Pub Date : 2024-07-01DOI: 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。
{"title":"Anti-CD38 monoclonal antibody impairs CD34+ mobilization and affects clonogenic potential in multiple myeloma patients.","authors":"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","doi":"10.2450/BloodTransfus.667","DOIUrl":"10.2450/BloodTransfus.667","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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 3.98×10<sup>6</sup>/kg (range 1.68-9.18) vs 6.87×10<sup>6</sup>/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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":49260,"journal":{"name":"Blood Transfusion","volume":" ","pages":"328-337"},"PeriodicalIF":2.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 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.
{"title":"The role of erythropoietin to prevent red blood cell transfusion in a 2018-2020 two-center cohort of preterm infants.","authors":"Noémie Bailly, Roselyne Brat, Geraldine Favrais","doi":"10.2450/BloodTransfus.641","DOIUrl":"10.2450/BloodTransfus.641","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":49260,"journal":{"name":"Blood Transfusion","volume":" ","pages":"303-311"},"PeriodicalIF":2.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-26DOI: 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.
{"title":"ELP protocol: an original approach for the mitigation of anti-CD38 interference.","authors":"Erica Maiorana, Maria Bortolati, Steluta Croitoru, Gledis Llanaj, Cinzia Ongaro, Eva Polga, Melissa Salvo, Alessandra Sandini, Krizia Succoli, Tiziana Tortomasi, Giacomina Vicino, Francesco Fiorin","doi":"10.2450/BloodTransfus.779","DOIUrl":"https://doi.org/10.2450/BloodTransfus.779","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":49260,"journal":{"name":"Blood Transfusion","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-12DOI: 10.2450/BloodTransfus.723
Alessandro Bosi, Maria C Di Chio, Marta Bortolotti, Giorgio A Croci, Francesco Passamonti, Wilma Barcellini, Bruno Fattizzo
{"title":"Severe aplastic anemia secondary to immune checkpoint inhibitor: case report and literature review.","authors":"Alessandro Bosi, Maria C Di Chio, Marta Bortolotti, Giorgio A Croci, Francesco Passamonti, Wilma Barcellini, Bruno Fattizzo","doi":"10.2450/BloodTransfus.723","DOIUrl":"https://doi.org/10.2450/BloodTransfus.723","url":null,"abstract":"","PeriodicalId":49260,"journal":{"name":"Blood Transfusion","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-10DOI: 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
{"title":"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.","authors":"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","doi":"10.2450/BloodTransfus.759","DOIUrl":"https://doi.org/10.2450/BloodTransfus.759","url":null,"abstract":"","PeriodicalId":49260,"journal":{"name":"Blood Transfusion","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-29DOI: 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
{"title":"45° Convegno Nazionale di Studi di Medicina Trasfusionale, Rimini, 29-31 maggio 2024.","authors":"Francesco Fiorin, Patrizia Di Gregorio, Pierluigi Berti, Antonella Matteocci, Giorgio Gandini, Serelina Coluzzi, Renato Messina, Silvano Rossini, Gianluca Ubezio, Domenico Visceglie, Giuseppe Aprili","doi":"10.2450/BloodTransfus.2024.Suppl1","DOIUrl":"https://doi.org/10.2450/BloodTransfus.2024.Suppl1","url":null,"abstract":"","PeriodicalId":49260,"journal":{"name":"Blood Transfusion","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-01-29DOI: 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
{"title":"Natural history of anti-PF 4 antibodies in patients with vaccine-induced immune thrombocytopenia and thrombosis.","authors":"Elena Lotti, Anna M Gori, Martina Berteotti, Angela Rogolino, Francesca Cesari, Daniela Poli, Francesco Vannini, Alessia Bertelli, Betti Giusti, Rossella Marcucci","doi":"10.2450/BloodTransfus.544","DOIUrl":"10.2450/BloodTransfus.544","url":null,"abstract":"","PeriodicalId":49260,"journal":{"name":"Blood Transfusion","volume":" ","pages":"246-252"},"PeriodicalIF":2.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11073623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}