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A comparative analysis of the clinical and genetic profiles of blast phase BCR::ABL1-negative myeloproliferative neoplasm and acute myeloid leukemia, myelodysplasia-related 胚泡期BCR::ABL1阴性骨髓增生性肿瘤和骨髓增生异常相关急性髓性白血病的临床和遗传特征对比分析。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-26 DOI: 10.1111/ijlh.14280
Dong Chen, Julia Geyer, Adam Bagg, Robert Hasserjian, Olga K. Weinberg

Introduction

The classic Philadelphia chromosome–negative myeloproliferative neoplasms (Ph (-) MPNs), have variable potential for progression to the blast phase (MPN-BP) of the disease. Except initiated by distinct driver mutations, MPN-BP frequently carry similar genetic abnormalities defining acute myeloid leukemia myelodysplasia-related (AML-MR). Because of dissimilar initial pathogenesis, MPN-BP and AML-MR are retained under different disease categories. To determine if separately classifying these entities is justified, we compare MPN-BP with AML-MR patients based on mutational landscape and clinical parameters.

Methods

104 MPN-BP patients and 145 AML-MR patients were identified with available clinical, cytogenetic, and genetic data.

Results

AML-MR patients presented with a higher blast count (median, 51% vs. 30%) while MPN-BP patients had higher WBC counts, platelet counts and bone marrow cellularity (all p<0.0001). Patients with MPN-BP showed similar genetic mutations with similar mutation pattern (functional domain, hotspot and locus involved by the mutations) but a different mutation rate from AML-MR, with more frequent JAK2, CALR, MPL, ASXL1, IDH2, SETBP1 and SRSF2 mutations and less frequent TP53 and DNMT3A mutations. The overall survival (OS) of MPN-BP (OS post-BP-progression) is comparable to that of AML-MR (median OS, 9.5 months vs. 13.1 months, p=0.20). In addition, the subgroups of MPN-BP show similar OS as AML-MR. When harboring certain mutation such as TP53, ASXL1, DNMT3A, TET2, RUNX1, IDH1, IDH2, EZH2, U2AF1, BCOR and SRSF2, MPN-BP and AML-MR patients carrying the same somatic mutation show no difference in OS.

Conclusion

MPN-BP and AML-MR harbor similar somatic mutations and clinical outcomes, suggesting a unified clinical disease entity.

导言:典型的费城染色体阴性骨髓增殖性肿瘤(Ph (-) MPNs)有不同的潜能发展到疾病的爆发期(MPN-BP)。除了由不同的驱动基因突变引发外,MPN-BP 经常携带与急性髓性白血病骨髓增生异常相关(AML-MR)类似的基因异常。由于初始发病机制不同,MPN-BP 和 AML-MR 被归入不同的疾病类别。为了确定将这两种疾病分开分类是否合理,我们根据突变情况和临床参数对 MPN-BP 和 AML-MR 患者进行了比较。 结果AML-MR 患者的胚泡计数较高(中位数为 51% 对 30%),而 MPN-BP 患者的白细胞计数、血小板计数和骨髓细胞数都较高(均 p<0.0001)。MPN-BP 患者的基因突变相似,突变模式(功能域、热点和突变涉及的位点)相似,但突变率与 AML-MR 不同,JAK2、CALR、MPL、ASXL1、IDH2、SETBP1 和 SRSF2 突变较多,而 TP53 和 DNMT3A 突变较少。MPN-BP的总生存期(OS)(BP进展后的OS)与AML-MR相当(中位OS,9.5个月对13.1个月,P=0.20)。此外,MPN-BP 亚组的 OS 与 AML-MR 相似。当MPN-BP和AML-MR携带某些突变时,如TP53、ASXL1、DNMT3A、TET2、RUNX1、IDH1、IDH2、EZH2、U2AF1、BCOR和SRSF2,携带相同体细胞突变的MPN-BP和AML-MR患者的OS没有差异。
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引用次数: 0
Circulating lobular breast carcinoma cells 循环小叶乳腺癌细胞
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-24 DOI: 10.1111/ijlh.14295
Brent Tan, Jean Oak
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引用次数: 0
Applicability of mono dysplasia score on the new Sysmex XR analyzer range to predict diagnosis of chronic myelomonocytic leukaemia 新型 Sysmex XR 分析仪系列的单核细胞发育不良评分预测慢性粒细胞白血病诊断的适用性。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-23 DOI: 10.1111/ijlh.14296
Edouard Cornet, Sandrine Girard, Romain Blottiere, Agnès Leonard, Lucile Deloriere, Céline Bossard, Pauline Kerneves, Yohann Repesse
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引用次数: 0
Immune reconstitution in children after haploidentical haematopoietic stem cell transplantation 单倍体造血干细胞移植后儿童的免疫重建。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-22 DOI: 10.1111/ijlh.14290
Saranthorn Apasuthirat, Nopporn Apiwattanakul, Usanarat Anurathapan, Nintita Sripaiboonkij Thokanit, Karan Paisooksantivatana, Ekawat Pasomsub, Suradej Hongeng, Samart Pakakasama

Introduction

Immune reconstitution (IR) kinetics of paediatric patients underwent haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCy) have not been extensively studied. We compared IR patterns of children receiving HSCT from haploidentical (n = 92) and HLA-matched donors (n = 36), and analysed risk factors for viral infection in these patients.

Methods

We prospectively measured lymphocyte subset numbers before HSCT and at 1, 3, 6 and 12 months after HSCT. Blood cytomegalovirus (CMV), Epstein–Barr virus, adenovirus, BK virus (BKV) and urine adenovirus and BKV viral loads were measured at designated time points.

Results

The median numbers of total T and T helper cells at 1 month were significantly lower in the haploidentical group compared with the HLA-matched group. Haploidentical HSCT recipients had significantly lower median numbers of several T cell subsets and B cells for 1 year after HSCT. The median NK cell count of the haploidentical group was lower at 1 month. BKV haemorrhagic cystitis, blood CMV and urine adenovirus reactivation were more frequently found in the haploidentical group. Post-haploidentical HSCT patients receiving anti-T lymphocyte globulin (ATG) had significantly lower median numbers of total T cells (at 1 month) and T helper cells (at 6 and 12 months) and higher rate of blood BKV reactivation compared with those without ATG.

Conclusion

Paediatric patients who undergo haploidentical HSCT with PTCy are likely to have delayed IR and an increased risk of viral reactivation/infection compared with HLA-matched HSCT. The addition of ATG to PTCy delayed T cell recovery and increased risk of BKV reactivation.

简介对接受单倍体造血干细胞移植(HSCT)并在移植后使用环磷酰胺(PTCy)的儿童患者的免疫重建(IR)动力学尚未进行广泛研究。我们比较了接受单倍体(92人)和HLA匹配供者(36人)造血干细胞移植的儿童的IR模式,并分析了这些患者病毒感染的风险因素。在指定的时间点测量血液中巨细胞病毒(CMV)、爱泼斯坦-巴氏病毒(Epstein-Barr virus)、腺病毒、BK病毒(BKV)以及尿液中腺病毒和BKV病毒载量。结果:与HLA配型组相比,单倍体组在1个月时总T细胞和T辅助细胞的中位数明显较低。造血干细胞移植后一年,单倍体造血干细胞移植受者的多个T细胞亚群和B细胞的中位数明显降低。单倍体组的 NK 细胞数量中位数在 1 个月时较低。在单倍体组中,BKV出血性膀胱炎、血液中CMV和尿液中腺病毒再活化的发生率更高。接受抗 T 淋巴细胞球蛋白(ATG)的单倍体造血干细胞移植后患者与未接受 ATG 的患者相比,总 T 细胞(1 个月时)和 T 辅助细胞(6 个月和 12 个月时)的中位数明显较低,血液中 BKV 再激活率较高。在 PTCy 中加入 ATG 会延迟 T 细胞的恢复,增加 BKV 再激活的风险。
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引用次数: 0
Oligomonocytic chronic myelomonocytic leukemia is eligible to MDS-score and not Mono-dysplasia score 少单核细胞型慢性粒细胞白血病符合 MDS 评分标准,但不符合单核细胞增生异常评分标准。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-21 DOI: 10.1111/ijlh.14294
Benjamin Podvin, Marion Magierowicz, Valérie Soenen, Florent Dumezy, Nicolas Duployez, Agnès Charpentier
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引用次数: 0
Acidosis can temporarily and markedly prolong APTT 酸中毒可暂时明显延长 APTT。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-21 DOI: 10.1111/ijlh.14293
Anne M. Sermon-Cadd, Lee J. Beckett, Steve Kitchen
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引用次数: 0
Performance of direct oral anticoagulant (DOAC) testing by hemostasis laboratories: The Australasian/Asia-Pacific experience 止血实验室进行直接口服抗凝剂(DOAC)检测的情况:澳大拉西亚/亚太地区的经验。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-21 DOI: 10.1111/ijlh.14288
Emmanuel J. Favaloro, Sandya Arunachalam, Elysse Dean

Introduction

Direct oral anticoagulants (DOACs) reflect anticoagulation agents given to treat or prevent thrombosis, having largely replaced vitamin K antagonists (VKAs) such as warfarin. DOACs are given in fixed daily doses and generally do not need monitoring. However, there may be a variety of reasons that justify measurement of plasma DOAC levels in individual patients.

Methods

We report updated findings for DOAC testing in our geographic region, using recent data from the RCPAQAP, an international external quality assessment (EQA) program, currently with some 40–60 participants in each of the different DOAC (rivaroxaban, apixaban, dabigatran) modules, to assess laboratory performance in this area. Data has been assessed for the past 5 years (2019–2023 inclusive), with 20 samples each per DOAC.

Results

Data shows a limited repertoire of assays in use, and mostly consistency in reported numerical values when assessing proficiency samples. Available assays mostly comprised reagents from four manufacturing suppliers. There was good consistency across what participants identified as ‘DOAC detected’, but some variability when participants attempted to grade DOAC levels as low vs moderate vs high. Inter-laboratory/method coefficient of variation (CVs) were generally <15% for each DOAC, when present at >100 ng/mL.

Conclusion

We hope our findings, reflecting on mostly consistent reporting of DOAC levels and interpretation provides reassurance for clinicians requesting these measurements, and helps support their implementation in regions where there is a paucity of test availability.

简介 直接口服抗凝剂(DOACs)是用于治疗或预防血栓形成的抗凝剂,已在很大程度上取代了华法林等维生素 K 拮抗剂(VKAs)。DOACs 每日剂量固定,一般无需监测。我们利用国际外部质量评估 (EQA) 计划 RCPAQAP 的最新数据报告了本地区 DOAC 检测的最新结果,目前每个不同的 DOAC(利伐沙班、阿哌沙班、达比加群)模块都有约 40-60 名参与者,以评估该领域的实验室绩效。对过去 5 年(2019-2023 年,含 2019-2023 年)的数据进行了评估,每种 DOAC 各评估 20 份样本。结果 数据显示,使用的检测方法种类有限,在评估能力样本时,报告的数值大多具有一致性。可用的检测方法主要包括来自四家生产供应商的试剂。参与者认定的 "检出 DOAC "具有很好的一致性,但当参与者试图将 DOAC 水平分为低、中、高时,则存在一些差异。结论我们希望我们的研究结果,即对 DOAC 水平和解释的报告基本一致,能为要求进行这些测量的临床医生提供保证,并有助于支持在缺乏检测方法的地区实施这些方法。
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引用次数: 0
New method to differentiate between lupus anticoagulants, progressive coagulation inhibitors and coagulation factor deficiencies in the mixing tests 在混合试验中区分狼疮抗凝剂、进行性凝血抑制剂和凝血因子缺乏症的新方法。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-21 DOI: 10.1111/ijlh.14289
Daiki Shimomura, Osamu Kumano, Kaori Ueda, Keisuke Kitano, Nobuo Arai, Masashi Shimada, Mikio Kamioka

Introduction

Mixing tests in activated partial thromboplastin time (APTT) are used for the differentiation between lupus anticoagulants (LA), coagulation inhibitors, and factor deficient samples with APTT prolongation. However, the indexes for the differentiation have not been established. The present study aimed to develop new mixing test indexes for the differentiation.

Methods

Twenty-six LA-positive, 8 progressive coagulation factor VIII inhibitor, and 35 coagulation deficient samples were employed. APTT were measured for normal plasma, patient plasma, and mixing plasma prepared at a ratio of 1:1 proportion in both without incubation and 2 h-incubation. New two parameters named as ALD50 and mixture plasma—patient plasma after Warming change rate Subtraction (WaS) calculated from the clotting times of normal, 1:1 mixing and patient samples with/without 2 h-incubation were established. In the samples with WaS result of <10.2%, ALD50 of ≥87.8%, and < 87.8% were defined as LA and coagulation factor deficiency, respectively, and WaS of ≥10.2% defined progressive coagulation factor inhibitors.

Results

Sensitivity and specificity to LA were 80.8% and 93.0% for ALD50, and sensitivity and specificity to progressive coagulation factor inhibitor were 100.0% and 100.0% for WaS, respectively. The agreement between sample classification and WaS-ALD50 was 88.4% (61/69).

Conclusions

ALD50 and WaS showed acceptable sensitivity and specificity to LA and progressive coagulation factor inhibitor, respectively. These indexes would be useful for the differentiation between LA, factor deficiency, and progressive coagulation factor inhibitor in the mixing tests.

简介:活化部分凝血活酶时间(APTT)混合试验用于区分狼疮抗凝物(LA)、凝血抑制剂和 APTT 延长的因子缺乏样本。然而,用于区分的指标尚未确定。本研究旨在开发新的混合试验区分指标。对正常血浆、患者血浆和按 1:1 比例制备的混合血浆在不孵育和孵育 2 小时的情况下进行 APTT 测量。根据正常血浆、1:1 混合血浆和患者血浆在孵育 2 小时或不孵育 2 小时后的凝血时间计算出新的两个参数,即 ALD50 和升温变化率减法(WaS)后的混合血浆-患者血浆。结果ALD50对LA的敏感性和特异性分别为80.8%和93.0%,WaS对进行性凝血因子抑制的敏感性和特异性分别为100.0%和100.0%。样本分类与WaS-ALD50的一致性为88.4%(61/69)。这些指标有助于在混合试验中区分 LA、因子缺乏和进行性凝血因子抑制。
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引用次数: 0
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Obinutuzumab interference with immunoelectrophoresis in a case of follicular lymphoma 卵泡淋巴瘤病例中的奥比妥珠单抗对免疫电泳的干扰
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-04-16 DOI: 10.1111/ijlh.14284
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引用次数: 0
期刊
International Journal of Laboratory Hematology
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