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Anti-CD38 monoclonal antibody impairs CD34+ mobilization and affects clonogenic potential in multiple myeloma patients. 抗 CD38 单克隆抗体会损害多发性骨髓瘤患者的 CD34+ 动员能力并影响其克隆生成潜能。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-07-01 DOI: 10.2450/BloodTransfus.667
Arianna Zappaterra, Ivan Civettini, Anna Maria Cafro, Laura Pezzetti, Silvia Pierini, Michela Anghilieri, Laura Bellio, Paola Bertazzoni, Giovanni Grillo, Periana Minga, Maria L Pioltelli, Emanuele Ravano, Marianna Sassone, Clara V Viganò, Elisabetta B Volpato, Carlo Gambacorti-Passerini, Silvano Rossini, Roberto Cairoli, Roberto Crocchiolo

Background: Induction with daratumumab-based regimens followed by autologous stem cell transplantation is the current standard for newly diagnosed multiple myeloma (NDMM) patients eligible for intensive chemotherapy. However, concerns emerged regarding potential negative effects following daratumumab-based treatment on CD34+ mobilization. We here compared CD34+ mobilization and clonogenic potential between daratumumab and non-daratumumab based therapy without upfront plerixafor administration among patients affected by NDMM.

Materials and methods: Clinical, mobilization and clonogenic data from 41 consecutively enrolled NDMM patients were analyzed. Patients underwent collection of autologous CD34+ by apheresis at the ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, from January 2021 to March 2023. Clonogenicity analysis was performed on BFU-E and CFU-GM.

Results: Seventy-five percent of daratumumab-treated patients underwent >1 apheresis, compared to 24% of non-daratumumab patients (p=0.0017). Daratumumab-treated patients had significantly lower CD34+ count (mean 38 vs 79/μL, respectively; p=0.0011), with a median CD34+ harvest of 3.98×106/kg (range 1.68-9.18) vs 6.87×106/kg (range 1.63-16.85) in non-daratumumab-treated (p=0.0006). In multivariate analysis the likelihood of undergoing >1 apheresis was significantly higher in older patients (OR 1.2, 95% CI 1-1.4, Z=2.10, p=0.03) and daratumumab-treated patients (OR 15, 95% CI 2.8-129, p=0.004). Moreover, daratumumab-based induction therapy demonstrated an independent negative association with BFU-E colony formation (p=0.0148), even when accounting for patient age and CD34+ levels.

Discussion: Our findings underscore the impact of daratumumab-based treatment on CD34+ mobilization in a real-life, upfront plerixafor-free population of NDMM patients. Higher probability of requiring multiple apheresis occurred among daratumumab-treated patients. Interestingly, the observation that daratumumab might negatively impact BFU-E colony formation, independent of CD34+ cell count, offers novel biological perspectives. Appropriate strategies should be adopted by the Apheresis teams to mitigate these potential negative effects.

背景:对于符合强化化疗条件的新诊断多发性骨髓瘤(NDMM)患者,目前的标准是先用达拉单抗诱导,然后进行自体干细胞移植。然而,人们担心达拉单抗治疗后对CD34+动员可能产生负面影响。在此,我们比较了达拉单抗和非达拉单抗疗法对NDMM患者的CD34+动员和克隆生成潜能的影响:分析了41例连续入组的NDMM患者的临床、动员和克隆生成数据。患者于2021年1月至2023年3月在意大利米兰的ASST Grande Ospedale Metropolitano Niguarda医院接受了自体CD34+采集。对BFU-E和CFU-GM进行了克隆生成性分析:75%的达拉土单抗治疗患者接受了1次以上的血液净化治疗,而非达拉土单抗治疗患者的这一比例为24%(P=0.0017)。达拉土单抗治疗患者的CD34+计数明显较低(平均值分别为38 vs 79/μL;p=0.0011),CD34+收获量中位数为3.98×106/kg(范围1.68-9.18),而非达拉土单抗治疗患者为6.87×106/kg(范围1.63-16.85)(p=0.0006)。在多变量分析中,年龄较大的患者(OR 1.2,95% CI 1-1.4,Z=2.10,p=0.03)和达拉曲单抗治疗的患者(OR 15,95% CI 2.8-129,p=0.004)接受>1次血液净化的可能性明显更高。此外,即使考虑到患者年龄和CD34+水平,基于达拉单抗的诱导治疗与BFU-E集落形成呈独立负相关(p=0.0148):讨论:我们的研究结果强调了达拉单抗诱导治疗对NDMM患者CD34+动员的影响。接受达拉土单抗治疗的患者需要进行多次血液净化的概率更高。有趣的是,达拉土单抗可能会对BFU-E集落的形成产生负面影响,而与CD34+细胞数量无关,这一观察结果提供了新的生物学视角。血液净化团队应采取适当的策略来减轻这些潜在的负面影响。
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引用次数: 0
Insights and innovations in Blood Transfusion. 输血方面的见解和创新。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-07-01 DOI: 10.2450/BloodTransfus.845
Serelina Coluzzi, Luca Mascaretti
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引用次数: 0
Insights and innovations in Blood Transfusion. 输血方面的见解和创新。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-07-01 DOI: 10.2450/BloodTransfus.845
Serelina Coluzzi, Luca Mascaretti
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引用次数: 0
The role of erythropoietin to prevent red blood cell transfusion in a 2018-2020 two-center cohort of preterm infants. 2018-2020年双中心早产儿队列中促红细胞生成素在预防红细胞输注中的作用。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-07-01 DOI: 10.2450/BloodTransfus.641
Noémie Bailly, Roselyne Brat, Geraldine Favrais

Background: Treatment with recombinant human erythropoietin (rHu-EPO) modestly prevented packed red blood cell transfusions (pRBCTs) in preterm infants in studies performed several years ago. In France, some neonatal units stopped using rHu-EPO, while others continued. The aim of this study was to explore the role of rHu-EPO in the prevention of pRBCTs in a recent cohort of preterm infants.

Materials and methods: Preterm infants who met rHu-EPO indications and were hospitalised between 2018 and 2020 in two neonatal units -one that did not use rHu-EPO and another that did- were eligible. Data about the neonatal history, rHu-EPO and iron treatments and pRBCT indications and volumes were collected. Infants exposed and not exposed to rHu-EPO were compared in univariate and multivariate analyses using backward logistic regression and Cox proportional hazards regression.

Results: A total of 257 patients exposed to rHu-EPO and 285 patients who were not exposed were included. Three profiles emerged. In the infants with a gestational age <28 weeks, the cumulative pRBCT volume/kg was similar regardless of rHu-EPO exposure (mean difference -2.8 mL, 95% confidence interval -16.1, 10.5, p=0.68). In the infants born between 28 and 30 weeks, a late pRBCT was prevented in the rHu-EPO group (single pRBCT: no rHu-EPO 22.1% vs rHu-EPO 8%, p=0.003). However, rHu-EPO was not independently associated with avoidance of this pRBCT. Finally, the need for pRBCT was low in the infants born after 30 weeks of gestation, making rHu-EPO treatment futile. In contrast, early iron supplementation was revealed to be critical in preventing pRBCT.

Discussion: No benefit of rHu-EPO in preventing pRBCT was observed in our cohort. The place of rHu-EPO in future requires careful consideration of the population concerned, adjustment of the therapeutic schedule and evolution of the indications for pRBCT.

背景:在几年前进行的研究中,使用重组人促红细胞生成素(rHu-EPO)治疗可适度预防早产儿的包装红细胞输血(pRBCT)。在法国,一些新生儿科室停止使用 rHu-EPO,而另一些则继续使用。本研究旨在探讨 rHu-EPO 在最近一批早产儿中预防 pRBCT 的作用:符合 rHu-EPO 适应症的早产儿于 2018 年至 2020 年期间在两家新生儿科住院,其中一家未使用 rHu-EPO,另一家使用了 rHu-EPO。收集了有关新生儿病史、rHu-EPO 和铁治疗以及 pRBCT 适应症和容量的数据。使用反向逻辑回归和 Cox 比例危险度回归对接触和未接触 rHu-EPO 的婴儿进行单变量和多变量分析比较:结果:共纳入 257 名接触过 rHu-EPO 的患者和 285 名未接触过 rHu-EPO 的患者。结果显示了三种情况。在胎龄为讨论期的婴儿中,rHu-EPO对胎儿无益:在我们的队列中未观察到 rHu-EPO 有助于预防 pRBCT。rHu-EPO在未来的应用需要仔细考虑相关人群、调整治疗方案以及pRBCT适应症的演变。
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引用次数: 0
ELP protocol: an original approach for the mitigation of anti-CD38 interference. ELP 协议:缓解抗 CD38 干扰的独创方法。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-06-26 DOI: 10.2450/BloodTransfus.779
Erica Maiorana, Maria Bortolati, Steluta Croitoru, Gledis Llanaj, Cinzia Ongaro, Eva Polga, Melissa Salvo, Alessandra Sandini, Krizia Succoli, Tiziana Tortomasi, Giacomina Vicino, Francesco Fiorin

Background: Transfusion medicine is facing new challenges from therapies which interfere with pre-transfusional tests, such as monoclonal antibodies targeting blood-cell antigens. Anti-CD38 monoclonal antibodies, widely used to treat multiple myeloma, cause panreactivity of indirect antiglobulin test; this can be resolved by treating cells with dithiothreitol to disrupt the CD38 disulphide bonds expressed on red blood cell surfaces. Interference mitigation strategy with dithiothreitol, however, has some drawbacks: it entails losing the traceability of results and the denaturation of blood group systems sensitive to reducing agents; it takes time to perform and quality controls are lost.

Materials and methods: Panels were treated with 0.2 mol/L dithiothreitol and stored for 30 days with a commercial preservative solution. On day 30, we measured the hemolysis indices and ability to eliminate daratumumab and isatuximab interference in the treated cells using indirect antiglobulin test. We also tested the stability of erythrocyte antigenic structure by screening 42 samples with known antibodies; tests were repeated on day 1, 7, 15 and 30. All indirect antiglobulin testing was performed on gel card.

Results: After 30 days from treatment, panels preserved in preservative solution showed hemolysis indices comparable to untreated panels: all cases of interference by anti-CD38 in pre-transfusional tests were successfully mitigated. All antibodies were detected after 30 days, except for KEL system antibodies, as expected, although there was a detectability of anti-Kell antibodies in high titer samples (the first detection in dithiothreitol-treated cells since 1983).

Discussion: We propose the Extended Lifetime Protocol; a simple card-based method which is cheap and traceable, that combines the strengths of anti-CD38 mitigation strategies. It makes it possible to treat and store, at the same time, a sufficient volume of red blood cells, that can be used for the following 30 days, to avoid any delay in transfusional requests.

背景:输血医学正面临着来自干扰输血前检测的疗法(如针对血细胞抗原的单克隆抗体)的新挑战。广泛用于治疗多发性骨髓瘤的抗 CD38 单克隆抗体会导致间接抗球蛋白检测的泛反应性;用二硫苏糖醇处理细胞,破坏红细胞表面表达的 CD38 二硫键,可以解决这一问题。不过,用二硫苏糖醇减轻干扰的策略也有一些缺点:它会使结果失去可追溯性,并使对还原剂敏感的血型系统发生变性;它需要时间来完成,而且会失去质量控制:用 0.2 摩尔/升的二硫苏糖醇处理切片,并用商用防腐剂溶液保存 30 天。第 30 天时,我们使用间接抗球蛋白试验测量了溶血指数以及消除达拉曲单抗和伊沙妥昔单抗对处理细胞干扰的能力。我们还用已知抗体筛选了 42 份样本,以测试红细胞抗原结构的稳定性;测试在第 1、7、15 和 30 天重复进行。所有间接抗球蛋白检测均在凝胶卡上进行:处理 30 天后,在防腐剂溶液中保存的样本溶血指数与未处理的样本溶血指数相当:所有在输血前检测中受抗 CD38 干扰的情况都得到了成功缓解。尽管在高滴度样本中可以检测到抗 Kell 抗体(自 1983 年以来首次在经二硫苏糖醇处理的细胞中检测到),但所有抗体在 30 天后均可检测到,KEL 系统抗体除外:我们提出了 "延长寿命方案",这是一种基于卡片的简单方法,既便宜又可追溯,结合了抗 CD38 缓解策略的优势。它可以同时处理和储存足够数量的红细胞,供接下来的 30 天使用,从而避免输血请求的延误。
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引用次数: 0
Severe aplastic anemia secondary to immune checkpoint inhibitor: case report and literature review. 继发于免疫检查点抑制剂的重型再生障碍性贫血:病例报告和文献综述。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-06-12 DOI: 10.2450/BloodTransfus.723
Alessandro Bosi, Maria C Di Chio, Marta Bortolotti, Giorgio A Croci, Francesco Passamonti, Wilma Barcellini, Bruno Fattizzo
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引用次数: 0
Analysis of HLA matching between deceased organ donors and cord blood units from a national bank network as a basis for potential platforms for chimerism-based immune tolerance after solid organ transplantation. 分析已故器官捐献者与国家血库网络脐带血单位之间的 HLA 匹配情况,为实体器官移植后基于嵌合体的免疫耐受潜在平台奠定基础。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-06-10 DOI: 10.2450/BloodTransfus.759
Roberto Crocchiolo, Letizia Lombardini, Nicoletta Sacchi, Ilaria Lombardi, John Blake, David Allan, Mohamad Sobh, Francesca Puoti, Silvia Trapani, Anna Maria Gallina, Marco Sacchi, Simonetta Pupella, Paola Bergamaschi, Silvano Rossini, Massimo Cardillo
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引用次数: 0
A case of trisomy 9 with mixed-field ABO blood type. 一例 9 三体综合征与 ABO 混合血型。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-06-07 DOI: 10.2450/BloodTransfus.729
Sena Fujii, Yuji Shimura, Keiichi Shigehara, Yuji Sasada, Tohru Inaba
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引用次数: 0
45° Convegno Nazionale di Studi di Medicina Trasfusionale, Rimini, 29-31 maggio 2024. 第 45 届全国输血医学研究大会,里米尼,2024 年 5 月 29-31 日。
IF 3.7 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-05-29 DOI: 10.2450/BloodTransfus.2024.Suppl1
Francesco Fiorin, Patrizia Di Gregorio, Pierluigi Berti, Antonella Matteocci, Giorgio Gandini, Serelina Coluzzi, Renato Messina, Silvano Rossini, Gianluca Ubezio, Domenico Visceglie, Giuseppe Aprili
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引用次数: 0
Natural history of anti-PF 4 antibodies in patients with vaccine-induced immune thrombocytopenia and thrombosis. 疫苗诱发的免疫性血小板减少症和血栓形成患者体内抗 PF4 抗体的自然史。
IF 2.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-05-01 Epub Date: 2024-01-29 DOI: 10.2450/BloodTransfus.544
Elena Lotti, Anna M Gori, Martina Berteotti, Angela Rogolino, Francesca Cesari, Daniela Poli, Francesco Vannini, Alessia Bertelli, Betti Giusti, Rossella Marcucci
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引用次数: 0
期刊
Blood Transfusion
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