Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients.

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution. TRIAL REGISTRATION: Clinicaltrials.gov NCT04621123 and NCT04589949. REGISTRATION: NCT04621123 and NCT04589949 on https://www. CLINICALTRIALS: gov.

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial.

BACKGROUND: Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123. FINDINGS: Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log10 copies per mL (1·43) with placebo (crude difference -0·10 log10 copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention. INTERPRETATION: Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded. FUNDING: Grifols, Crowdfunding campaign YoMeCorono.

Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective.

Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime. Approximately 75% of these patients will also require immunosuppressive drugs (i.e., thiopurines or biological agents) in the mid-term to avoid colectomy. Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and co-morbid patients, underlining the unmet need for safer alternative therapies. Granulocyte/monocytapheresis (GMA), a CE-marked, non-pharmacological procedure for the treatment of ulcerative colitis (among other immune-mediated diseases), remains the only therapy targeting neutrophils, the hallmark of pathology in ulcerative colitis. GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile. In spite of being a first line therapy in Japan, GMA use is still limited to a small number of centres and countries in Europe. In this article, we aim to give an overview from a European perspective of the mechanism of action, recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.

SARS-CoV-2/COVID-19 pandemic: first wave, impact, response and lessons learnt in a fully integrated Regional Blood and Tissue Bank. A narrative report.

BACKGROUND: The COVID-19 pandemic is placing blood and tissue establishments under unprecedented stress, putting its capacity to provide the adequate care needed at risk. Here we reflect on how our integrated organisational model has faced the first impact of the pandemic and describe what challenges, opportunities and lessons have emerged. MATERIALS AND METHODS: The organisational model of the Catalan Blood and Tissue Bank (Banc de Sang i Teixits, BST) is described. The new scenario was managed by following international recommendations and considering the pandemic in a context of volatility, uncertainty, complexity, and ambiguity (VUCA), allowing rapid measures to be taken. These aimed to: ensure donor safety, promote proper responses to patients' needs, ensure the health and well-being of personnel, and prepare for future scenarios. RESULTS: The BST has adapted its activities to the changes in demand. No shortage of any product or service occurred. Donor acceptance, safety and wellbeing were maintained except for tissue donation, which almost completely stopped. To support the health system, several activities have been promoted: large-scale convalescent plasma (CP) production, clinical trials with CP and mesenchymal stromal cells, massive COVID-19 diagnoses, and participation in co-operative research and publications. Haemovigilance is running smoothly and no adverse effects have been detected among donors or patients. DISCUSSION: Several elements have proven to be critical when addressing the pandemic scenario: a) the early creation of a crisis committee in combination with technical recommendations and the recognition of a VUCA scenario; b) identification of the strategies described; c) the integrated donor-to-patient organisational model; d) active Research and Development (R&D); and e) the flexibility of the staff. It is essential to underline the importance of the need for centralised management, effective contingency strategies, and early collaboration with peers.

Diagnostic performance of the ClearLLab 10C B cell tube.

INTRODUCTION: Pre-analytical and analytical errors can threaten the reliability of flow cytometry (FC) results. A potential solution to some of these is the use of dry, pre-mixed antibodies, such as the ClearLLab 10C system. The purpose of the present study was to compare the diagnostic performance of the ClearLLab 10C B cell tube with that of our standard laboratory practice. METHODS: We compared the diagnoses made with the ClearLLab 10C B cell tube (experimental strategy) with those made with standard laboratory practice (standard strategy). Samples were selected aiming for representation of the full spectrum of B cell disorders, with an emphasis on mature B cell malignancies, as well as healthy controls. RESULTS: We included 116 samples (34 normal controls, 4 acute lymphoblastic leukemias, 54 mature lymphoproliferative disorders in peripheral blood and bone marrow, 3 myelomas, 6 bone marrow samples with involvement by lymphoma and 1 with elevated hematogone count, 14 lymph node samples, 1 cerebrospinal fluid, and 1 pleural effusion). There were two diagnostic errors (1.7%). The agreement between the two strategies in the percentage of CD19 cells and fluorescence intensity of CD5, CD19, CD20, CD200, and CD10 was very good. CONCLUSIONS: In this study, the ClearLLab 10C B cell tube performed similarly to our standard laboratory practice to diagnose and classify mature B cell malignancies.

Efficacy and Safety of Plasma Exchange with 5% Albumin to Modify Cerebrospinal Fluid and Plasma Amyloid-ß Concentrations and Cognition Outcomes in Alzheimer's Disease Patients: A Multicenter, Randomized, Controlled Clinical Trial.

BACKGROUND: Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-ß (Aß) peptide between cerebrospinal fluid (CSF) and plasma compartments. OBJECTIVE: To determine whether plasma exchange (PE) with albumin replacement was able to modify Aß concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD). METHODS: In a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein®, Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF Aß1-40 and Aß1-42 levels, as well as cognitive, functional, and behavioral measures were determined. RESULTS: CSF Aß1-42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5 pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma Aß1-42 levels were lower in the PE-treated group after each treatment period (p < 0.05). Plasma Aß1-40 levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and Semantic Verbal Fluency (p < 0.05) throughout the study. Neuropsychiatric Inventory scores were higher in controls during the PE phase (p < 0.05). CONCLUSION: PE with human albumin modified CSF and plasma Aß1-42 levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued.

Anemia hemolítica autoinmunitaria refractaria a tratamiento médico tras ingesta de dióxido de clorina en un paciente con púrpura trombocitopénica inmunitaria / Autoimmune hemolytic anemia refractory to medical treatment after chlorine dioxide intake in a patient with idiopathic thrombocytopenic purpura

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Mobilization and engraftment of peripheral blood stem cells in healthy related donors >55 years old.

BACKGROUND AIMS: The increasing scarcity of young related donors has led to the use of older donors for related allogeneic hematopoietic stem cell transplantation (HSCT). This study analyzed the influence of age on the results of mobilization of peripheral blood stem cells (PBSCs) in healthy donors as well as on the engraftment and outcome of HSCT. METHODS: A retrospective analysis from a single center was performed comparing the results of PBSC mobilization from related healthy donors according to their age. RESULTS: The study included 133 consecutive related donors. The median age was 50 years (range, 4-77 years); 70 (53%) donors were males, and 44 (33%) were >55 years old. All donors were mobilized with granulocyte colony-stimulating factor for 5 days. The peak CD34(+) cell count in peripheral blood was higher in younger than in older donors (median, 90.5 CD34(+) cells/µL [range, 18-240 CD34(+) cells/µL] versus 72 CD34(+) cells/µL [range, 20-172.5 CD34(+) cells/µL], P = 0.008). The volume processed was lower in younger than in older donors (16,131 mL [range, 4424-36,906 mL] versus 18,653 mL [range, 10,003-26,261 mL], P = 0.002) with similar CD34(+) cells collected (579.3 × 10(6) cells [range, 135.14 × 10(6)-1557.24 × 10(6) cells] versus 513.69 × 10(6) cells [range, 149.81 × 10(6)-1290 × 10(6) cells], P = 0.844). There were no differences in time to recovery of neutrophils and platelets or in the incidences of acute and chronic graft-versus-host disease, overall survival, non-relapse mortality and relapse incidence. CONCLUSIONS: Donors >55 years old mobilized fewer CD34(+) cells and required a greater volume to collect a similar number of CD34(+) cells. The outcome of HSCT was not influenced by donor age. Donor age should not be a limitation for related allogeneic HSCT.

Reconstruccion de la mama con gel de plaquetas en la cirugia conservadora del cancer / Use of platelet gel in breast reconstruction after breast-conserving cancer surgery

Introducción: Con la finalidad de disminuir las deformidades de la mama después de la cirugía conservadora del cáncer, presentamos una nueva técnica de reconstrucción mamaria mediante la restitución del volumen mamario con gel de plaquetas. Pacientes y métodos Estudio piloto de 20 pacientes con cáncer de mama sometidas a tumorectomía a las que se aplicó en el espacio residual el gel obtenido por plaquetoaféresis de donante alogénico sano. A las pacientes se les realizó un seguimiento clínico, iconográfico e histológico, así como una valoración del resultado estético. Resultados La edad media fue de 50,5±8,65 años (rango 42-70 años) y la mediana del índice de comorbilidad de Charlson fue de 1,15±1,27 (rango 0-5). El volumen medio de la tumorectomía fue de 63,1±31,1ml (rango 30-160ml) y el volumen de restitución con el gel de plaquetas fue de 111,5±60,9ml (rango 40-250ml). Después de una mediana de seguimiento de medio de 17 meses, el 80% de las pacientes preservaron el volumen mamario y no fueron necesarias reintervenciones por afectación de los márgenes quirúrgicos ni se observaron recidivas. Conclusiones El gel de plaquetas permite restituir el volumen mamario ajustado al volumen de la tumorectomía, minimizando las retracciones y deformidades habituales de la cirugía conservadora, lo que permite realizar resecciones amplias con márgenes oncológicos de seguridad (AU)

Introduction: With the aim of decreasing breast defects after conservative cancer surgery, we present a new breast reconstruction technique using breast volume restitution with platelet gel. Patients and method: A pilot study was conducted on 20 breast cancer patients undergoing tumorectomy with placement a gel obtained by platelet pheresis of a healthy allogeneic donor in the surgical cavity. Patients had a clinical, photographic and histological follow-up, as well as an assessment of the aesthetic outcome. Results: The mean age was 50.5 8.6 years (range 42-70 years) and with a mean Charlson comorbidity index of 1.1 1.2 (range 0-5). The mean tumour volume was 63.1 31.1 ml(range 30-160 ml) and the mean restitution volume with platelet gel was 111.5 60.9 ml (range40-250 ml). After a mean follow-up of 17 months, 80% of the patients maintained the breast volume and no further operations were needed due to surgical margin involvement. No recurrences were observed in any patient. Conclusions: Platelet gel allows restitution of the breast volume adjusted to the tumorectomy volume, minimising the usual retractions and deformities after conservative surgery. It enables wide resections and safety margins (AU)

[Use of platelet gel in breast reconstruction after breast-conserving cancer surgery]. / Reconstrucción de la mama con gel de plaquetas en la cirugía conservadora del cáncer.

INTRODUCTION: With the aim of decreasing breast defects after conservative cancer surgery, we present a new breast reconstruction technique using breast volume restitution with platelet gel. PATIENTS AND METHOD: A pilot study was conducted on 20 breast cancer patients undergoing tumorectomy with placement a gel obtained by plateletpheresis of a healthy allogeneic donor in the surgical cavity. Patients had a clinical, photographic and histological follow-up, as well as an assessment of the aesthetic outcome. RESULTS: The mean age was 50.5±8.6 years (range 42-70 years) and with a mean Charlson comorbidity index of 1.1±1.2 (range 0-5). The mean tumour volume was 63.1±31.1 ml (range 30-160 ml) and the mean restitution volume with platelet gel was 111.5±60.9 ml (range 40-250 ml). After a mean follow-up of 17 months, 80% of the patients maintained the breast volume and no further operations were needed due to surgical margin involvement. No recurrences were observed in any patient. CONCLUSIONS: Platelet gel allows restitution of the breast volume adjusted to the tumorectomy volume, minimising the usual retractions and deformities after conservative surgery. It enables wide resections and safety margins.

Predictive factors for poor peripheral blood stem cell mobilization and peak CD34(+) cell count to guide pre-emptive or immediate rescue mobilization.

BACKGROUND AIMS: Failure in mobilization of peripheral blood (PB) stem cells is a frequent reason for not performing hematopoietic stem cell transplantation (HSCT). Early identification of poor mobilizers could avoid repeated attempts at mobilization, with the administration of pre-emptive rescue mobilization. METHODS: Data from the first mobilization schedule of 397 patients referred consecutively for autologous HSCT between 2000 and 2010 were collected. Poor mobilization was defined as the collection of < 2 × 10(6) CD34(+)cells/kg body weight (BW). RESULTS: The median age was 53 years (range 4-70) and 228 (57%) were males. Diagnoses were multiple myeloma in 133 cases, non-Hodgkin's lymphoma in 114, acute myeloid leukemia or myelodysplastic syndrome in 81, Hodgkin's lymphoma in 42, solid tumors in 17 and acute lymphoblastic leukemia in 10. The mobilization regimen consisted of recombinant human granulocyte-colony-stimulating factor (G-CSF) in 346 patients (87%) and chemotherapy followed by G-CSF (C + G-CSF) in 51 (13%). Poor mobilization occurred in 105 patients (29%), without differences according to mobilization schedule. Diagnosis, previous therapy with purine analogs and three or more previous chemotherapy lines were predictive factors for poor mobilization. A CD34(+)cell count in PB > 13.8/µL was enough to ensure ≥ 2 × 10(6) CD34(+)cells/kg, with high sensitivity (90%) and specificity (91%). CONCLUSIONS: The prevalence of poor mobilization was high, being associated with disease type, therapy with purine analogs and multiple chemotherapy regimens. The threshold of CD34(+) cell count in PB identified poor mobilizers, in whom the administration of immediate or pre-emptive plerixafor could be useful to avoid a second mobilization.

Plerixafor plus G-CSF in combination with chemotherapy for stem cell mobilization in a pediatric patient with Ewing's sarcoma.

Some malignant tumors in childhood require high-dose chemotherapy with stem cell support to achieve a cure. In patients heavily pretreated with myelosuppressive chemotherapy or irradiation, granulocyte colony-stimulating factor (G-CSF) may fail to mobilize stem cells from the bone marrow. Based on the experience with lymphoma and myeloma patients in whom peripheral blood-derived stem cell (PBSC) collection following mobilization with G-CSF failed, we successfully employed plerixafor in a 14-year-old female diagnosed with Ewing's sarcoma in early relapse treated with three lines of chemotherapy in whom PBSC could not be mobilized using either G-CSF alone or G-CSF following chemotherapy. No side effects were observed. Plerixafor may be an effective and safe agent for stem cell collection in pediatric patients with solid tumors, although new studies addressed to evaluate its effectiveness and safety are needed.

Respuesta a rituximab en 2 pacientes con púrpura trombótica trombocitopénica refractaria a recambio plasmático / Response to rituximab in two patients with plasma exchange-refractory thrombotic thrombocytopenic purpura

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Enfermedad por crioaglutininas y neumonía neumocócica / Cold agglutin in disease and pneumococal pneumonia

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Vital transfusion in patients with multiple antibodies against common erythrocyte antigens.

The transfusion of blood components could be needed in certain types of surgical procedures. Blood type components and the requested number of units will depend on the estimated loss of blood, type of surgery, surgical technique to be employed and risk factors for bleeding. Problems can appear when multiple antibodies against common erythrocyte antigens are detected in blood samples and this situation worsens if blood units are requested as quickly as possible. We report a case of a patient with a non frequent erythrocytic phenotype where multiple antibodies acting against high-frequency antigens were detected and who required urgent surgery.

[High-dose ifosfamide and etoposide regimen as salvage and mobilization therapy for patients with lymphoma]. / Tratamiento de rescate y movilización de progenitores hematopoyéticos de sangre periférica con altas dosis de ifosfamida y etopósido en pacientes con linfoma.

BACKGROUND AND OBJECTIVE: Several groups have used salvage chemotherapy in relapsed or refractory lymphomas to mobilize peripheral blood stem cells. The objective of this study was to evaluate the antilymphomatous efficacy, the ability of mobilization and the toxicity of a regimen containing high-dose ifosfamide, etoposide, methylprednisolone (IFOVM) and granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHOD: Twenty-four patients with relapsed or refractory lymphoma received IFOVM and G-CSF. The median age was 45 years and 13 were males. The histologyc subtypes of lymphoma were: diffuse large B cell (DLBCL) (n = 15), Hodgkin (n = 2), Burkitt (n = 2), mantle cell (n = 2), anaplastic (n = 1), peripheral T-cell (n = 1) and follicular (n = 1). RESULTS: Two patients died of sepsis within the pancytopenia period. In 17 (77%) of the remaining patients more than 1.5 x 10(6) CD34+ cells/kg (median: 7.7 x 10(6) CD34+ cells/kg) were collected. The median time to peripheral blood stem cells harvest was 17 (range: 13-24) days and 4 patients required 2 procedures of apheresis. Sixteen patients (67%) developed neutropenic fever. The median time to achieve granulocyte cell count > 1 x 10(9)/l and platelet count > 20 x 10(9)/l was 15 and 16 days, respectively. The only factor predicting successful mobilization was the diagnosis of DLBCL (p = 0.04). Ten patients underwent peripheral blood stem cells transplantation. CONCLUSIONS: The regimen IFOVM and G-CSF allows an effective peripheral blood stem cells mobilization in patients with lymphoma, particularly in those with DLBCL, but it is associated with significant toxicity.