Publications by authors named "A Teruel"

76 Publications

Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial.

Blood Cancer J 2021 May 21;11(5):101. Epub 2021 May 21.

Hospital Clínico Universitario de Valencia, Valencia, Spain.

Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0-54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3-4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.
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http://dx.doi.org/10.1038/s41408-021-00490-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139975PMC
May 2021

Ten-year assessment of a cancer fast-track programme to connect primary care with oncology: reducing time from initial symptoms to diagnosis and treatment initiation.

ESMO Open 2021 May 11;6(3):100148. Epub 2021 May 11.

Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain. Electronic address:

Background: Cancer is the second leading cause of mortality worldwide. Integrating different levels of care by implementing screening programmes, extending diagnostic tools and applying therapeutic advances may increase survival. We implemented a cancer fast-track programme (CFP) to shorten the time between suspected cancer symptoms, diagnosis and therapy initiation.

Patients And Methods: Descriptive data were collected from the 10 years since the CFP was implemented (2009-2019) at the Clinico-Malvarrosa Health Department in Valencia, Spain. General practitioners (GPs), an oncology coordinator and 11 specialists designed guidelines for GP patient referral to the CFP, including criteria for breast, digestive, gynaecological, lung, urological, dermatological, head and neck, and soft tissue cancers. Patients with enlarged lymph nodes and constitutional symptoms were also considered. On identifying patients with suspected cancer, GPs sent a case proposal to the oncology coordinator. If criteria were met, an appointment was quickly made with the patient. We analysed the timeline of each stage of the process.

Results: A total of 4493 suspected cancer cases were submitted to the CFP, of whom 4019 were seen by the corresponding specialist. Cancer was confirmed in 1098 (27.3%) patients: breast cancer in 33%, urological cancers in 22%, gastrointestinal cancer in 19% and lung cancer in 15%. The median time from submission to cancer testing was 11 days, and diagnosis was reached in a median of 19 days. Treatment was started at a median of 34 days from diagnosis.

Conclusions: The findings of this study show that the interval from GP patient referral to specialist testing, cancer diagnosis and start of therapy can be reduced. Implementation of the CFP enabled most patients to begin curative intended treatment, and required only minimal resources in our setting.
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http://dx.doi.org/10.1016/j.esmoop.2021.100148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136438PMC
May 2021

Multiple small bowel perforations during the treatment of primary intestinal extranodal natural killer/T-cell lymphoma, nasal type.

Br J Haematol 2021 Jun 29;193(5):e39-e42. Epub 2021 Apr 29.

Department of General Surgery, Hospital Clínico, Liver, Biliary and Pancreatic Unit, University of Valencia, Biomedical Research Institute INCLIVA, Valencia, Spain.

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http://dx.doi.org/10.1111/bjh.17229DOI Listing
June 2021

New Insights of Oral Colonic Drug Delivery Systems for Inflammatory Bowel Disease Therapy.

Int J Mol Sci 2020 Sep 5;21(18). Epub 2020 Sep 5.

Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, 46022 Valencia, Spain.

Colonic Drug Delivery Systems (CDDS) are especially advantageous for local treatment of inflammatory bowel diseases (IBD). Site-targeted drug release allows to obtain a high drug concentration in injured tissues and less systemic adverse effects, as consequence of less/null drug absorption in small intestine. This review focused on the reported contributions in the last four years to improve the effectiveness of treatments of inflammatory bowel diseases. The work concludes that there has been an increase in the development of CDDS in which pH, specific enzymes, reactive oxygen species (ROS), or a combination of all of these triggers the release. These delivery systems demonstrated a therapeutic improvement with fewer adverse effects. Future perspectives to the treatment of this disease include the elucidation of molecular basis of IBD diseases in order to design more specific treatments, and the performance of more in vivo assays to validate the specificity and stability of the obtained systems.
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http://dx.doi.org/10.3390/ijms21186502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555849PMC
September 2020

Biological and clinical significance of dysplastic hematopoiesis in patients with newly diagnosed multiple myeloma.

Blood 2020 06;135(26):2375-2387

Hospital Universitario de Canarias, Tenerife, Spain.

Risk of developing myelodysplastic syndrome (MDS) is significantly increased in both multiple myeloma (MM) and monoclonal gammopathy of undetermined significance, suggesting that it is therapy independent. However, the incidence and sequelae of dysplastic hematopoiesis at diagnosis are unknown. Here, we used multidimensional flow cytometry (MFC) to prospectively screen for the presence of MDS-associated phenotypic alterations (MDS-PA) in the bone marrow of 285 patients with MM enrolled in the PETHEMA/GEM2012MENOS65 trial (#NCT01916252). We investigated the clinical significance of monocytic MDS-PA in a larger series of 1252 patients enrolled in 4 PETHEMA/GEM protocols. At diagnosis, 33 (11.6%) of 285 cases displayed MDS-PA. Bulk and single-cell-targeted sequencing of MDS recurrently mutated genes in CD34+ progenitors (and dysplastic lineages) from 67 patients revealed clonal hematopoiesis in 13 (50%) of 26 cases with MDS-PA vs 9 (22%) of 41 without MDS-PA; TET2 and NRAS were the most frequently mutated genes. Dynamics of MDS-PA at diagnosis and after autologous transplant were evaluated in 86 of 285 patients and showed that in most cases (69 of 86 [80%]), MDS-PA either persisted or remained absent in patients with or without MDS-PA at diagnosis, respectively. Noteworthy, MDS-associated mutations infrequently emerged after high-dose therapy. Based on MFC profiling, patients with MDS-PA have altered hematopoiesis and T regulatory cell distribution in the tumor microenvironment. Importantly, the presence of monocytic MDS-PA at diagnosis anticipated greater risk of hematologic toxicity and was independently associated with inferior progression-free survival (hazard ratio, 1.5; P = .02) and overall survival (hazard ratio, 1.7; P = .01). This study reveals the biological and clinical significance of dysplastic hematopoiesis in newly diagnosed MM, which can be screened with moderate sensitivity using cost-effective MFC.
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http://dx.doi.org/10.1182/blood.2019003382DOI Listing
June 2020