The treatment of thalassemia is still essentially based on continuous transfusion supporting using red cell concentrates (RCC) prepared in different ways. For patients with sickle-cell disorders, ...either urgent or chronic red blood cell transfusion therapy, is widely used in the management of sickle cell disease (SCD) because it reduces HbS level and generally prevents recurrent vaso-occlusive disease (VOD). Recently, the introduction of prestorage filtration to remove leukocytes and the use of techniques for multicomponent donation have increased the types of blood components available for transfusion purposes. The clinical effects of different types of blood components in thalassaemic and sickle-cell patients have not been extensively studied so far. We evaluated the impact of the various different blood components currently available on transfusion needs, transfusion intervals and adverse reactions in order to determine which is the most advantageous for transfusion-dependent thalassaemic and sickle-cell patients followed in our centre. We believe that the optimal characteristics of the RCC are aged less than 10 days from time of collection; Hb content greater than 56
g per unit; Hct: 55–60%; volume (including additive) 300
mL
±
20%; leucodepleted to less than 200,000
leukocytes pert unit; low cytokine content (achievable by prestorage filtration carried out between two and 24
hours after the collection); lack of microaggregates (achievable by prestorage filtration or filtration in the laboratory) and protein content less than 0.5
g per unit for patients allergic to plasma proteins (achievable with manual or automated washing).
It is still recommended that the blood transfused should be as fresh as possible, compatible with the centre's product availability and the centre's organisation should be continuously adapted to this aim. We always transfuse blood within 10 days of its collection, respecting Rh and Kell system phenotypes. Prestorage filtration is strongly recommended, both in order to prevent adverse reactions through the marked leucodepletion (less than 200,000
leukocytes per unit) and for a better standardisation of the final product, including the certainty that the product does not contain clots, an assurance that bed-side filtration cannot give. The RCC should be produced using a method causing as little as possible stress to the red cell membrane. The use of RCC with a high content of Hb (less than 56
g per unit) is strongly recommended, because our study clearly shows that this reduces the number of exposures to donors and the number of accesses to hospital, thus improving the patient's quality of life.
Le traitement de la thalassémie reste essentiellement basé sur la transfusion de concentrés de culots globulaires (CGR) préparés de diverses manières. Dans les désordres drépanocytaires, la transfusion chronique ou en urgence de CGR est largement utilisée dans la gestion de la maladie, car elle permet de réduire le taux de HbS et prévient généralement les accidents vaso-occlusifs récurrents. Récemment, l’introduction de la déleucocytation avant conservation et l’utilisation de techniques multidons ont permis d’augmenter le nombre de composants sanguins transfusionnels disponibles. L’efficacité clinique de ces divers composants sanguins chez les sujets thalassémiques et drépanocytaires n’a pas été examinée jusqu’à présent. Nous avons évalué l’impact des composants actuellement disponibles sur les besoins transfusionnels, l’intervalle entre les transfusions et les réactions secondaires afin de déterminer lequel est le plus avantageux pour les malades transfusion-dépendants de notre centre. Nous pensons que les caractéristiques optimales des CGR sont âge inférieur à dix jours après prélèvement ; contenu Hb supérieur à 56
g par unité ; Htc: 55–60 % ; volume (avec additif): 300
ml
±
20 % ; leucodéplétion: supérieur à 20 000
leucocytes par unité ; faible contenu en chimiokines (réalisable par filtration deux à 24
heures après prélèvement) ; absence de microaggrégats (réalisable par préfiltration ou filtration au laboratoire) ; contenu en protéines inférieur à 0.5
g par unité pour les maladies allergiques aux proteines plasmatiques (réalisable par lavage manuel ou automatique).
On recommande d’utiliser des CGR aussi fraîchement prélevés que possible selon les disponibilités du centre de production et l’organisation des Centres devrait en permanence s’adapter à ce besoin. Nous transfusons toujours du sang prélevé dans les dix jours, en respectant les compatibilités Rh et Kell. La déleucocytation avant stockage est fortement recommandée à la fois pour éviter des réactions secondaires grâce à une diminution drastique du nombre de leucocytes (inférieur à 2 000 000 par CGR) et pour une meilleure standardisation du produit final, incluant la certitude que le produit ne contient pas de caillots, ce que ne peut pas garantir une filtration au lit du malade. Le CGR devrait être préparé à l’aide d’une méthode occasionnant le moins possible de stress à la membrane érythrocytaire. L’utilisation de CGR à contenu élevé en Hb (supérieur à 56
g par unité) est fortement recommandée, car notre étude indique clairement que cela réduit le nombre d’expositions à des donneurs et le nombre de séjours hospitaliers, améliorant ainsi la qualité de vie des malades.
BackgroundAzacitidine belongs to the group of antimetabolites (an analogue of cytidine) used in myelodysplastic syndrome (MS) and in acute myeloid leukaemia (AML), with expected progression free ...survival(according to the characteristics product summary) of 24.6 months for patient with MS and AML with blasts ≤30%.PurposeTo describe the clinical cases of patients affected by MS and AML.Material and methodsWe performed a retrospective study enrolling all patients with MS and AML treated in our hospital. We looked at the medical records and AIFA monitoring folders, and compared effectiveness with progression free survival in the characteristics product summary.Results21 patients were treated with azacitidine: 9 patients were affected by ALM and 12 patients were affected by MS. In the first group, we had 8 responders and 1 non-responder (treatment outcome determined with follow-up at 6 months); in the second group there were 4 non-responders. According to clinical studies with a protocol of azacitidine 1–6 +1, the administration method used was: intramuscularly for 6 days (Monday–Saturday) with a break on Sunday and the last administration on the following Monday, repeated every 28 days. We observed a longer progression free survival in two patients. The patient affected by MS, 68 years old, had white blood cells 1600, haemoglobin 8.4 and platelets 25 000 at the start of treatment. He was classified as intermediate–high risk with blasts 5–10%. The patient was treated with azacitidine for 60 months, with an increase in progression free survival of 35.4 months. The patient dropped out of therapy for progression; he is alive and is doing supportive care.The patient affected by ALM, 76 years old, had white blood cells 30 400, haemoglobin 7.9 and platelets 41 000 at the start of treatment. Blasts were >20%. The patient was treated with azacitidine for 59 months, with an increase in progression free survival of 34.4 months. He is still being treated with azacitidine.ConclusionWe have shown a high efficacy for azacitidine in increasing the progression free survival in most patients treated, with two over level clinical cases (10% of the patients studied).No conflict of interest
BackgroundIn relation to the regional project UFAONCOEMA, at the enterprise level, a set of goals were fixed. They concerned: efficacy, efficiency, quality and performance safety. Among the quality ...goals, monitoring of waiting time for antiblastic chemotherapies was chosen as an indicator.PurposeThe purpose was to assess, for two UFA (antiblastic drugs unit) which joined the UFAONCOEMA project, whether waiting times met the requirements of a maximum of 60 min, set at the enterprise level, according to the standard requirements adopted by other reference enterprises.Material and methodsTimes were monitored over a period of 3 months. Monitoring started from therapy’s online confirmation by the prescriber, to pharmacist validation, to preparation and delivery by nurses, and ended when the unit received that therapy. Therapies for 2018 patients in the oncology and haematology day hospital (DH) were evaluated. It has been considered that after verifying the appropriateness of the prescription, validation starts at about 8.15am, and preparation in a clean room starts at about 8.45am, due to set up of the laminar flow hood and sterile field.ResultsFrom when it is possible to make the preparation to the moment of delivery to the unit, under optimal conditions (3 nurses present, no extraordinary maintenance for the hood and/or UFA machinery), for therapies confirmed the same morning when the administration is expected, waiting times are 60 min for oncology and 57 min for haematology. Considering that therapies for the afternoon shift in the oncology DH and therapies confirmed on time for the following day are made and sent before 1.30pm, waiting time for those patients (10% of therapies) is zero, so the average waiting time reduces to 56 min.ConclusionThis assessment shows that the average waiting times are included in a range of fixed requirements. 32% of morning therapies reach the applicant units within 50 mins. Transportation time (10 min) to the oncology DH, even it does not negatively affect the achievement of the goal, can be reduced with future transfer of the UFA centre in that unit. An increase in confirmed steady therapies for the day after can further reduce waiting time.No conflict of interest.
Background:
Up to 50% of hairy cell leukemia (HCL) patients relapse after purine analogs. We identified the BRAF‐V600E kinase mutation as the genetic cause of HCL (Tiacci et al., NEJM 2011). We then ...documented, in 26 relapsed/refractory patients treated with the oral BRAF inhibitor vemurafenib for a median of 16 weeks, 96% of overall responses (including 35% complete remissions ‐ CR), obtained after a median of 8 weeks (Tiacci et al., NEJM 2015). However, residual bone marrow (BM) HCL cells persisted even in CR patients (5–10% cells) and the median relapse‐free survival among all responding patients was 9 months.
Aims:
Since HCL strongly expresses CD20, rituximab could improve the efficacy of BRAF inhibition by targeting leukemic cells resistant to vemurafenib.
Methods:
In this academic, phase‐2, single‐arm, single‐center trial (EudraCT 2014‐003046‐27), relapsed/refractory HCL patients received vemurafenib (960 mg b.i.d.) for 8 weeks and concomitant rituximab (375 mg/m2 i.v.) every 2 weeks. Rituximab was then given as consolidation 4 times every 2 weeks after the end of vemurafenib. CR required normal blood counts, no palpable splenomegaly, and no leukemic cells at morphologic analysis of BM biopsies and blood smears.
Results:
We enrolled 31 patients (median age: 59 years) with a median of 3 previous therapies, including 8 primary refractory cases (26%). Toxicity was mostly of grade 1‐2, without myelosuppression, and overlapped that of either drug when used alone.
Strikingly, a CR was achieved by 26/27 (96%) patients evaluable for efficacy, including 2 patients with incomplete platelet recovery at the end of treatment who however normalized the platelet count soon after; and 2 patients with incomplete resolution of splenomegaly who nonetheless remain in otherwise continuous CR at 22.5 and 25 months from the end of treatment. Among the 26 CR cases, all previously treated with purine analogs, there were also some patients previously refractory to rituximab (n = 5) and/or who had relapsed after a prior BRAF inhibitor (n = 7; 5 obtained a short‐lived PR and 2 a CR after treatment with the BRAF inhibitor). Notably, a CR was obtained after just 4 weeks of vemurafenib and two concomitant doses of rituximab in 15/24 evaluable patients (63%). Minimal residual disease (MRD) by allele‐specific PCR (sensitivity: 0.05% BRAF‐V600E alleles) was absent in the BM of 17/26 (65%) patients; in 8/17 patients (47%), MRD clearing was obtained before rituximab consolidation.
Progression‐free survival (PFS) in the 29 evaluable patients was 83% at a median follow‐up of 29.5 months (range: 2–45) (Fig. 1A). Progressions (n = 5) always occurred in cases who were MRD‐positive, including 3/5 patients whose immediate prior treatment was a BRAF inhibitor (leading to PR in all 3 cases). Indeed, PFS was significantly longer in MRD‐negative CR cases (100% in 17 patients at 30.5 months of median follow‐up) than in MRD‐positive CR cases (44% in 9 patients at a median follow‐up of 24.5 months) (p = 0.001; Fig. 1B). In subsequent BM evaluations, 16/17 (94%) CR patients maintained a MRD‐negative status after a median of 22.5 months (range 12.5–36.5); in the remaining patient, MRD reappeared 12.5 months later but he remains in continuous CR at 38 months after the end of treatment.
Summary/Conclusion:
Vemurafenib plus rituximab is a brief, safe and non‐myelotoxic regimen that induces MRD‐negative durable responses in the majority of relapsed/refractory HCL patients. Randomized testing of this regimen against the chemotherapy‐based standard of care in the frontline setting is warranted.
•Innovative system able to measure instantaneous evapotranspiration during irrigation.•An evapotranspiration decrease has been observed within irrigation periods.•System will allow to determine ...evapotranspiration in different irrigation conditions.•Filtering techniques are essential to obtain instantaneous evapotranspiration.
In years, the availability of water for irrigation is one of the main problems in Mediterranean Agriculture. That is why new technologies must be used to achieve proper irrigation management which is the main determinant of the quality and quantity of harvests and involves determining crop water needs. This paper presents a study for the development and implementation of an instrumentation system capable of accurately determining water balance during irrigation periods using a weighing lysimeter for potted crops. The mechanical structure of the lysimeter was designed and validated by our research group in previous works. In the design, the main requirements were high precision and low cost to make it affordable to most farmers. For this reason, the system was implemented using an open source platform and precision instrumentation to ensure accuracy of the measurements. A high-precision flowmeter was used to monitor the supplied irrigation water. The system was also capable of sending data wirelessly to a server in the cloud so they could be later queried from any device with Internet access. Field trials were conducted in order to collect data in both irrigation and non-irrigation periods. The application of filtering techniques was required, so a Savitzky-Golay smoothing algorithm was selected to obtain reliable data of instantaneous evapotranspiration. In the data analyzed, a decrease between 10% and 20% was observed in the hourly evapotranspiration during the irrigation intervals.
We tracked the results of 394 manual or automatic red blood cell exchanges done with a cell separator in 20 sickle cell patients at high risk for recurrent complications. Over an average of 6 years, ...none of the patients developed complications related to the procedure or to the increased blood use. It was safe and effective in preventing complications of sickle cell disease, and if done automatically, reduced iron overload. Ferritin levels also decreased in patients treated with automatic red blood cell exchange. Furthermore, using Single Donor Red Blood Cell units (SDRC) we reduced the potential exposure to transfusion transmitted infectious diseases (TTI).
Hairy-cell leukemia (HCL) is a CD20+ indolent B-cell cancer in which a BRAF V600E kinase-activating mutation plays a pathogenetic role. In clinical trials involving patients with refractory or ...relapsed HCL, the targeting of BRAF V600E with the oral BRAF inhibitor vemurafenib led to a response in 91% of the patients; 35% of the patients had a complete response. However, the median relapse-free survival was only 9 months after treatment was stopped.
In a phase 2, single-center, academic trial involving patients with refractory or relapsed HCL, we assessed the safety and efficacy of vemurafenib (960 mg, administered twice daily for 8 weeks) plus concurrent and sequential rituximab (375 mg per square meter of body-surface area, administered for 8 doses over a period of 18 weeks). The primary end point was a complete response at the end of planned treatment.
Among the 30 enrolled patients with HCL, the median number of previous therapies was 3. A complete response was observed in 26 patients (87%) in the intention-to-treat population. All the patients who had HCL that had been refractory to chemotherapy (10 patients) or rituximab (5) and all those who had previously been treated with BRAF inhibitors (7) had a complete response. Thrombocytopenia resolved after a median of 2 weeks, and neutropenia after a median of 4 weeks. Of the 26 patients with a complete response, 17 (65%) were cleared of minimal residual disease (MRD). Progression-free survival among all 30 patients was 78% at a median follow-up of 37 months; relapse-free survival among the 26 patients with a response was 85% at a median follow-up of 34 months. In post hoc analyses, MRD negativity and no previous BRAF inhibitor treatment correlated with longer relapse-free survival. Toxic effects, mostly of grade 1 or 2, were those that had previously been noted for these agents.
In this small study, a short, chemotherapy-free, nonmyelotoxic regimen of vemurafenib plus rituximab was associated with a durable complete response in most patients with refractory or relapsed HCL. (Funded by the European Research Council and others; HCL-PG03 EudraCT number, 2014-003046-27.).
This paper describes a comparative experimental and analytical study of the maximum bending load in timber beams of Pinus sylvestris L. having natural defects (knots, grain deviations, fissures and ...wanes) that are reinforced with carbon fiber composite (CFRP). Beams extracted during rehabilitation of the roof frame of the School of Law, University of Granada, had been in service for over two hundred years. Two commercial CFRP pultruded laminates were applied as reinforcement, for comparison. Both were properly glued with epoxy resin on the tension side of the beams, partially covering the area on this side. It is clearly shown that, due to the abundance of defects, using the elastoplastic constitutive law of timber and assuming the same tension and compression elastic moduli in the cross-section equilibrium method, the analytical values for the bending load capacity will not match the experimental ones. However, this assumption has been traditionally used in most previous research on timber beams reinforced with composite materials. As an alternative, a more general model for the timber may be used, in which the two moduli are considered to be different in compression and tension stresses. Results demonstrate how this modification provides a much better match between analytical and experimental values of the bending load capacity. The improvement is especially evident for beams with natural defects and many years in service, reinforced with CFRP for rehabilitation purposes. Moreover, a better mechanical behavior of the reinforced specimens is obtained, when compared with the control ones (without reinforcement): reinforcement induced an improvement of up to 88% in bending load capacity.
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