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多参数流式细胞术评分的整合提高了原发性骨髓纤维化标准模型提供的预后分层。

Integration of multiparameter flow cytometry score improves prognostic stratification provided by standard models in primary myelofibrosis.

机构信息

CRIMM, Centro di Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera Universitaria Careggi, Dipartimento di Medicina Sperimentale e Clinica, Denothe Excellence Center, Università degli Studi, Florence, Italy.

Centro Diagnostico di Citofluorimetria e Immunoterapia, Azienda Ospedaliera Universitaria Careggi, Dipartimento di Medicina Sperimentale e Clinica, Denothe Excellence Center, Florence, Italy.

出版信息

Am J Hematol. 2022 Jul;97(7):846-855. doi: 10.1002/ajh.26548. Epub 2022 Mar 31.

Abstract

Prognostic modeling in myelofibrosis (MF) has classically pursued the integration of informative clinical and hematological parameters to separate patients' categories with different outcomes. Modern stratification includes also genetic data from karyotype and mutations. However, some poorly standardized variables, as peripheral blood (PB) blast count by morphology, are still included. In this study, we used multiparameter flow cytometry (MFC) with the aim of improving performance of existing scores. We studied 363 MF patients with available MFC files for PB CD34+ cells count determination at diagnosis. We adapted Ogata score to MF context including 2 parameters: absolute CD34+ cells count (/μL) and granulocytes to lymphocytes SSC ratio. A score of 1 was attributed to above-threshold values of each parameter. Accordingly, patients were categorized as MFC (score = 0, 62.0%), MFC (score = 1, 29.5%), and MFC (score = 2, 8.5%). MFC had significantly longer median OS (not reached) compared to MFC (55 months) and MFC (19 months). We integrated MFC into established models as a substitute of morphological PB blasts count. Patients were reclassified according to MFC-enhanced scores, and concordance (C-) indexes were compared. As regards IPSS, C-indexes were 0.67 and 0.74 for standard and MFC-enhanced model, respectively (Z score - 3.82; p = 0.0001). MFC-enhanced MIPSS70+ model in PMF patients yielded a C-index of 0.78, outperforming its standard counterpart (C-index 0.73; Z score - 2.88, p = 0.004). Our data suggest that the incorporation of MFC-derived parameters, easily attainable from standard assay used for CD34+ cells determination, might help to refine the current prognostic stratification models in myelofibrosis.

摘要

骨髓纤维化(MF)的预后建模经典地追求整合有意义的临床和血液学参数,以将具有不同结局的患者进行分类。现代分层还包括来自核型和突变的遗传数据。然而,一些标准化程度较差的变量,如形态学上的外周血(PB)原始细胞计数,仍包括在内。在这项研究中,我们使用多参数流式细胞术(MFC)来提高现有评分的性能。我们研究了 363 名 MF 患者,这些患者在诊断时具有可用的 MFC 文件,用于确定 PB CD34+细胞计数。我们将 Ogata 评分改编为 MF 背景,包括 2 个参数:绝对 CD34+细胞计数(/μL)和粒细胞与淋巴细胞 SSC 比值。每个参数的阈值以上值被赋予 1 分。相应地,患者被归类为 MFC(评分=0,62.0%)、MFC(评分=1,29.5%)和 MFC(评分=2,8.5%)。与 MFC(55 个月)和 MFC(19 个月)相比,MFC 具有显著更长的中位 OS(未达到)。我们将 MFC 整合到既定模型中,以替代形态学 PB 原始细胞计数。根据 MFC 增强评分对患者进行重新分类,并比较一致性(C-)指数。关于 IPSS,标准和 MFC 增强模型的 C-指数分别为 0.67 和 0.74(Z 分数-3.82;p=0.0001)。在 PMF 患者中,增强的 MIPSS70+模型的 MFC 获得了 0.78 的 C-指数,优于其标准对应物(C-指数 0.73;Z 分数-2.88,p=0.004)。我们的数据表明,从用于 CD34+细胞测定的标准测定中容易获得的 MFC 衍生参数的纳入可能有助于细化骨髓纤维化的当前预后分层模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bee7/9682857/0873e8241b00/AJH-97-846-g002.jpg

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