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Two Cases of Anti-D Alloimmunization in D-Negative Thai Patients as a Result of the Asian-Type DEL on Transfused Red Cells 两例泰国d阴性患者因输注红细胞出现亚洲型DEL而产生抗d异体免疫

4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-09-14 DOI: 10.1159/000533625

Kanyapon Suksard, Komon Luangtrakool, Thongbai Rungroung, Sutthisak Chamsai, Pradermchai Saetam, Kulvara Kittisares, Parichart Permpikul, Janejira Kittivorapart

Introduction: DEL is known to be one of the weakest D variants, which can be detected by the adsorption-elution technique or by molecular study. Currently, in Thailand, we do not routinely test for DEL variants serologically or genetically among serologic RhD-negative blood donors. Case Presentation: We reported 2 cases of alloimmunization after transfused with Rh DEL, RHD*DEL1 allele, in the Thai population. The first case was a 73-year-old male with anemia who presented with post-cardiac arrest and septic shock. The patient was group B, RhD-negative, and was transfused with RhD-negative red blood cells (RBCs). Antibody screening and identification found that the patient developed anti-D and anti-Mi^a during the admission course. The second case was a 38-year-old woman with pseudomyxoma peritonei who developed anti-D after receiving four units of RhD-negative RBCs during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Both patients did not receive anti-D immunoglobulin and had no previous history of anti-D detection. We retrospectively investigated and found two units of RHD*DEL1 among the RBCs transfused to these patients. Discussion: Previous reports of several cases of anti-D alloimmunization in RhD-negative recipients transfused by RHD*DEL1, an Asian-type DEL, are limited only to East Asia. We first identified 2 patients with anti-D alloimmunization after receiving the RHD*DEL1 RBCs in the Thai population. This raises concern about Rh DEL screening among D-negative Thai blood donors and whether to remove DEL units from the D-negative inventory to improve patient safety.

& lt; b> & lt; i>简介:& lt; / i> & lt; / b>DEL是已知的最弱的D变异之一，可以通过吸附-洗脱技术或分子研究来检测。目前，在泰国，我们没有在血清学rh阴性献血者中常规检测DEL变异的血清学或遗传学。& lt; b> & lt; i>案例表示:& lt; / i> & lt; / b>我们报告了2例输血Rh DEL后异体免疫，RHD*DEL1等位基因，在泰国人群中。第一个病例是73岁男性贫血，表现为心脏骤停和感染性休克。患者为B组，rh阴性，输注rh阴性红细胞(rbc)。抗体筛选鉴定发现患者出现抗- d和抗- mi< sup<在录取过程中。第二个病例是一名38岁的女性，她患有腹膜假性黏液瘤，在细胞减少手术和腹腔内高温化疗中接受4个单位的rhd阴性红细胞后出现抗d。两例患者均未接受抗d免疫球蛋白治疗，既往无抗d检测史。我们回顾性调查并发现了两个单位的RHD*DEL1在输血给这些病人的红细胞中& lt; b> & lt; i>讨论:& lt; / i> & lt; / b>先前关于RHD阴性受体输注RHD*DEL1(一种亚洲型DEL)发生抗d异体免疫的几例报道仅局限于东亚。我们首先发现2例患者在接受RHD*DEL1泰国人口中的红细胞。这引起了人们对在d阴性泰国献血者中进行Rh DEL筛查以及是否从d阴性库存中删除DEL单位以改善患者安全的关注。

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引用次数: 0

Moleculargenetic and in Addition Partly Discrepant Infection Serological Malaria Testing in Two Blood Donors 两名献血者的分子遗传学和部分差异感染血清学疟疾检测

4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-09-11 DOI: 10.1159/000530141

Lutz Pichl, Katja Konietzko, Ludwig Hartmann, Bogdan Puscasu, Carlos Jiménez Klingberg

Introduction: According to the guidelines (GL) valid in Germany, persons born or raised in a malaria-endemic area or had continuously stayed in a malaria-endemic area for more than 6 months may only be admitted donating blood if, among other things, validated and quality-assured laboratory diagnostics show that there is no evidence of infectivity. In a statement of the Working Group "Blood" of the Federal Ministry of Health (WGB), a reduction of the deferral period from 4 to 3 years and an antibody test after the deferral period are recommended. Methods: In accordance with the GL, nucleic acid testing (NAT) by means of PCR is carried out at our institution after a retention period of 4 years. In addition to the validated molecular biological testing, an infection serological examination was performed. Case Presentation: In the present cases, Plasmodia genome was detected in the respective single PCR in two blood donors originating from malaria-endemic areas after the expiry of the deferral period. However, one donor tested negative for antibodies against Plasmodia. Discussion/Conclusion: This observation is discussed in the context of a recommendation of the WGB. The question is addressed whether PCR testing is dispensable or whether a combination of infection serological testing and NAT should be favored.

& lt; b> & lt; i>简介:& lt; / i> & lt; / b>根据在德国有效的指南(GL)，在疟疾流行地区出生或长大的人，或连续在疟疾流行地区停留超过6个月的人，只有在经过验证和质量保证的实验室诊断表明没有传染性证据的情况下，才能被允许献血。在联邦卫生部"血液"工作组的一份声明中，建议将推迟期从4年缩短至3年，并在推迟期之后进行抗体检测。& lt; b> & lt; i>方法:& lt; / i> & lt; / b>根据GL，我机构在保存期4年后进行PCR核酸检测(NAT)。除了有效的分子生物学检测外，还进行了感染血清学检查。& lt; b> & lt; i>案例表示:& lt; / i> & lt; / b>在目前的情况下，疟原虫在延迟期结束后，在来自疟疾流行地区的两名献血者各自的单次PCR中检测到基因组。然而，一名供体的疟原虫抗体检测呈阴性。& lt; b> & lt; i>讨论/结论:& lt; / i> & lt; / b>这一观点是在工作组的一项建议的背景下讨论的。问题是是否PCR检测是可有可无的，或者是否应该支持感染血清学检测和NAT的组合。

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引用次数: 0

Stem Cell Mobilization, Collection, and Processing. 干细胞动员、收集和处理。

IF 1.9 4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-09-05 eCollection Date: 2023-10-01 DOI: 10.1159/000533649

Katharina Kriegsmann, Patrick Wuchter

引用次数: 0

56. Jahrestagung der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie e. V. (DGTI), 20.–22. September 2023, Berlin, ABSTRACTS 56.德国输血医学和免疫血液学学会年会，20-22。2023年9月，柏林，摘要

IF 2.2 4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-09-01 DOI: 10.1159/000533306

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没有一个

引用次数: 1

Prelims 预备考试

IF 2.2 4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-09-01 DOI: 10.1159/000533229

引用次数: 0

Validation of a Parvovirus B19 NAT Assay for Screening of Umbilical Cord Blood for Allogenic Hematopoietic Stem Cell Donation 细小病毒B19 NAT检测筛选脐带血供同种异体造血干细胞捐献的验证

4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-08-30 DOI: 10.1159/000532073

Philipp Steininger, Klaus Korn, Holger Hackstein, Erwin F. Strasser

Introduction: Parvovirus B19 transmitted by umbilical cord blood (UCB) products may cause severe disease in allogenic hematopoietic stem cell transplant recipients. Thus, commercially available nucleic acid test (NAT) assays for highly sensitive detection of parvovirus B19 DNA validated for the specimen cord blood plasma (CBP) are required to avoid parvovirus B19 transmission by umbilical hematopoietic stem cell preparations. Methods: The multiplex cobas DPX NAT assay was validated for detection of parvovirus B19 DNA in CBP derived from citrate anticoagulated UCB units which have been processed by the Rubinstein method. In total, 363 retained CBP samples pretested negative for parvovirus B19 DNA were prepared for analyzing sensitivity, specificity, and interference of that NAT assay. The 3rd WHO International Standard for parvovirus B19 DNA was used for determining the 95% limit of detection (LOD95) by probit analysis. Results: The validation of the parvovirus B19 NAT assay for CBP demonstrated high sensitivity, specificity, intra- and inter-assay precision. Dilution series and replicate analyses showed a high linearity of the assay with a coefficient of determination above 0.99 and revealed a LOD95 of 17 International Units (IU)/mL (95% confidence interval, 14–44 IU/mL) for parvovirus B19 DNA in CBP samples. Conclusion: The validation of a commercially available parvovirus B19 NAT assay for the specimen CBP demonstrated a high assay performance fulfilling German guidelines and international regulations.

& lt; b> & lt; i>简介:& lt; / i> & lt; / b>通过脐带血(UCB)制品传播的细小病毒B19可能导致同种异体造血干细胞移植受者发生严重疾病。因此，为避免细小病毒B19通过脐带血血浆(CBP)传播，需要商用核酸检测(NAT)方法对细小病毒B19 DNA进行高灵敏度检测。& lt; b> & lt; i>方法:& lt; / i> & lt; / b>多重cobas DPX NAT检测方法可用于Rubinstein法处理的柠檬酸抗凝UCB单元CBP中细小病毒B19 DNA的检测。共制备363份保留的CBP样品，预检测细小病毒B19 DNA阴性，用于分析NAT检测的敏感性、特异性和干扰性。采用世界卫生组织细小病毒B19 DNA第三版国际标准，采用概率分析法测定95%检出限(LOD95)。& lt; b> & lt; i>结果:& lt; / i> & lt; / b>细小病毒B19 NAT检测CBP具有较高的灵敏度、特异性和检测内、间精度。稀释系列和重复分析显示，该检测方法线性度高，测定系数大于0.99，显示CBP样品中细小病毒B19 DNA的LOD95为17国际单位(IU)/mL(95%可信区间为14-44 IU/mL)。& lt; b> & lt; i>结论:& lt; / i> & lt; / b>市售的细小病毒B19 NAT检测对CBP标本的验证显示出高检测性能，符合德国指南和国际法规。

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引用次数: 0

Efficient Chimeric Antigen Receptor T-Cell Generation Starting with Leukoreduction System Chambers of Thrombocyte Apheresis Sets 高效嵌合抗原受体t细胞生成开始与白细胞诱导系统室的血小板分离装置

4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-08-30 DOI: 10.1159/000532130

Stefani Xhaxho, Linping Chen-Wichmann, Sophie Kreissig, Roland Windisch, Adrian Gottschlich, Sayantan Nandi, Sophie Schabernack, Irmgard Kohler, Christian Kellner, Sebastian Kobold, Andreas Humpe, Christian Wichmann

Introduction: Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology. Normally, the LRSC is discarded after apheresis is completed. Compared to peripheral blood, LRSC yields 10-fold mononuclear cell concentration. Methods: To explore if those retained leukocytes are attractive for research purposes, we isolated CD3+ T cells from the usually discarded LRSCs via density gradient centrifugation in order to manufacture CD19-targeted chimeric antigen receptor (CAR) T cells. Results: Immunophenotypic characterization revealed viable and normal CD4+ and CD8+ T-cell populations within LRSC, with low CD19+ B cell counts. Magnetic-activated cell sorting (MACS) purified CD3+ T cells were transduced with CD19 CAR-encoding lentiviral self-inactivating vectors using concentrated viral supernatants. Robust CD19 CAR cell surface expression on transduced T cells was confirmed by flow cytometry. CD19 CAR T cells were further enriched through anti-CAR MACS, yielding 80% CAR+ T-cell populations. In vitro CAR T cell expansion to clinically relevant numbers was achieved. To prove functionality, CAR T cells were co-incubated with the human CD19+ B cell precursor leukemia cell line Nalm6. Compared to unmodified T cells, CD19 CAR T cells effectively eradicated Nalm6 cells. Conclusion: Taken together, we can show that lymphocytes isolated from LRSCs of plateletpheresis sets can be efficiently used for the generation of functional CAR T cells for experimental purposes.

& lt; b> & lt; i>简介:& lt; / i> & lt; / b>人原代血细胞是研究生理和疾病的重要模型系统。然而，人类血液是一种有限的资源。在健康供体采血小板过程中，白细胞诱导系统腔室(LRSC)通过饱和、流态化、颗粒床过滤技术减少随后血小板浓缩物中的白细胞数量。正常情况下，在分离完成后，LRSC将被丢弃。与外周血相比，LRSC产生10倍的单核细胞浓度。& lt; b> & lt; i>方法:& lt; / i> & lt; / b>为了探索这些保留的白细胞是否对研究目的有吸引力，我们通过密度梯度离心从通常丢弃的LRSCs中分离出CD3+ T细胞，以制造cd19靶向嵌合抗原受体(CAR) T细胞。& lt; b> & lt; i>结果:& lt; / i> & lt; / b>免疫表型表征显示LRSC内存活和正常的CD4+和CD8+ t细胞群，CD19+ B细胞计数低。磁活化细胞分选(MACS)纯化的CD3+ T细胞用CD19 car编码慢病毒自灭活载体使用浓缩病毒上清转导。流式细胞术证实CD19 CAR细胞表面在转导的T细胞上表达稳健。通过抗CAR - MACS进一步富集CD19 CAR - T细胞，产生80%的CAR+ T细胞群。体外CAR - T细胞扩增达到临床相关数量。为了证明功能，CAR - T细胞与人类CD19+ B细胞前体白血病细胞系Nalm6共孵育。与未经修饰的T细胞相比，CD19 CAR - T细胞有效地根除了Nalm6细胞。& lt; b> & lt; i>结论:& lt; / i> & lt; / b>综上所述，我们可以证明，从血小板采集集的LRSCs中分离的淋巴细胞可以有效地用于生成功能性CAR - T细胞，用于实验目的。

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引用次数: 0

Mobilization Strategies in Myeloma Patients Intended for Autologous Hematopoietic Cell Transplantation. 骨髓瘤患者自体造血细胞移植的动员策略。

IF 2.2 4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-08-24 eCollection Date: 2023-10-01 DOI: 10.1159/000531940

Esa Jantunen, Anu Partanen, Antti Turunen, Ville Varmavuo, Raija Silvennoinen

Background: Multiple myeloma is currently the leading indication for autologous hematopoietic cell transplantation (AHCT). A prerequisite for AHCT is mobilization and collection of adequate blood graft to support high-dose therapy. Current mobilization strategies include granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy most commonly cyclophosphamide (CY). More recently, plerixafor has become into agenda especially in patients who mobilize poorly. In the selection of a mobilization method, several factors should be considered.

Summary: Preplanned collection target is important as G-CSF plus plerixafor is more effective in the mobilization of CD34⁺ cells than G-CSF alone. On the other hand, CY plus G-CSF is superior to G-CSF only mobilization. Previous therapy and age of the patients are important considerations as G-CSF alone may not be effective enough in patients with risk factors for poor mobilization. These factors include extensive lenalidomide exposure, irradiation to bone marrow-bearing sites, higher age, or a previous mobilization failure. Also, local preferences and experiences as well as the number of apheresis needed are important issues as well as cost-effectiveness considerations. Mobilization method used may have implication for cellular composition of collected grafts, which might have an impact on posttransplant events such as hematologic and immune recovery in addition to also potential long-term outcomes.

Key message: Currently, G-CSF alone and preemptive plerixafor if needed might be considered as a standard mobilization strategy in MM patients intended for AHCT.

背景：多发性骨髓瘤是目前自体造血细胞移植（AHCT）的主要适应症。AHCT的先决条件是动员和收集足够的移植物来支持高剂量治疗。目前的动员策略包括单独使用粒细胞集落刺激因子（G-CSF）或与化疗联合使用，最常见的是环磷酰胺（CY）。最近，普乐沙福已经成为一项议程，尤其是在那些行动不便的患者中。在选择动员方法时，应考虑几个因素。总结：预先计划的收集靶点很重要，因为G-CSF加普利沙福在动员CD34+细胞方面比单独的G-CSF更有效。另一方面，CY加G-CSF动员优于仅G-CSF动员。先前的治疗和患者的年龄是重要的考虑因素，因为单独的G-CSF对有动员不良危险因素的患者可能不够有效。这些因素包括广泛的来那度胺暴露、骨髓承载部位的照射、较高的年龄或先前的动员失败。此外，当地的偏好和经验以及需要单采的数量也是重要的问题，也是成本效益方面的考虑因素。所使用的动员方法可能对收集的移植物的细胞组成有影响，这可能对移植后事件产生影响，如血液学和免疫恢复，以及潜在的长期结果。关键信息：目前，如果需要，单独使用G-CSF和先发制人的普利沙福可能被视为用于AHCT的MM患者的标准动员策略。

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引用次数: 1

CD34⁺ Cell Mobilization, Autograft Cellular Composition and Outcome in Mantle Cell Lymphoma Patients. CD34+细胞动员、自体移植物细胞组成和套细胞淋巴瘤患者的预后。

IF 2.2 4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-08-23 eCollection Date: 2023-10-01 DOI: 10.1159/000531799

Antti Samuli Turunen, Outi Kuittinen, Hanne Kuitunen, Kaija Vasala, Karri Penttilä, Minna Harmanen, Leena Keskinen, Pentti Mäntymaa, Jukka Pelkonen, Ville Varmavuo, Esa Jantunen, Anu Partanen

Backgound: Autologous stem cell transplantation (ASCT) is a standard treatment in transplant-eligible mantle cell lymphoma (MCL) patients after first-line chemoimmunotherapy.

Study design and methods: This prospective multicenter study evaluated the impact of CD34⁺ cell mobilization and graft cellular composition analyzed by flow cytometry on hematologic recovery and outcome in 42 MCL patients.

Results: During CD34⁺ cell mobilization, a higher blood CD34⁺ cell count (>30 × 10⁶/L) was associated with improved overall survival (median not reached [NR] vs. 57 months, p = 0.04). The use of plerixafor did not impact outcome. Higher number of viable cryopreserved graft CD34⁺ cells (>3.0 × 10⁶/kg) was associated with faster platelet (median 11 vs. 15 days, p = 0.03) and neutrophil (median 9 vs. 10 days, p = 0.02) recovery posttransplant. Very low graft CD3⁺CD8⁺ cell count (≤10 × 10⁶/kg) correlated with worse progression-free survival (PFS) (HR 4.136, 95% CI 1.547-11.059, p = 0.005). On the other hand, higher absolute lymphocyte count >2.5 × 10⁹/L at 30 days after ASCT (ALC-30) was linked with better PFS (median NR vs. 99 months, p = 0.045) and overall survival (median NR in either group, p = 0.05).

Conclusions: Better mobilization capacity and higher graft CD3⁺CD8⁺ cell count had a positive prognostic impact in this study, in addition to earlier lymphocyte recovery (ALC-30>2.5 × 10⁶/L). These results need to be validated in another study with a larger patient cohort.

背景：自体干细胞移植（ASCT）是一线化学免疫治疗后符合移植条件的套细胞淋巴瘤（MCL）患者的标准治疗方法。研究设计和方法：这项前瞻性多中心研究评估了流式细胞术分析的CD34+细胞动员和移植物细胞组成对42名MCL患者血液学恢复和预后的影响。结果：在CD34+细胞动员过程中，较高的血液CD34+细胞计数（>30×106/L）与总生存率的提高有关（中位未达到[NR]，而57个月，p=0.04）。使用普利沙福不会影响结果。更高数量的活的冷冻保存移植物CD34+细胞（>3.0×106/kg）与移植后更快的血小板（中位数11天与15天，p=0.03）和中性粒细胞（中位数9天与10天，p=0.02）恢复有关。极低的移植物CD3+CD8+细胞计数（≤10×106/kg）与较差的无进展生存期（PFS）相关（HR 4.136，95%CI 1.547-11.059，p=0.005），ASCT（ALC-30）后30天，较高的绝对淋巴细胞计数>2.5×109/L与较好的PFS（中位NR vs.99个月，p=0.045）和总生存率（两组中位NR，p=0.05）有关。这些结果需要在另一项具有更大患者队列的研究中得到验证。

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引用次数: 1

Quartic CAR-T Cell Bridging to Twice Allo-HSCT Therapy in a Patient with Acute Lymphoblastic Leukemia 急性淋巴细胞白血病患者四次CAR-T细胞桥接两次同种异体造血干细胞移植治疗

4区医学 Q3 HEMATOLOGY

Transfusion Medicine and Hemotherapy

Pub Date : 2023-08-22 DOI: 10.1159/000531681

Qing Zhang, Yi Dong, Zhimin Zhai, Qianshan Tao

Introduction: Chimeric antigen receptor T (CAR-T) cell therapy is an effective bridging treatment for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in relapsed or refractory acute lymphoblastic leukemia (ALL). However, repetitive CAR-T cell therapy and allo-HSCT can only be performed in a few patients because of technical difficulties and patients’ physical, economic, and social conditions. Case Presentation: A 23-year-old female patient with second relapsed B-cell ALL (B-ALL) underwent human-murine chimeric CD19 CAR-T cell therapy twice, human-murine chimeric CD22 CAR-T cell therapy once, and humanized CD19 CAR-T cell therapy once. Moreover, she was sequentially bridged to her mother donor allo-HSCT once and cousin donor allo-HSCT once. Conclusion: Repetitive CAR-T cell therapy bridging to repetitive allo-HSCT is still a safe and active therapeutic strategy for patients with relapsed or refractory ALL.

& lt; b> & lt; i>简介:& lt; / i> & lt; / b>嵌合抗原受体T (CAR-T)细胞疗法是治疗复发或难治性急性淋巴细胞白血病(ALL)的同种异体造血干细胞移植(alloo - hsct)的有效桥接疗法。然而，由于技术上的困难以及患者的身体、经济和社会条件，重复CAR-T细胞治疗和同种异体造血干细胞移植只能在少数患者中进行。& lt; b> & lt; i>案例表示:& lt; / i> & lt; / b>一位23岁的女性b细胞ALL (B-ALL)二次复发患者接受了2次人鼠嵌合CD19 CAR-T细胞治疗，1次人鼠嵌合CD22 CAR-T细胞治疗，1次人源化CD19 CAR-T细胞治疗。此外，她先后接受了一次母亲的同种异体造血干细胞移植和一次表亲的同种异体造血干细胞移植。& lt; b> & lt; i>结论:& lt; / i> & lt; / b>对于复发或难治性ALL患者，重复CAR-T细胞治疗与重复同种异体造血干细胞移植的桥接仍然是一种安全而积极的治疗策略。

引用次数: 0

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