Publications by authors named "Jose A Garcia Marco"

The SRealCLL study described the occurrence of adverse events (AEs) and healthcare resource utilization in patients with chronic lymphocytic leukaemia (CLL) using artificial intelligence in a real-world scenario in Spain. We collected real-world data on patients with CLL from seven Spanish hospitals between January 2016 and December 2018, focusing on their AE and healthcare service utilization. Data extraction from electronic health records of 385,904 patients was performed using the EHRead technology, which is based on natural language processing and machine learning.

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JCO SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.

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Background: BTK inhibitors have been concurrently administered with anti-CD20 monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL). However, the optimal regimen for combining these two drugs remains pending.

Methods: This multi-center phase 2 study aimed to analyze whether consolidation with ofatumumab improved the response in patients with CLL receiving front-line treatment with ibrutinib.

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Diffuse large B-cell lymphoma (DLBCL) requires a complete staging at diagnosis that may have prognostic and therapeutic implications. The role of bone marrow (BM) biopsy (BMB) is controversial in the era of nuclear imaging techniques. We performed a comparative review of 25 studies focused on BM evaluation at DLBCL diagnosis, including at least two of the following techniques: BMB, flow cytometry, and positron emission tomography (PET-FDG).

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In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria.

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The SRealCLL study aimed to obtain real-world evidence on the clinical characteristics and treatment patterns of patients with chronic lymphocytic leukemia (CLL) using natural language processing (NLP). Electronic health records (EHRs) from seven Spanish hospitals (January 2016-December 2018) were analyzed using EHRead technology, based on NLP and machine learning. A total of 534 CLL patients were assessed.

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GABRIELL was a phase II single-arm study to evaluate the efficacy and safety of obinutuzumab plus bendamustine for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Seventy-two patients with active disease received treatment for up to six 28-day cycles. Overall response rate was 78.

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Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19.

Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries.

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Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19.

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Article Synopsis
  • * Recent studies using next-generation sequencing have highlighted significant mutations in genes like NOTCH1, SF3B1, and TP53 that are involved in crucial cellular functions like DNA repair and RNA processing.
  • * In our research, analyzing patients in the REM clinical trial, we found that, aside from mutations in the TP53 gene, other mutations do not significantly impact the effectiveness of maintenance therapy with rituximab following initial treatment with FCR.
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This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.

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Purpose: Among Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutinib, which we hypothesized would improve continuous therapy tolerability. We conducted an open-label, randomized, noninferiority, phase III trial comparing acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia (CLL).

Methods: Patients with previously treated CLL with centrally confirmed del(17)(p13.

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Background: Mechanisms driving the progression of chronic lymphocytic leukemia (CLL) from its early stages are not fully understood. The acquisition of molecular changes at the time of progression has been observed in a small fraction of patients, suggesting that CLL progression is not mainly driven by dynamic clonal evolution. In order to shed light on mechanisms that lead to CLL progression, we investigated longitudinal changes in both the genetic and immunological scenarios.

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Among the different biomarkers predicting response in chronic lymphocytic leukemia (CLL), the most influential parameters are the mutational status of the IGHV genes and the presence of TP53 gene disruptions. Nevertheless, these important assessments are not readily available in most centers dealing with CLL patients. To provide this molecular testing across the country, the Spanish Cooperative Group on CLL (GELLC) established a network of four analytical reference centers.

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Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included.

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Article Synopsis
  • Chronic lymphocytic leukemia (CLL) patients are more vulnerable to severe COVID-19, with 79% experiencing severe cases requiring oxygen or intensive care.
  • The study found that older age (≥65 years) was a key predictor of severe COVID-19 outcomes, while treatments like ibrutinib may offer some protection.
  • Among those with severe COVID-19, a significantly higher mortality rate was observed (36.4%) compared to mild cases (2.6%), indicating that CLL and immunodeficiency play critical roles in COVID-19 severity and outcomes.
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  • Increased angiogenesis in chronic lymphocytic leukemia (CLL) is linked to advanced disease, with CLL cells showing a pro-angiogenic gene expression pattern influenced by their environment.
  • MMP-9, a component of the microenvironment, was found to enhance MMP-9 expression and secretion in CLL cells, leading to increased endothelial cell proliferation.
  • MMP-9 also altered the expression of angiogenic-related genes, particularly decreasing TSP-1 and increasing VEGF, by involving specific molecular pathways, highlighting its role in CLL pathology.
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  • α4β1 integrin and VEGFR2 work together as a receptor complex that interacts with VEGF in chronic lymphocytic leukemia (CLL) cells.
  • This interaction suggests that α4β1 integrin has a new and significant role in the development of CLL.
  • The findings highlight how understanding these receptors could lead to better insights into CLL pathology and potential treatments.
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It has been postulated that monitoring measurable residual disease (MRD) could be used as a surrogate marker of progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients after treatment with immunochemotherapy regimens. In this study, we analyzed the outcome of 84 patients at 3 years of follow-up after first-line treatment with fludarabine, cyclophosphamide and rituximab (FCR) induction followed by 36 months of rituximab maintenance thearpy. MRD was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10 Eighty out of 84 evaluable patients (95.

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Article Synopsis
  • MMP-9 plays a significant role in the pathology of Chronic Lymphocytic Leukemia (CLL) by regulating cell survival, migration, and inducing cell arrest when expressed at high levels.
  • A study identified that MMP-9 alters the gene expression of specific genes in CLL cells, notably including CD99, which affects cell adhesion and migration.
  • The research highlights CD99 as a new therapeutic target that, when influenced by MMP-9, regulates CLL cell behavior and could lead to new treatment strategies.
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Chronic lymphocytic leukaemia is the most prevalent leukaemia in Western countries. It is an incurable disease characterized by a highly variable clinical course. Chronic lymphocytic leukaemia is an ideal model for studying clonal heterogeneity and dynamics during cancer progression, response to therapy and/or relapse because the disease usually develops over several years.

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  • Researchers found that MMP-9, when overexpressed, hinders the movement of chronic lymphocytic leukemia (CLL) cells, leading to studies on a mutant form of MMP-9 that doesn't break down proteins (MMP-9MutE).
  • In mouse models, these MMP-9MutE cells showed reduced ability to migrate to key areas like the spleen and bone marrow compared to control cells.
  • The study identified changes in cellular signaling pathways; MMP-9MutE cells had higher levels of PTEN and lower p-ERK, indicating that non-proteolytic functions of MMP-9 are important in CLL cell migration and may affect disease progression.
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Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing.

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