Philipp Steininger, Klaus Korn, Holger Hackstein, Erwin F. Strasser
{"title":"Validation of a Parvovirus B19 NAT Assay for Screening of Umbilical Cord Blood for Allogenic Hematopoietic Stem Cell Donation","authors":"Philipp Steininger, Klaus Korn, Holger Hackstein, Erwin F. Strasser","doi":"10.1159/000532073","DOIUrl":"https://doi.org/10.1159/000532073","url":null,"abstract":"<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136241931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"Efficient Chimeric Antigen Receptor T-Cell Generation Starting with Leukoreduction System Chambers of Thrombocyte Apheresis Sets","authors":"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","doi":"10.1159/000532130","DOIUrl":"https://doi.org/10.1159/000532130","url":null,"abstract":"<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136241928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esa Jantunen, Anu Partanen, Antti Turunen, Ville Varmavuo, Raija Silvennoinen
{"title":"Mobilization Strategies in Myeloma Patients Intended for Autologous Hematopoietic Cell Transplantation.","authors":"Esa Jantunen, Anu Partanen, Antti Turunen, Ville Varmavuo, Raija Silvennoinen","doi":"10.1159/000531940","DOIUrl":"https://doi.org/10.1159/000531940","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>Preplanned collection target is important as G-CSF plus plerixafor is more effective in the mobilization of CD34<sup>+</sup> 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.</p><p><strong>Key message: </strong>Currently, G-CSF alone and preemptive plerixafor if needed might be considered as a standard mobilization strategy in MM patients intended for AHCT.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 5","pages":"438-447"},"PeriodicalIF":2.2,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"CD34<sup>+</sup> Cell Mobilization, Autograft Cellular Composition and Outcome in Mantle Cell Lymphoma Patients.","authors":"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","doi":"10.1159/000531799","DOIUrl":"https://doi.org/10.1159/000531799","url":null,"abstract":"<p><strong>Backgound: </strong>Autologous stem cell transplantation (ASCT) is a standard treatment in transplant-eligible mantle cell lymphoma (MCL) patients after first-line chemoimmunotherapy.</p><p><strong>Study design and methods: </strong>This prospective multicenter study evaluated the impact of CD34<sup>+</sup> cell mobilization and graft cellular composition analyzed by flow cytometry on hematologic recovery and outcome in 42 MCL patients.</p><p><strong>Results: </strong>During CD34<sup>+</sup> cell mobilization, a higher blood CD34<sup>+</sup> cell count (>30 × 10<sup>6</sup>/L) was associated with improved overall survival (median not reached [NR] vs. 57 months, <i>p</i> = 0.04). The use of plerixafor did not impact outcome. Higher number of viable cryopreserved graft CD34<sup>+</sup> cells (>3.0 × 10<sup>6</sup>/kg) was associated with faster platelet (median 11 vs. 15 days, <i>p</i> = 0.03) and neutrophil (median 9 vs. 10 days, <i>p</i> = 0.02) recovery posttransplant. Very low graft CD3<sup>+</sup>CD8<sup>+</sup> cell count (≤10 × 10<sup>6</sup>/kg) correlated with worse progression-free survival (PFS) (HR 4.136, 95% CI 1.547-11.059, <i>p</i> = 0.005). On the other hand, higher absolute lymphocyte count >2.5 × 10<sup>9</sup>/L at 30 days after ASCT (ALC-30) was linked with better PFS (median NR vs. 99 months, <i>p</i> = 0.045) and overall survival (median NR in either group, <i>p</i> = 0.05).</p><p><strong>Conclusions: </strong>Better mobilization capacity and higher graft CD3<sup>+</sup>CD8<sup>+</sup> cell count had a positive prognostic impact in this study, in addition to earlier lymphocyte recovery (ALC-30>2.5 × 10<sup>6</sup>/L). These results need to be validated in another study with a larger patient cohort.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 5","pages":"428-437"},"PeriodicalIF":2.2,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quartic CAR-T Cell Bridging to Twice Allo-HSCT Therapy in a Patient with Acute Lymphoblastic Leukemia","authors":"Qing Zhang, Yi Dong, Zhimin Zhai, Qianshan Tao","doi":"10.1159/000531681","DOIUrl":"https://doi.org/10.1159/000531681","url":null,"abstract":"<b><i>Introduction:</i></b> 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. <b><i>Case Presentation:</i></b> 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. <b><i>Conclusion:</i></b> 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.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"2677 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135718096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heiko Lier, Thorsten Annecke, Thierry Girard, Georg Pfanner, Wolfgang Korte, Oliver Tiebel, Dietmar Schlembach, Christian von Heymann
{"title":"Peripartum Haemorrhage: Haemostatic Aspects of the Updated Peripartum Haemorrhage Guideline of the German-Speaking Countries.","authors":"Heiko Lier, Thorsten Annecke, Thierry Girard, Georg Pfanner, Wolfgang Korte, Oliver Tiebel, Dietmar Schlembach, Christian von Heymann","doi":"10.1159/000530659","DOIUrl":"https://doi.org/10.1159/000530659","url":null,"abstract":"<p><strong>Background: </strong>Peripartum haemorrhage (PPH) is a potentially life-threatening complication. Although still rare, the incidence of peripartal haemorrhage is rising in industrialised countries and refractory bleeding remains among the leading causes of death in the peripartal period.</p><p><strong>Summary: </strong>The interdisciplinary German, Austrian, and Swiss guideline on \"Peripartum Haemorrhage: Diagnostics and Therapies\" has reviewed the evidence for the diagnostics and medical, angiographic, haemostatic, and surgical treatment and published an update in September 2022 . This article reviews the updated recommendations regarding the early diagnosis and haemostatic treatment of PPH. Keystones of the guideline recommendations are the early diagnosis of the bleeding by measuring blood loss using calibrated collector bags, the development of a multidisciplinary treatment algorithm adapted to the severity of bleeding, and the given infrastructural conditions of each obstetric unit, the early and escalating use of uterotonics, the therapeutic, instead of preventative, use of tranexamic acid, the early diagnostics of progressive deficiencies of coagulation factors or platelets to facilitate a tailored and guided haemostatic treatment with coagulation factors, platelets as well as packed red blood cells and fresh frozen plasma when a massive transfusion is required.</p><p><strong>Key messages: </strong>Essential for the effective and safe treatment of PPH is the timely diagnosis. The diagnosis of PPH requires the measurement rather than estimation of blood loss. Successful treatment of PPH consists of a multidisciplinary approach involving surgical and haemostatic treatments to stop the bleeding. Haemostatic treatment of PPH starts early after diagnosis and combines tranexamic acid, an initially ratio-driven transfusion with RBC:plasma:PC = 4:4:1 (when using pooled or apheresis PC) and finally a goal-directed substitution with coagulation factor concentrates for proven deficiencies. Early monitoring of coagulation either by standard parameters or viscoelastic methods facilitates goal-directed haemostatic treatment.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 6","pages":"547-558"},"PeriodicalIF":2.2,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10712975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandra Sauer, Lennart Hieke, Juliane Brandt, Carsten Müller-Tidow, Anita Schmitt, Joseph Kauer, Katharina Kriegsmann
{"title":"Impact of Clinical Parameters and Induction Regimens on Peripheral Blood Stem-Cell Mobilization and Collection in Multiple Myeloma Patients.","authors":"Sandra Sauer, Lennart Hieke, Juliane Brandt, Carsten Müller-Tidow, Anita Schmitt, Joseph Kauer, Katharina Kriegsmann","doi":"10.1159/000530056","DOIUrl":"https://doi.org/10.1159/000530056","url":null,"abstract":"<p><strong>Introduction: </strong>High-dose chemotherapy (HDCT) followed by autologous blood stem-cell transplantation (ABSCT) remains the standard consolidation therapy for newly diagnosed eligible multiple myeloma (MM) patients. As a prerequisite, peripheral blood stem cells (PBSCs) must be mobilized and collected by leukapheresis (LP). Many factors can hamper PBSC mobilization/collection. Here, we provide a comprehensive multiparametric assessment of PBSC mobilization/collection outcome parameters in a large cohort.</p><p><strong>Methods: </strong>In total, 790 MM patients (471 [60%] male, 319 [40%] female) who underwent PBSC mobilization/collection during first-line treatment were included. Evaluated PBSC mobilization/collection outcome parameters included the prolongation of PBSC mobilization, plerixafor administration, number of LP sessions, and overall PBSC collection goal/result.</p><p><strong>Results: </strong>741 (94%) patients received cyclophosphamide/adriamycin/dexamethasone (CAD) and granulocyte-colony-stimulating factor (G-CSF) mobilization. Plerixafor was administered in 80 (10%) patients. 489 (62%) patients started LP without delay. 530 (67%) patients reached the PBSC collection goal at the first LP session. The mean overall PBSC collection result was 10.3 (standard deviation [SD] 4.4) × 10<sup>6</sup> CD34<sup>+</sup> cells/kg. In a multiparametric analysis, variables negatively associated with PBSC mobilization/collection outcomes were female gender, age >60 years, an advanced ISS stage, and local radiation pre-/during induction, but not remission status postinduction. Notably, the identified risk factors contributed differently to each PBSC mobilization/collection outcome parameter. In this context, compared to all other induction regimens, lenalidomide-based induction with/without antibodies negatively affected only the number of LP sessions required to reach the collection goal, but no other PBSC mobilization/collection outcome parameters. In contrast, the probability of reaching a high collection goal of ≥6 × 10<sup>6</sup> CD34<sup>+</sup> cells/kg body weight was higher after lenalidomide-based induction compared to VCD/PAD or VAD - taking into account - that a higher G-SCF dosage was given in approximately one-third of patients receiving lenalidomide-based induction with/without antibodies.</p><p><strong>Conclusion: </strong>Considering the identified risk factors in the clinical setting can contribute to optimized PBSC mobilization/collection. Moreover, our study demonstrates the necessity for a differentiated evaluation of PBSC mobilization/collection outcome parameters.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 5","pages":"382-395"},"PeriodicalIF":2.2,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Norbert Niklas, Claudia Loimayr, Julia Lenz, Susanne Süßner, Gerhard Schuster, David Jungwirth, Werner Watzinger, Stephan Federsel
{"title":"The Impact of Digital Transformation on Blood Donation and Donor Characteristics.","authors":"Norbert Niklas, Claudia Loimayr, Julia Lenz, Susanne Süßner, Gerhard Schuster, David Jungwirth, Werner Watzinger, Stephan Federsel","doi":"10.1159/000530270","DOIUrl":"https://doi.org/10.1159/000530270","url":null,"abstract":"<p><strong>Introduction: </strong>The management of an adequate donor pool is a constant and challenging task for blood centers in order to provide blood supply. New methods are required to streamline processes and attract (new) donors on a sustained basis. We present a digitalization method without media disruption and show the impact on our donors and their behavior.</p><p><strong>Methods: </strong>We designed and created a blood donation app that is fully compliant to all regulations and conforms to donor expectations. The presented digitalization serves the donor from preparation before the donation (health questionnaire) until completion of laboratory testing (medical report). Many other features are included and continuously attract donors to engage with the blood donation topic.</p><p><strong>Results: </strong>Eighteen months after the launch of our app, there are already 45,000 users. The digital questionnaire reduced the number of deferrals by 31.9% compared to the conventional paper questionnaire. Digital adopters show a significantly shorter donation interval (193 days compared to 316 days). In-app incentives include identification card, rapid laboratory testing results (time-to-results are two business days for 95%), and collection of badges among others.</p><p><strong>Conclusion: </strong>The presented method has changed our donor pool. Besides that, medical staff benefits from the automated process that allows focusing on the donor and their admission. On the other hand, the app has become a valid tool to manage our donor pool and attract first-time and young donors.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 6","pages":"531-538"},"PeriodicalIF":2.2,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10712983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingfu Liu, Shan Chen, Zhen Li, Rong Lu, Xianren Ye
{"title":"Different Expression Profiles of Exosomal circRNAs from Apheresis Platelets during Storage.","authors":"Jingfu Liu, Shan Chen, Zhen Li, Rong Lu, Xianren Ye","doi":"10.1159/000530040","DOIUrl":"https://doi.org/10.1159/000530040","url":null,"abstract":"<p><strong>Introduction: </strong>Bioactive substances of stored platelets change during the stored periods. Exosomes are reported to be increased during platelet storage. Circular RNAs (circRNAs) are one of the main components in exosomes. It is the purpose of this study to investigate the different expression of exosomal circRNAs during storage.</p><p><strong>Methods: </strong>Apheresis platelets were collected from 7 healthy volunteers and stored in platelet storage bags for 1 day or 5 days. We isolated exosomes by ultracentrifugation and characterized exosomes by transmission electron microscopy, nano-flow cytometry, and Western blot. We conducted microarray analysis to detect changes in the exosomal circRNAs from apheresis platelets during storage, and qRT-PCR to validate their expressions. To analyze the competing endogenous RNA (ceRNA) of circRNAs, microRNAs (miRNAs) targets were predicted based on interactions of circRNAs/miRNAs and miRNAs/mRNAs, using TargetScan and miRanda. A ceRNA network was constructed by Cytoscape. The targeted mRNAs were performed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis by the DAVID.</p><p><strong>Results: </strong>Microarray analysis revealed that 61 differentially expressed circRNAs between day 1 and day 5. Thirty-one circRNAs of these are upregulated, while 30 circRNAs are downregulated. A ceRNA visualized network includes 9 circRNAs, 48 miRNAs, and 117 mRNAs. There were 117 mRNAs enriched in 203 GO terms and 9 KEGG pathways based on the GO and KEGG pathway enrichment analyses.</p><p><strong>Conclusion: </strong>We identified 61 dysregulated exosomal circRNAs from apheresis platelets during storage. The study provided insights into the underlying mechanisms of platelet storage lesion.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 6","pages":"515-524"},"PeriodicalIF":2.2,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10712982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liron Miller, Mor Freed-Freundlich, Avichai Shimoni, Tamer Hellou, Abraham Avigdor, Mudi Misgav, Jonathan Canaani
{"title":"Defining Current Patterns of Blood Product Use during Intensive Induction Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia Patients.","authors":"Liron Miller, Mor Freed-Freundlich, Avichai Shimoni, Tamer Hellou, Abraham Avigdor, Mudi Misgav, Jonathan Canaani","doi":"10.1159/000529595","DOIUrl":"https://doi.org/10.1159/000529595","url":null,"abstract":"<p><strong>Introduction: </strong>Blood product transfusion retains a critical role in the supportive care of patients with acute myeloid leukemia (AML). Whereas previous studies have shown increased transfusion dependency to portend inferior outcome, predictive factors of an increased transfusion burden and the prognostic impact of transfusion support have not been assessed recently.</p><p><strong>Methods/patients: </strong>We performed a retrospective analysis on a recent cohort of patients given intensive induction chemotherapy in 2014-2022.</p><p><strong>Results: </strong>The analysis comprised 180 patients with a median age of 57 years with 80% designated as de novo AML. Fifty-four patients (31%) were <i>FLT3-ITD</i> mutated, and 73 patients (42%) harbored <i>NPM1</i>. Favorable risk and intermediate risk ELN 2017 patients accounted for 43% and 34% of patients, respectively. The median number of red blood cell (RBC) and platelet units given during induction were 9 and 7 units, respectively. Seventeen patients (9%) received cryoprecipitate, and fresh frozen plasma (FFP) was given to 12 patients (7%). Lower initial hemoglobin and platelet levels were predictive of increased use of RBC (<i>p</i> < 0.0001) and platelet transfusions (<i>p</i> < 0.0001). FFP was significantly associated with induction related mortality (42% vs. 5%; <i>p</i> < 0.0001) and with <i>FLT3-ITD</i> (72% vs. 28%; <i>p</i> = 0.004). Blood group AB experienced improved mean overall survival compared to blood group O patients (4.1 years vs. 2.8 years; <i>p</i> = 0.025). In multivariate analysis, increased number of FFP (hazard ratio [HR], 4.23; 95% confidence interval [CI], 2.1-8.6; <i>p</i> < 0.001) and RBC units (HR, 1.8; 95% CI, 1.2-2.8; <i>p</i> = 0.008) given was associated with inferior survival.</p><p><strong>Conclusion: </strong>Transfusion needs during induction crucially impact the clinical trajectory of AML patients.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"50 5","pages":"456-468"},"PeriodicalIF":2.2,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}