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We report our experience with venetoclax/hypomethylating agents (Ven/HMA) in 8 AML patients not candidates for intensive CT or refractory/relapsed with limited treatment options. The response rate was 50%. Venetoclax was well‐tolerated in 62.5% of the patients. Ven/HMA provides a benefit particularly when used in patients without prior HMA exposure. According to our real‐word data, Ven/HMA combination provided benefit to AML patients without prior exposure to HMA, who received it as first‐line treatment for AML with an acceptable safety profile.

Asthma is a prevalent chronic respiratory condition. Most patients can manage their symptoms with standard treatments but approximately 5–10% experience severe uncontrolled asthma (SUA), characterized by persistent symptoms and frequent exacerbations despite optimized therapy. This retrospective, observational, multicentre study conducted in southern Spain aimed to evaluate the effectiveness of benralizumab in patients with SUA and identify predictive markers of response. A total of 99 patients were selected. Mean age of participants was 63 ± 15.3 years. Results showed that 79.8% of patients achieved a 50% reduction in oral corticosteroid (OCS) use, 81.8% experienced at least a 50% reduction in exacerbations, and 75.7% had a ≥ 10% improvement or maintained %forced expiratory volume in 1 s (FEV 1 ) above 80%. Significant improvements were observed in lung function, asthma control, and a reduction in eosinophil levels ( p  < 0.001). The frequency of exacerbations and OCS cycles significantly decreased ( p  < 0.001), and ACT scores improved. The presence of concomitant COPD was associated with a lower probability of lung function improvement, highlighting the importance of phenotypic characterization in treatment response. Importantly, higher baseline eosinophil counts were associated with better clinical outcomes, suggesting their potential as predictive biomarkers. This study supports the real-world effectiveness of benralizumab in reducing OCS dependency, exacerbations, and enhancing pulmonary function in patients with severe uncontrolled asthma.

Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual genetic profiles for heightened efficacy. The era of personalized treatment in CLL signifies a transformative shift, holding the potential for improved outcomes in the conquest of this intricate hematologic disorder. This review plays a role in elucidating the evolving CLL treatment landscape, encompassing all reported genetic factors. Through a comprehensive historical analysis, it provides insights into the evolution of CLL management. Beyond its retrospective nature, this review could be a valuable resource for clinicians, researchers, and stakeholders, offering a window into the latest advancements. In essence, it serves as a dynamic exploration of our current position and the promising prospects on the horizon.

The therapeutic approach to chronic myeloid leukaemia (CML) has changed in recent years. As a result, a high percentage of current patients in the chronic phase of the disease almost have an average life expectancy. Treatment also aims to achieve a stable deep molecular response (DMR) that might allow dose reduction or even treatment discontinuation. These strategies are often used in authentic practices to reduce adverse events, yet their impact on treatment-free remission (TFR) is a controversial debate. In some studies, it has been observed that as many as half of patients can achieve TFR after the discontinuation of TKI treatment. If TFR was more widespread and globally achievable, the perspective on toxicity could be changed. We retrospectively analysed 80 CML patients treated with tyrosine kinase inhibitor (TKI) at a tertiary hospital between 2002 and 2022. From them, 71 patients were treated with low doses of TKI, and 25 were eventually discontinued, 9 of them being discontinued without a previous dose reduction. Regarding patients treated with low doses, only 11 of them had molecular recurrence (15.4%), and the average molecular recurrence free survival (MRFS) was 24.6 months. The MRFS outcome was not affected by any of the variables examined, including gender, Sokal risk scores, prior treatment with interferon or hydroxycarbamide, age at the time of CML diagnosis, the initiation of low-dose therapy and the mean duration of TKI therapy. After TKI discontinuation, all but four patients maintained MMR, with a median follow-up of 29.2 months. In our study, TFR was estimated at 38.9 months (95% CI 4.1–73.9). This study indicates that low-dose treatment and/or TKI discontinuation is a salient, safe alternative to be considered for patients who may suffer adverse events (AEs), which hinder the adherence of TKI and/or deteriorate their life quality. Together with the published literature, it shows that it appears safe to administer reduced doses to patients with CML in the chronic phase. The discontinuation of TKI therapy once a DMR has been reached is one of the goals for these patients. The patient should be assessed globally, and the most appropriate strategy for management should be considered. Future studies are needed to ensure that this approach is included in clinical practice because of the benefits for certain patients and the increased efficiency for the healthcare system.

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3–6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin’s lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.

The effectiveness of venetoclax (VEN) in relapsed or refractory acute myeloid leukemia (RR-AML) has not been well established. This retrospective, multicenter, observational database studied the effectiveness of VEN in a cohort of 51 RR-AML patients and evaluated for predictors of response and overall survival (OS). The median age was 68 years, most were at high risk, 61% received ≥2 therapies for AML, 49% had received hypomethylating agents, and ECOG was ≥2 in 52%. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi), was 12.4%. Additionally, 10.4% experienced partial response (PR). The CR/CRi was higher in combination with azacitidine (AZA; 17.9%) than with decitabine (DEC; 6.7%) and low-dose cytarabine (LDAC; 0%). Mutated NPM1 was associated with increased CR/CRi. Median OS was 104 days (95% CI: 56–151). For the combination with AZA, DEC, and LDAC, median OS was 120 days, 104 days, and 69 days, respectively; p = 0.875. Treatment response and ECOG 0 influenced OS in a multivariate model. A total of 28% of patients required interruption of VEN because of toxicity. Our real-life series describes a marginal probability of CR/CRi and poor OS after VEN-based salvage. Patients included had very poor-risk features and were heavily pretreated. The small percentage of responders did not reach the median OS.

Most malignant hematological diseases are generally a consequence of acquired mutations or rearrangements in cell replication processes. Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease that results from acquired genetic and epigenetic alterations in hematopoietic progenitor cells. Despite the advances made in understanding the pathogenesis of this disease, the overall survival of patients remains very low due to the high relapse rate. Pharmacogenetics and massive sequencing studies have allowed the identification of new recurrent mutations with significant prognostic impact in AML; furthermore, it seems likely that whole genome sequencing will soon become a standard diagnostic test, which will allow the molecular diagnosis of patients. Therefore, it is necessary to develop molecular targets that open new therapeutic perspectives and allow individualized treatment of patients with this aggressive disease. Chronic myeloid leukemia (CML) is the first neoplastic disease for which a characteristic genetic alteration was described. It has, by definition, a genetic marker, the BCR::ABL1 rearrangement, as a consequence of the t9;22(q34;q11) translocation. Its study is essential for the diagnosis of this entity and also for monitoring the response to treatment. Drugs known as tyrosine kinase inhibitors (TKIs) that target the BCR::ABL1 protein (oral targeted therapy) are the conventional treatment of CML, representing a change of paradigm in the management of oncohematological patients.

The hypomethylating agents, decitabine (DEC) and azacitidine (AZA), allowed more elderly acute myeloid leukemia (AML) patients to be treated. However, there are little direct comparative data on AZA and DEC. This multicenter retrospective study compared the outcomes of AZA and DEC in terms of response and overall survival (OS). Potential predictors associated with response and OS were also evaluated. A total of 626 AML patients were included (487 treated with AZA and 139 with DEC). Response rates were similar in both groups: CR was 18% with AZA vs. 23% with DEC (p = 0.20), CR/CRi was 20.5% vs. 25% (p = 0.27) and ORR was 32% vs. 39.5% (p = 0.12), respectively. Patients with leukocytes < 10 × 109/L, bone marrow blasts < 50% and ECOG ≥ 2 had higher ORR with DEC than with AZA. OS was similar in both groups: 10.4 months (95% CI: 9.2–11.7) vs. 8.8 months (95% CI: 6.7–11.0, p = 0.455), for AZA and DEC, respectively. Age (≥80 years), leukocytes (≥ 10 × 109/L), platelet count (<20 × 109/L) and eGFR (≥45 mL/min/1.73 m2) were associated with higher OS with AZA compared to DEC. In conclusion, we found no differences in response and OS rates in AML patients treated with AZA or DEC.

Tungsten (W) and its alloys are being considered as a major candidate for the plasma-facing components (PFCs) in future fusion devices. Being versatile and able to perform in situ measurements, laser-induced breakdown spectroscopy (LIBS) is the most promising analytical tool for the elemental characterization of fusion-relevant materials. The present article studies the use of calibration free (CF)-LIBS for the characterization of the plasma generated from tantalum (Ta) and elemental quantification of WTa (5 at.%) + Deuterium (D) (10 at.%) sample (coating thickness ~ 3 µm) on molybdenum (Mo) substrate, using a high energy Nd:YAG laser (1064 nm, pulse duration 8 ns). The laser energy has been optimized (58 mJ/pulse) for given samples, and the laser-induced plasma was generated on the surface by means of focussing the laser. All the experimental measurements have been performed in air at atmospheric pressure and room temperature. For the quantification of WTa + D coating, measurements have also been performed under the flow of nitrogen gas. For the detection of the analytes, both gate delay ( t d ) and gate width ( t g ) were optimized. For the CF quantification, it has been found that the most appropriate gate times were t d  =  t g  = 1 µs, considering thermodynamic equilibrium. Suitable emission from both neutral and ionic species has been considered for the evaluation of the plasma temperature and electron density using the Boltzmann and Saha–Boltzmann plots approaches, respectively. This work provides a step towards CF-LIBS quantification and depth profile analysis studies for WTa-based materials and D retention in it. These results have been compared with those obtained by other analytical techniques (TOF-ERDA and GDOES).

Background Although SARS-Cov-2 outcomes have improved in the Omicron era, the synergistic or additive effects between SARS-CoV-2 Omicron variants and other microbiological agents in adult hematologic patients have been little explored. We aimed to characterize co-infection types, identify risk factors for co-infection and determine co-infection-related mortality in hematologic patients and recipients of cellular therapy with a first episode of SARS-CoV-2 infection in the Omicron era. Methods Retrospective national Spanish registry analysis of 692 consecutive patients with hematological disease including receptors of cellular therapy from December 2021 to May 2023. Results The co-infection rate was 9% ( n  = 64), 30% of which were polymicrobial. Bacterial, viral, and fungal agents affected 64%, 30%, and 11% of patients, respectively. Among the microbiologically confirmed agents ( n  = 82), the most common sites of identification were lower respiratory tract (33%), urinary tract (27%) and bloodstream (17%). Multivariable analysis identified cardiopathy (hazard ratio [HR] 1.69), CAR-T therapy (HR 3.42) and pneumonia (HR 5.54) as conditions associated with co-infection. Considering all-cause mortality at day 180 after SARS-CoV-2 detection, co-infection was associated with lower survival (71% versus 92%). Risk factors at COVID-19 diagnosis for non-relapse mortality (NRM) were co-infection (HR 4.28), age ≥ 64 years old (HR 2.55), active hematological treatment (HR 2.13) and under corticosteroid treatment (HR 3.21). In co-infected patients, the only identified factor increasing NRM was corticosteroid use (HR 3.33) at the time of SARS-CoV-2 detection. Conclusions SARS-CoV-2 co-infection are relatively frequent in hematologic patients and cellular therapy recipients in the Omicron era. Patients with ischemic cardiopathy, those presenting with pneumonia and recipients of CAR-T are at a higher risk of developing a co-infection, while co-infection, age ≥ 64 years old, active hematological therapy and corticosteroid treatment showed higher NRM. Improvements in identifying and managing concurrent infections during SARS-CoV-2 are needed to further reduce morbimortality in hematologic patients. Highlights • Hematological patients with SARS-CoV-2 had a co-infection rate of 9% (30% with polymicrobial agents). • Ischemic cardiopathy, CAR-T therapy and pneumonia increase the risk of co-infection. • Co-infection significantly increases non-relapse mortality.