英文摘要内容。
OBJECTIVE: In minimal residual disease (MRD) analysis after allogeneic hematopoietic stem cell transplantation (allo-HSCT), abnormal immunophenotyping is commonly considered as evidence of a secondary recurrence or complications, leading to overtreatment. We aimed to confirm whether such phenotypic abnormality might originate from donors using multicolor flow cytometry (MFC). MATERIALS AND METHODS: The MRD of bone marrow specimens of 3395 patients who had received allo-HSCT were analyzed using the conventional two-tube, eight-color MFC panel. The frequencies of abnormal immunophenotypes were also evaluated in three groups of patients without malignancies. RESULTS: The frequency of new abnormal polymorphisms was 0.088% (3/3395) among patients who received allo-HSCT. The abnormal cells seen in three patients in complete remission were Fc receptor IIIB (Fc RIIIB) gene deletion (CD16- neutrophils), CD2-CD159a-CD159c + natural killer (NK) cells, and monoclonal B lymphocytosis (MBL), respectively. In addition, abnormal T-cells (CD4 + CD8 + ) were detected in one donor before allo-HSCT. Identical abnormalities were found in the peripheral blood of the corresponding donors of the three patients via MFC. Among the individuals without malignancies, the incidence of Fc RIIIB deletion was 0.2% (11/5256), that of NK cells with the absence of CD2 and single-positive CD159c was 0.05% (1/2000), that of monoclonal CD4/CD8 double-positive T-cells was 0.05% (1/2000), and that of MBL was 1.3% (14/1100). The frequency of NK cells with the absence of CD2 was 1.3% (1/79) and with CD8 dim was 14% (11/79) in NK cell lymphoma. The following abnormalities could be identified by the two-tube, eight-color MFC panel: c /c /CD19/CD5/CD20/ CD38/CD45/CD56 (adding CD10 and CD34 as the ninth and tenth colors) and CD16 + CD56/CD5/CD3/CD7/CD4/CD8/CD2/CD45 (adding CD117 as the ninth color). CONCLUSION: Abnormalities in recipients of allo-HSCT detected by MRD analysis may originate from their donors. Screening of donor specimens with a suitable two-tube, eight- to ten-color MFC panel may be a promising method for minimizing misdiagnoses. AMAÇ: Allojeneik hematopoetik k k h cre nakli (allo-KHN) sonras minimal kal nt hastal k (MKH) analizinde anormal imm nofenotiplendirme s kl kla sekonder rek rrensin ya da komplikasyonlar n kan t d r, neticede fazla tedaviye yol a ar. Bu tarz fenotipik anormalliklerin ok renkli ak m sitometri (ASM) kullanarak verici k kenli olabilece ini g stermek ve bunu do rulamay hedefledik. GEREÇ VE YÖNTEMLER: Allo-KHN olmu 3395 hastan n kemik ili i rneklerinde konvansiyonel iki t p sekiz renkli ASM paneli ile MKH bak ld . Anormal imm nfenotiplenmenin s kl klar da malignitesi olmayan grup hastada de erlendirildi. BULGULAR: Allo-KHN olan hastalarda yeni anormal polimorfizmlerin s kl %0,088 (3/3395) idi. Tam remisyondaki hastada mevcut anormal h creler s ras yla Fc resept r IIIB (Fc RIIIB) gen delesyonu (CD16 n trofil), CD2CD159aCD159c do al ld r c (NK) h creleri ve monoclonal B lenfositoz (MBL) idi. Ilaveten, bir vericide allo-KHN ncesinde anormal T-h creleri (CD4CD8) tespit edilmi ti. Benzer anormallikler hastan n vericilerinin periferik kanlar nda ASM ile bulunmu tur. Malignitesi olmayan bireylerde Fc RIIIB delesyonu insidans %0,2 (11/5256), CD2 si olmayan NK h creleri ve tek CD159c pozitif olanlar %0,05 (1/2000), monoclonal CD4/CD8 ift pozitif T-h creleri %0,05 (1/2000), MBL %1,3 (14/1100) bulundu. NK h creli lenfomada CD2 negatif NK h creleri s kl %1,3 (1/79) ve CD8 dim olanlar %14 (11/79) idi. S radaki anormallikler ift t p sekiz renkli ASM paneli ile tan mlanm t r: c /c /CD19/CD5/CD20/CD38/CD45/CD56 (CD10 ve CD34 dokuzuncu ve onuncu renk olarak eklenmi tir) ve CD16 + CD56/CD5/CD3/CD7/CD4/CD8/CD2/CD45(CD117 dokuzuncu renk olarak eklenmi tir). SONUÇ: Allo-KHN al c lar nda MKH ile tespit edilen anormallikler vericilerinden kaynaklanabilir. Verici rneklerinin ift t p sekiz-on renkli ASM paneli ile taranmas yanl tan lar en az
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