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1.
Transfus Apher Sci ; 62(6): 103831, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37827962

RESUMEN

The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs). MATERIAL AND METHODS: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.org RESULTS: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018-2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0-94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%). CONCLUSION: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.


Asunto(s)
Eliminación de Componentes Sanguíneos , Humanos , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Eliminación de Componentes Sanguíneos/métodos , Intercambio Plasmático/efectos adversos , Plasmaféresis , Sistema de Registros , Donantes de Tejidos
2.
J Clin Apher ; 38(2): 77-278, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37017433

RESUMEN

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. In the Ninth Edition, the JCA Special Issue Writing Committee has incorporated systematic review and evidence-based approaches in the grading of evidence and categorization of apheresis indications to make recommendations on the use of apheresis in a wide variety of diseases and conditions. This edition has largely maintained the general layout and concept of a fact sheet introduced in the Fourth Edition (2007). Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease or medical condition. The Ninth Edition of the JCA Special Issue comprises 91 fact sheets and 166 graded and categorized indications. This includes seven new fact sheets, nine new indications on existing fact sheets, and eight changes in the category for existing indications. The Ninth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.


Asunto(s)
Eliminación de Componentes Sanguíneos , Medicina Basada en la Evidencia , Humanos , Estados Unidos , Escritura
3.
Pediatr Hematol Oncol ; 40(2): 181-191, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35848787

RESUMEN

Venous thromboembolism (VTE) is a well-known complication of the treatment of pediatric acute lymphoblastic leukemia (ALL). We analyzed 1026 ALL patients 1-18-years-old, who were enrolled into the AIEOP-BFM ALL 2000 or 2009 studies in Austria, with regard to the incidence and risk factors of VTE. The 2.5-year cumulative incidence (CI) of VTE ≥ grade 2 was 4%±1% (n = 36/1026). Twenty VTE (56%) were found in the central nervous system (19 cerebral venous sinus and 1 cortical vein thrombosis), and 16 (44%) at other sites (7 deep vein thromboses (DVT) of the lower extremity, 4 DVT of the upper extremity, 4 central venous line-thromboses, 1 pulmonary embolism). Most VTE occurred during induction and early consolidation therapy (81%) and were associated with L-asparaginase within 4 and corticosteroids withing 1 week(s) preceding the event (89 and 86%, respectively). In multivariable analysis, two independent risk factors were found. Patients 10-18-years-old had an increased (hazard-ratio: 2.156, p = 0.0389), whereas treatments in trial AIEOP-BFM ALL 2009 had a lower risk for VTE (hazard-ratio: 0.349, p = 0.0270). In conclusion, the 2.5-year CI of VTE among our pediatric patient cohort was <5% and adolescent age was the main patient-related risk factor. This older age group might benefit from primary prophylactic measures.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Trombosis Venosa Profunda de la Extremidad Superior , Tromboembolia Venosa , Adolescente , Niño , Humanos , Anciano , Lactante , Preescolar , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Incidencia , Austria/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Factores de Riesgo
4.
J Clin Apher ; 36(6): 878-881, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34510542

RESUMEN

Since vaccination for SARS-CoV-2 coronavirus started, the trajectory of patient numbers infected with the virus has improved once; however, variants of SARS-CoV-2 have emerged and more people have been infected; therefore, pandemic status is still far from resolution. Government and social efforts to prevent coronavirus infection continue in most states in the US and globally even after the Centers for Disease Control and Prevention declared some restriction relief for fully vaccinated people in March 2021. Healthcare institutions and various professional organizations have developed guidelines or policies to prevent the spread of these coronaviruses in the setting of apheresis. In this report, the issues that apheresis services may encounter under the current COVID-19 (SARS-CoV-2 coronavirus disease) pandemic will be discussed with potential strategies that can be adapted for efficient and optimum use of apheresis resources.


Asunto(s)
Eliminación de Componentes Sanguíneos , COVID-19/epidemiología , Pandemias , Eliminación de Componentes Sanguíneos/métodos , Eliminación de Componentes Sanguíneos/estadística & datos numéricos , Humanos , Guías de Práctica Clínica como Asunto , SARS-CoV-2 , Sociedades Médicas , Estados Unidos/epidemiología
5.
Transfus Med Hemother ; 48(4): 234-239, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34539317

RESUMEN

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

6.
J Clin Apher ; 35(5): 493-499, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32770558

RESUMEN

Since 1986, the American Society for Apheresis (ASFA) has published practice guidelines on the use of therapeutic apheresis in the Journal of Clinical Apheresis (JCA) Special Issue. Since 2007, updated guidelines have been published every 3 years to reflect current evidence based apheresis practice with the most recent edition (8th) published in 2019. With each edition, the guidelines are reviewed and updated based on any newly published literature since the last review. The PEXIVAS study, an international, randomized controlled trial comparing therapeutic plasma exchange (TPE) vs no TPE and standard vs reduced dose steroid regimen on the primary composite outcome of end stage renal disease or death in patients with ANCA-associated vasculitis (AAV), was published in February 2020. This study represents the largest study on the role of therapeutic apheresis in AAV published to date and prompted the JCA Special Issue Writing Committee to reassess the current AAV fact sheet for updates based on this newly available evidence. This interim fact sheet summarizes current ASFA recommendations for the evidence-based use of therapeutic apheresis in AAV and supersedes the recommendations published in the 2019 guidelines.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Eliminación de Componentes Sanguíneos/métodos , Guías de Práctica Clínica como Asunto , Humanos , Intercambio Plasmático , Sociedades Médicas
7.
Transfus Apher Sci ; 63(2): 103889, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38388335
8.
J Clin Apher ; 34(3): 171-354, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31180581

RESUMEN

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.


Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Medicina Basada en la Evidencia/normas , Humanos , Terapéutica/métodos , Estados Unidos , Escritura
9.
Vox Sang ; 113(7): 632-638, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30079964

RESUMEN

BACKGROUND AND OBJECTIVES: Symptomatic hypocalcaemia is common during apheresis procedures based on citrate-based anticoagulants. As a consequence, patients often receive prophylactic calcium treatment. However, a recent publication based on the World Apheresis Association (WAA) register suggested harmful effects of such prophylactic calcium use. Recognizing possible limitations in the previous WAA register analyses, we critically re-evaluate the data, to test whether a change in prophylactic calcium usage may be warranted. MATERIALS AND METHODS: Using the WAA register, we reanalysed previous data by means of centre and treatment type stratification, to explore the role of prophylactic calcium as a risk factor for adverse events. RESULTS: There was large variability in adverse event rates dependent on the centre performing the apheresis procedure and dependent on the type of procedure. When this variability was accounted for, there was no clear effect of calcium administration on risk of adverse effects. CONCLUSION: Shortcomings in the previous WAA register analyses may have failed to account for important confounding factors resulting in a substantial overestimation of the risk attributable to calcium usage. Overall our findings do not support a negative effect of prophylactic calcium administration in the apheresis setting.


Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Calcio/efectos adversos , Sistema de Registros , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
10.
Biol Blood Marrow Transplant ; 23(7): 1128-1133, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28359910

RESUMEN

Veno-occlusive disease (VOD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prophylactic use of defibrotide (DF) might further reduce VOD rates but has no impact on the incidence of severe VOD or VOD-associated mortality. We investigated the cost-effectiveness of prophylactic DF according to the British Committee for Standards in Haematology/British Society for Blood and Marrow Transplantation guidelines in 348 children who underwent transplantation between 2001 and 2014 in our hospital, 138 of whom were at risk for VOD. The VOD incidence was 7.4% for the total cohort. Patients at risk had a higher incidence of VOD compared with patients without risk factors (15.2% versus 2.4%, P < .0001). VOD occurred more often in patients after busulfan-based myeloablative conditioning than in patients after total body irradiation (11.2% versus 3.5%, P = .001). Donor types or the transplantation-related mortality (TRM) risk score did not correlate with VOD incidence. In 81% of patients who responded to therapeutic DF, VOD resolved completely. Overall VOD-associated mortality was .3% for the complete cohort, 3.7% for patients diagnosed with VOD, and 20% for patients with severe VOD. Neither the cumulative incidence of TRM (19% ± 8% versus 17% ± 2%, P = .706) nor the median length of hospitalization differed between patients with VOD and patients without. The median costs per HSCT in patients with VOD were about one-third higher than the overall median costs per transplantation at our institution. The calculated total costs of prophylactic DF treatment for 138 patients at risk was almost 6 times as high as the incremental costs for patients with VOD. We conclude that prophylactic DF for children at risk for VOD is not cost-effective with respect to TRM and length of hospital stay.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/economía , Polidesoxirribonucleótidos/economía , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adolescente , Adulto , Niño , Preescolar , Análisis Costo-Beneficio , Femenino , Enfermedad Veno-Oclusiva Hepática/patología , Humanos , Lactante , Recién Nacido , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Polidesoxirribonucleótidos/uso terapéutico , Adulto Joven
11.
Transfus Apher Sci ; 56(1): 59-65, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28188006

RESUMEN

BACKGROUND: Therapeutic plasma exchange (TPE) is a generally accepted and frequently performed procedure for numerous therapeutic indications in adults. Slowly, TPE is also becoming more and more popular in the treatment of pediatric patients. Although, we know that TPE is safe in pediatric patients, the outcome of children treated with TPE is rarely reported. Furthermore, there are only general recommendations regarding the plasma replacement fluid for children and these are adopted from adults. Data concerning outcome and the influence of different types of replacement fluids on hemostasis in children are scarce. METHODS: We retrospectively evaluated 324 TPE treatments performed in 35 patients between 2008 and 2013 in our level 4 institution for pediatric hematology and oncology. The plasmapheresis procedures were categorized into three groups based on the replacement fluid used. The first group received solvent/detergent-treated (S/D) plasma (70.0% of patients), the second group was administered 5% human albumin (7.7% of patients) and the third group was treated with a combination of human albumin 5% and S/D plasma (22.3% of patients). To assess hemostasis, data on INR, aPTT, fibrinogen and ATIII were collected before and after plasmapheresis from the patients' charts. A modified Multi Organ Dysfunction Syndrome (MODS) Index was used to classify organ failure. Patient outcome, survival rate and adverse events were evaluated. RESULTS: We found a significant increase in the INR by 35.83% and of the aPTT by 18.53% within the human albumin group. The INR and aPTT of patients allocated to the S/D plasma group decreased by 1.58% and 15.77% on average, respectively. The combination group revealed a mild increase of the INR (9.47%), accompanied by a reduction of aPTT (5.97%). Furthermore we found that the survival rate was significantly associated with a MODS Index of <2 (p<0.001). Overall, the number of adverse events was low (1.2%) and none of these were considered life-threatening. CONCLUSION: Hemostasis could be preserved in a clinically acceptable range for a variety of underlying diseases with SD plasma alone or in combination with human albumin. Based on our results we would recommend practitioners to closely pre-estimate the hemostatic situation before using human albumin alone in critically ill pediatric patients with a limited ability to produce coagulation factors. The outcome of the patients in our collective exprience is correlated to the extent of organ dysfunction. Therefore further controlled studies are highly recommended.


Asunto(s)
Hemostasis/fisiología , Sustitutos del Plasma/administración & dosificación , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
12.
Transfus Apher Sci ; 56(1): 39-44, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28089410

RESUMEN

Microparticles have been shown to shed from a variety of viable cells as a consequence of inflammatory processes, activation or physical stress. Seventy to 90% of circulating microparticles are thought to be platelet-derived. The content of microparticles in blood collected from normal blood donors is highly variable and transfers into the final blood component. Elevated microparticle content (MPC) in donor blood might indicate an asymptomatic clinical condition of the donor which might affect the transfusion recipient, particularly pediatric patients. ThromboLUX is a new technology designed to routinely test biological samples for microparticle content. We compared MPC in platelet-rich plasma (PRP) of apheresis donors and the corresponding INTERCEPT-treated apheresis products (N=24). The MPCs in donor and product samples were correlated (r=0.74, P<0.001). Microparticles were significantly reduced after plasma replacement and INTERCEPT treatment. These findings are supported by phase contrast microscopy. Platelet transfusions given to patients with fever or systemic inflammation are less efficacious. In addition, transfusing heterogeneous platelets - concentrates with high MPC and activated platelets - to patients whose immune systems are activated might tip them over a threshold and cause platelet refractoriness. Restricting prophylactic platelet transfusions to homogeneous products - concentrates with resting platelets and therefore low MPC - may reduce the risk of refractoriness in cancer patients, especially children with immature immunity. To test this hypothesis we introduce an evaluation protocol for platelet management, i.e., keeping a split inventory of homogeneous and heterogeneous platelets, and using only homogeneous platelets for prophylaxis as a strategy to reduce refractoriness.


Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Medicina Transfusional/métodos , Adolescente , Niño , Preescolar , Humanos , Transfusión de Plaquetas/métodos
13.
Biol Blood Marrow Transplant ; 22(1): 96-103, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26307344

RESUMEN

Related donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation.


Asunto(s)
Discusiones Bioéticas , Selección de Donante/ética , Selección de Donante/métodos , Trasplante de Células Madre Hematopoyéticas/ética , Trasplante de Células Madre Hematopoyéticas/métodos , Donantes de Tejidos/ética , Adolescente , Aloinjertos , Niño , Preescolar , Femenino , Humanos , Masculino , Guías de Práctica Clínica como Asunto
14.
Transfus Apher Sci ; 55(2): 221-224, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27452644

RESUMEN

For successful bone marrow transplantation it is necessary to obtain enough progenitor cells during the bone marrow (BM) harvesting procedure. Most centers are using multiple aspirations of maximum 2 ml BM (A), while other centers are using few larger amount aspirations for BM harvesting (B). There is still a discussion about possible differences in graft composition between A and B. To evaluate the feasibility in children we evaluated twenty BM harvestings that were performed in 18 donors, 7 autologous (median age 6.93y; 2.48-16.6) and 13 allogeneic donors (median age 19.75y; 6.45-50.7). A and B were performed crosswise by 2 operators starting with A (2 ml) or B (100 ml) changing to B or A, collecting identically amounts with both methods. We found no statistically significant difference between A and B for MNC, T-cells, and CFU (MNC/ml 824572 versus 725000, p = 0.728; MNC/kg 3.1 107 versus 2.9 107, p = 0.296; CD3/ml 162500 versus 300000, p = 0.310; CFU/105 MNC 1678 versus 1315, p = 0.094), but for CD34+ cells (CD34/kg 2.62 versus 2.09, p = 0.045). BM harvest by the large amount few punctures method (B) is as sufficient as the commonly used small amount frequent punctures method (A), and could be therefore used equally.


Asunto(s)
Trasplante de Médula Ósea/métodos , Médula Ósea , Paracentesis/métodos , Donantes de Tejidos , Adolescente , Adulto , Aloinjertos , Autoinjertos , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
J Clin Apher ; 31(3): 149-62, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27322218

RESUMEN

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Medicina Basada en la Evidencia/normas , Guías de Práctica Clínica como Asunto , Humanos , Sociedades Médicas
16.
Cytotherapy ; 17(7): 989-1007, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25866178

RESUMEN

BACKGROUND AIMS: Despite antiviral drug therapies, human adenovirus (HAdV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections still contribute substantially to transplant-related death of patients after hematopoietic stem cell transplantation. Earlier clinical studies demonstrated successful adoptive transfer of magnetically selected CMV-specific T cells via removable, and thus Good Manufacturing Practice-compliant, major histocompatibility class I streptamers. Thus, the primary focus of the present study was the selection of HAdV-streptamer+ T cells, although in three experiments, EBV-streptamer+ T cells were also selected. METHODS: Cells from leukaphereses of healthy donors were prepared in large (1-6 × 10(9)) and small (25 × 10(6)) cell batches. Whereas the larger batch was directly labeled with streptamers to select HAdV- and/or EBV-specific T cells (large-scale), the smaller batch was used to generate in vitro virus-specific T-cell lines before streptamer labeling for streptamer selection (small-scale). Isolation of HAdV- and/or EBV-specific T cells was performed with the use of the CliniMACS device. RESULTS: The purity of HAdV- and EBV-streptamer+ T cells among CD3+ cells, obtained from large-scale selection, was up to 6.7% and 44%, respectively. If HAdV- and EBV-streptamers were applied simultaneously, the purity of antigen-specific T cells reached up to 50.7%. A further increase in purity reaching up to 98% was achieved by small-scale selection of HAdV-specific T cells. All final products fulfilled the microbiological and chemical release criteria. Interferon-γ-response indicating functional activity was seen in 6 of 9 HAdV and 2 of 3 EBV large-scale selections and in 2 of 3 HAdV small-scale selections. CONCLUSIONS: HAdV-streptamers were shown to be clinically feasible for few patients after the large-scale approach but for larger patient numbers if combined with EBV-streptamers or after the small-scale approach.


Asunto(s)
Adenovirus Humanos/inmunología , Citomegalovirus/inmunología , Herpesvirus Humano 4/inmunología , Coloración y Etiquetado/métodos , Linfocitos T/inmunología , Infecciones por Adenoviridae/inmunología , Traslado Adoptivo , Infecciones por Citomegalovirus/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Interferón gamma/inmunología , Activación de Linfocitos/inmunología , Masculino
17.
Biol Blood Marrow Transplant ; 20(5): 676-83, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24492145

RESUMEN

Although the influence of transplanted bone marrow (BM) CD34+ cells on neutrophil engraftment (NE) and transplantation outcomes has been discussed controversially, thresholds between 2 and 4 × 10(6)/kg CD34+ cells are commonly accepted. This has substantial consequences for a donor in terms of BM volume to be collected, which frequently covers up to 15 to 20 mL/kg. As the BM CD34+ compartment contains varying fractions of CD34+/CD19+ B lymphoid progenitors, we tested the hypothesis that the infused CD34+/CD45dim/CD19-/CD10- myeloid stem cells might reliably predict NE in 94 children who received BM from 37 HLA-identical sibling donors (MSD) and 57 matched unrelated donors after myeloablative conditioning. The grafts contained a median of 3.6 × 10(6)/kg total CD34+ cells, which consisted of a median of 73% myeloid CD34+ cells and 27% B lymphoid progenitors. Grafts from donors <15 years old yielded significantly lower myeloid fractions compared with grafts from older donors (P < .001). All patients achieved sustained NE after median 20 (range, 11 to 40) days. By multivariate analysis, neither the number of total CD34+ cells (P = .605) nor of myeloid CD34+ cells (P = .981) correlated with NE, whereas transplantation from MSD (hazard ratio [HR] 3.51; P = .019) and the administration of granulocyte colony-stimulating factor (HR 2.24; P = .002) remained independent factors associated with earlier NE. Furthermore, neither total nor myeloid CD34+ cell quantities were associated with incidences of severe infections before NE (P = .271 and P = .132) or transplantation-related mortality (TRM) at day +100 (P = .294 and P = .490). Taking into account that the number of transplanted total CD34+ or myeloid CD34+ cells does not seem to have a relevant impact on time to NE, sepsis rates, or TRM, the need of certain threshold cell numbers should be revisited, at least for pediatric MSD.


Asunto(s)
Linfocitos B/inmunología , Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped/terapia , Neoplasias Hematológicas/terapia , Neutrófilos/inmunología , Acondicionamiento Pretrasplante , Adolescente , Antígenos CD34/inmunología , Linfocitos B/patología , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Prueba de Histocompatibilidad , Humanos , Lactante , Recuento de Linfocitos , Masculino , Agonistas Mieloablativos/uso terapéutico , Neutrófilos/citología , Estudios Prospectivos , Hermanos , Análisis de Supervivencia , Donantes de Tejidos , Trasplante Homólogo , Adulto Joven
18.
J Clin Apher ; 28(6): 411-5, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24000045

RESUMEN

Erythrocyte-exchange (EEX) has proven to be a very useful tool in sickle-cell disease (SCD) patients either during acute painful crisis unresponsive to hydration and/or analgesia or as a prophylactic treatment in high risk patients in those who do not tolerate hydroxyurea (HU), with the aim of lowering HbS levels. EEX may be performed either by using continuous- or discontinuous flow devices, the former being of choice in children or in low-weight patients. Thus, a low extracorporeal blood volume (EBV) could allow for a better and safer procedure management. In this study we compared EEX procedure performed with the recently released OPTIA device with EEX procedures performed using the COBE Spectra device (EBV 185 vs 270 mL, respectively). Twenty-one EEX (4 as emergency treatment) were performed in 12 patients with the Spectra device and 25 (9 as emergency treatment) in 15 patients with the OPTIA device. All the procedures were well tolerated and uneventful. We did not observe significant differences between the two devices as to pre- and post-EEX parameters, namely in target hematocrit and in HbS reduction. Noteworthy, due to the lowest EBV allowed by the OPTIA device, an EEX procedure performed in a 13 Kg- child did not require a preliminary priming of the circuit. In conclusion, the OPTIA device proved to be as effective as the Spectra device in treating SCD patients either during sickling crisis or as prophylactic therapy. The OPTIA device can be safely used in the pediatric setting since it allows a lower EBV.


Asunto(s)
Anemia de Células Falciformes/terapia , Citaféresis/instrumentación , Transfusión de Eritrocitos/métodos , Citometría de Flujo/métodos , Adulto , Anemia de Células Falciformes/sangre , Recuento de Células Sanguíneas , Volumen Sanguíneo , Peso Corporal , Citaféresis/métodos , Urgencias Médicas , Diseño de Equipo , Femenino , Humanos , Masculino , Adulto Joven
19.
Blood Transfus ; 21(5): 378-384, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36346886

RESUMEN

BACKGROUND: Substantial regional differences in the genetic patterns related to blood group have been observed across different continents. This diversity means that the blood supply, as an essential part of patient care, is increasingly impacted by global migration. Consequently, the Austrian blood donor population does not match the immigrant patient population. This mismatch is likely to result in the formation of alloantibodies to red cell antigens in the chronically transfused. Subsequently, major difficulties in providing compatible blood emerge. MATERIAL AND METHODS: The study included patients of African origin (n=290) and Caucasians who represent the Austrian donor population (n=1,017). Genetic typing was performed for up to 69 blood group polymorphisms with a multiplex sequence specific primer-PCR including high frequency antigens and antigens for which antisera are not commercially available. By assessing differences in antigen frequencies between the two populations, and using these data for prophylactic matching, we aim to develop tools to increase the quality of patient care. RESULTS: Results indicate various and significant differences (p<0.0001) in antigen frequencies between African patients and the European donor population, especially in the MNS, Duffy, Knops and Rhesus systems. DISCUSSION: Our data highlight the importance of matching the donor population to the demographics of the patient population. In addition, it underlines the need to recruit donors of African origin and to focus on the upcoming challenges, such as malaria semi-immunity and a significantly higher rate of infectious disease in this population. It is also recommended to apply extended genetic typing to detect rare blood types, and (cryo)storage of rare blood in national and international rare blood banks. Co-operation with regional blood banks should also be encouraged.


Asunto(s)
Antígenos de Grupos Sanguíneos , Humanos , Antígenos de Grupos Sanguíneos/genética , Polimorfismo Genético , Isoanticuerpos/genética , Bancos de Sangre , Donantes de Sangre
20.
Front Immunol ; 14: 988947, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37090716

RESUMEN

Introduction: Aspergillus fumigatus (Asp) infections constitute a major cause of morbidity and mortality in patients following allogeneic hematopoietic stem cell transplantation (HSCT). In the context of insufficient host immunity, antifungal drugs show only limited efficacy. Faster and increased T-cell reconstitution correlated with a favorable outcome and a cell-based therapy approach strongly indicated successful clearance of fungal infections. Nevertheless, complex and cost- or time-intensive protocols hampered their implementation into clinical application. Methods: To facilitate the clinical-scale manufacturing process of Aspergillus fumigatus-specific T cells (ATCs) and to enable immediate (within 24 hours) and sustained (12 days later) treatment of patients with invasive aspergillosis (IA), we adapted and combined two complementary good manufacturing practice (GMP)-compliant approaches, i) the direct magnetic enrichment of Interferon-gamma (IFN-γ) secreting ATCs using the small-scale Cytokine Secretion Assay (CSA) and ii) a short-term in vitro T-cell culture expansion (STE), respectively. We further compared stimulation with two standardized and commercially available products: Asp-lysate and a pool of overlapping peptides derived from different Asp-proteins (PepMix). Results: For the fast CSA-based approach we detected IFN-γ+ ATCs after Asp-lysate- as well as PepMix-stimulation but with a significantly higher enrichment efficiency for stimulation with the Asp-lysate when compared to the PepMix. In contrast, the STE approach resulted in comparably high ATC expansion rates by using Asp-lysate or PepMix. Independent of the stimulus, predominantly CD4+ helper T cells with a central-memory phenotype were expanded while CD8+ T cells mainly showed an effector-memory phenotype. ATCs were highly functional and cytotoxic as determined by secretion of granzyme-B and IFN-γ. Discussion: For patients with IA, the immediate adoptive transfer of IFN-γ+ ATCs followed by the administration of short-term in vitro expanded ATCs from the same donor, might be a promising therapeutic option to improve the clinical outcome.


Asunto(s)
Aspergilosis , Linfocitos T CD8-positivos , Aspergillus fumigatus , Aspergilosis/terapia , Linfocitos T Colaboradores-Inductores , Inmunoterapia , Interferón gamma
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