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1.
Haematologica ; 108(1): 110-121, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35770532

RESUMO

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P<0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P=0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P=0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P=0.195), 51% and 47% (P=0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lymphodepletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products.


Assuntos
Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Antígenos CD19 , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/terapia , Estudos Retrospectivos
2.
J Antimicrob Chemother ; 77(7): 2017-2023, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35466357

RESUMO

OBJECTIVES: To describe current resistance to the ß-lactams empirically recommended in the guidelines in bloodstream infection (BSI) episodes caused by Gram-negative bacilli (GNB). METHODS: Retrospective, multicentre cohort study of the last 50 BSI episodes in haematological patients across 14 university hospitals in Spain. Rates of inappropriate empirical antibiotic therapy (IEAT) and impact on mortality were evaluated. RESULTS: Of the 700 BSI episodes, 308 (44%) were caused by GNB, mainly Escherichia coli (141; 20.1%), Klebsiella spp. (56; 8%) and Pseudomonas aeruginosa (48; 6.9%). Among GNB BSI episodes, 80 (26%) were caused by MDR isolates. In those caused by Enterobacterales, 25.8% were ESBL producers and 3.5% were carbapenemase producers. Among P. aeruginosa BSI episodes, 18.8% were caused by MDR isolates. Overall, 34.7% of the isolated GNB were resistant to at least one of the three ß-lactams recommended in febrile neutropenia guidelines (cefepime, piperacillin/tazobactam and meropenem). Despite extensive compliance with guideline recommendations (91.6%), 16.6% of BSI episodes caused by GNB received IEAT, which was more frequent among MDR GNB isolates (46.3% versus 6.1%; P < 0.001). Thirty day mortality was 14.6%, reaching 21.6% in patients receiving IEAT. CONCLUSIONS: Current resistance to empirical ß-lactams recommended in febrile neutropenia guidelines is exceedingly high and IEAT rates are greater than desired. There is an urgent need to adapt guidelines to current epidemiology and better identify patients with a high risk of developing MDR GNB infection.


Assuntos
Bacteriemia , Neutropenia Febril , Infecções por Bactérias Gram-Negativas , Sepse , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Estudos de Coortes , Neutropenia Febril/tratamento farmacológico , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Pseudomonas aeruginosa , Estudos Retrospectivos , Sepse/tratamento farmacológico , Espanha/epidemiologia , beta-Lactamas/uso terapêutico
3.
Int Ophthalmol ; 42(9): 2711-2718, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35355170

RESUMO

PURPOSE: To evaluate the impact of trabecular micro bypass stents (iStent Inject) on refractive outcomes with toric intraocular lens (IOL) in glaucomatous eyes. METHODS: We identified glaucomatous eyes receiving a toric IOL between October 2017 and December 2020. Eyes with iStent implantation were included in the study group and eyes undergoing isolated phacoemulsification served as controls. Corrected and uncorrected visual acuity, manifest refraction, intraocular pressure (IOP), and number of hypotensive drugs three months after surgery were evaluated. RESULTS: 26 eyes comprised the study group and 41 eyes the control group. Mean postoperative refractive cylinder was 0.26D in the control and 0.11D in the iStent group, with 63% and 85% of eyes with a cylinder of 0 and 85% and 92% of eyes with a cylinder ≤ 0.5D respectively. The mean absolute difference between target and outcome spherical equivalent was 0.26D in the control and 0.22D in the iStent group, with all eyes within 0.75D of target. LogMar uncorrected postoperative vision in eyes targeted for emmetropia was 0.04 in the control and 0.03 in the iStent group. There was a statistically significant reduction in IOP and number of hypotensive drugs in both groups, with a mean decrease in IOP of 8.6% in the control and 15.7% in the iStent group. The number of hypotensive drugs dropped from 1.63 ± 0.80 to 1.34 ± 0.91 in the control group and from 2.12 ± 0.65 to 0.44 ± 0.71 in the iStent group. CONCLUSION: Toric IOLs provide predictable refractive outcomes in glaucomatous eyes undergoing combined phacoemulsification with iStent implantation, reducing postoperative spectacle dependence.


Assuntos
Astigmatismo , Catarata , Glaucoma , Lentes Intraoculares , Facoemulsificação , Humanos , Implante de Lente Intraocular , Refração Ocular , Stents
4.
Haematologica ; 106(9): 2325-2333, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32732356

RESUMO

In cases of treatment failure in acute myeloid leukemia (AML), the utility of mutational profiling in primary refractoriness and relapse is not established. We undertook a perspective study using next-generation sequencing (NGS) of clinical follow-up samples (n=91) from 23 patients with AML with therapeutic failure to cytarabine plus idarubicin or fludarabine. Cases of primary refractoriness to treatment were associated with a lower number of DNA variants at diagnosis than cases of relapse (median 1.67 and 3.21, respectively, p=0.029). The most frequently affected pathways in patients with primary refractoriness were signaling, transcription and tumor suppression, whereas methylation and splicing pathways were mainly implicated in relapsed patients. New therapeutic targets, either by an approved drug or within clinical trials, were not identified in any of the cases of refractoriness (0/10); however, 8 potential new targets were found in 5 relapsed patients (5/13) (p=0.027): 1 IDH2, 3 SF3B1, 2 KRAS, 1 KIT and 1 JAK2. Sixty-five percent of all variants detected at diagnosis were not detected at complete response (CR). Specifically, 100% of variants in EZH2, RUNX1, VHL, FLT3, ETV6, U2AF1, PHF6 and SF3B1 disappeared at CR, indicating their potential use as markers to evaluate minimal residual disease (MRD) for follow-up of AML. Molecular follow-up using a custom NGS myeloid panel of 32 genes in the post-treatment evaluation of AML can help in the stratification of prognostic risk, the selection of MRD markers to monitor the response to treatment and guide post-remission strategies targeting AML, and the selection of new drugs for leukemia relapse.


Assuntos
Leucemia Mieloide Aguda , Preparações Farmacêuticas , Evolução Clonal/genética , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Neoplasia Residual , Prognóstico , Recidiva
5.
Eur J Haematol ; 104(5): 400-408, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31804029

RESUMO

OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) is an aggressive heterogeneous lymphoma with standard treatment. However, 30%-40% of patients still fail, so we should know which patients are candidates for alternative therapies. IPI is the main prognostic score but, in the rituximab era, it cannot identify a very high-risk (HR) subset. The MD Anderson Cancer Center reported a score in the prerituximab era exclusively considering tumor-related variables: Tumor Score (TS). We aim to validate TS in the rituximab era and to analyze its current potential role. METHODS: From GELTAMO DLBCL registry, we selected those patients homogeneously treated with R-CHOP (n = 1327). RESULTS: Five-years PFS and OS were 62% and 74%. All variables retained an independent prognostic role in the revised TS (R-TS), identifying four different risk groups, with 5-years PFS of 86%, 71%, 50%, and very HR (28%). With a further categorization of three variables of the original TS (Ann Arbor Stage, LDH and B2M), we generated a new index that allowed an improvement in HR assessment. CONCLUSIONS: (a) All variables of the original TS retain an independent prognostic role, and R-TS remains predictive in the rituximab era; (b) R-TS and additional categorization of LDH, B2M, and AA stage (enhanced TS) increased the ability to identify HR subsets.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida , Doxorrubicina , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prednisona , Prognóstico , Sistema de Registros , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Vincristina , Adulto Jovem
6.
Eur J Haematol ; 105(5): 597-607, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32710500

RESUMO

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) in haematological patients (HP) has not been comprehensively reported. METHODS: We analysed 39 patients with SARS-CoV-2 infection and haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non-cancer patients with COVID-19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome. RESULTS: The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty-seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non-cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID-19 therapy were not predictors of outcome. CONCLUSION: Mortality of COVID-19 is significantly higher in patients with haematological malignancies compared to non-cancer patients. The impact of persistent viral shedding must be considered in order to re-start therapies and maintain infectious control measures.


Assuntos
COVID-19/complicações , COVID-19/mortalidade , Neoplasias Hematológicas/complicações , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , Estudos de Casos e Controles , Feminino , Neoplasias Hematológicas/sangue , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Linfoma/complicações , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Análise Multivariada , Pandemias , Fatores de Risco , SARS-CoV-2 , Espanha/epidemiologia
8.
Transplant Cell Ther ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069076

RESUMO

Chimeric antigen receptor (CAR)-T cell therapy is approved for the treatment of relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, elderly patients might not be candidates for this therapy due to its toxicity, and criteria for candidate selection are lacking. Our aim was to analyze efficacy and toxicity results of CAR-T cell therapy in the population of patients 70 years and older as compared to those obtained in younger patients in the real-world setting. A multicentric retrospective study was performed including patients with R/R aggressive LBCL who received commercial CAR-T cell therapy with either tisagenlecleucel or axicabtagene ciloleucel within the Spanish Group of Hematopoietic Transplant and Cell Therapy/Spanish Group of Lymphomas and Autologous Transplant (GETH-TC/GELTAMO) centers between 2019 and 2023. As of August 2023, 442 adult patients with aggressive LBCL underwent apheresis for CAR-T cell therapy as third or subsequent line and follow-up data was collected. Of 412 infused patients, 71 (17%) were 70 years or older. Baseline characteristics, product selection, and characteristics at apheresis (including disease status, Ann Arbor stage, revised international prognosis index (R-IPI), bulky disease, lactate dehydrogenase [LDH] and ECOG [Eastern Cooperative Group performance status]) were comparable between groups. Median time from both approval to infusion and apheresis to infusion did not differ. No differences were found between groups in overall and complete response rates at 1 and 3 months. With a median follow-up of 12.2 months (range 1-44), 12-month progression-free survival (PFS) and overall survival (OS) were comparable between groups (35.2% in <70 years vs. 35.9% in ≥70 years (P = .938) and 51.1% and 52.1% (P = .885), respectively). Age ≥70 years did not affect PFS (hazard ratio (HR) 0.98, P = .941) and OS (HR 0.97, P = .890) in the univariate and multivariate analysis. Cytokine release syndrome (CRS) was observed in 82% of patients <70 years old and 84.5% in ≥ 70 years old (P = .408). Grade ≥3 CRS was more frequent in the older group (5% vs. 15%, P = .002). In the multivariate analysis, age ≥70 years was associated with an increased risk of grade ≥3 CRS (OR 3.7, P = .013). No differences were observed in terms of overall neurotoxicity (35% vs. 42%, P = .281) or grade ≥3 (12% vs. 17%, P = .33). The proportion of patients with infections, admission to the intensive care unit within the first month, and non-relapse mortality were similar between both groups. CAR-T cell therapy in patients older than 70 years showed similar efficacy to that observed in younger patients in the real-world setting. However, age ≥70 years was an independent risk factor for grades 3-4 CRS. The need for additional strategies to reduce toxicity in this population should be addressed in future studies.

9.
Front Immunol ; 14: 1188818, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342332

RESUMO

Background: CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. Method: Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death. Results: After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression. Conclusion: This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.


Assuntos
DNA Tumoral Circulante , Linfoma Folicular , Receptores de Antígenos Quiméricos , Humanos , Feminino , DNA Tumoral Circulante/genética , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva Local de Neoplasia , Terapia Baseada em Transplante de Células e Tecidos
12.
Cancers (Basel) ; 15(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36672481

RESUMO

For the treatment of Multiple Myeloma, proteasome inhibitors are highly efficient and widely used, but resistance is a major obstacle to successful therapy. Several underlying mechanisms have been proposed but were only reported for a minority of resistant patients. The proteasome is a large and complex machinery. Here, we focus on the AAA ATPases of the 19S proteasome regulator (PSMC1-6) and their implication in PI resistance. As an example of cancer evolution and the acquisition of resistance, we conducted an in-depth analysis of an index patient by applying FISH, WES, and immunoglobulin-rearrangement sequencing in serial samples, starting from MGUS to newly diagnosed Multiple Myeloma to a PI-resistant relapse. The WES analysis uncovered an acquired PSMC2 Y429S mutation at the relapse after intensive bortezomib-containing therapy, which was functionally confirmed to mediate PI resistance. A meta-analysis comprising 1499 newly diagnosed and 447 progressed patients revealed a total of 36 SNVs over all six PSMC genes that were structurally accumulated in regulatory sites for activity such as the ADP/ATP binding pocket. Other alterations impact the interaction between different PSMC subunits or the intrinsic conformation of an individual subunit, consequently affecting the folding and function of the complex. Interestingly, several mutations were clustered in the central channel of the ATPase ring, where the unfolded substrates enter the 20S core. Our results indicate that PSMC SNVs play a role in PI resistance in MM.

13.
Microbiol Spectr ; 11(4): e0067423, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37367629

RESUMO

Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the ß-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate ß-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed. IMPORTANCE Bloodstream infection (BSI) caused by P. aeruginosa is related with an elevated morbidity and mortality in neutropenic patients. For this reason, optimal antipseudomonal coverage has been the basis of all historical recommendations in the empirical treatment of febrile neutropenia. However, in recent years the emergence of multiple types of antibiotic resistances has posed a challenge in treating infections caused by this microorganism. In our study we postulated that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines. This observation is associated with frequent IEAT and increased mortality. Consequently, there is a need for a new therapeutic strategy.


Assuntos
Bacteriemia , Neoplasias Hematológicas , Infecções por Pseudomonas , Sepse , Humanos , Antibacterianos/uso terapêutico , Pseudomonas aeruginosa , Estudos de Coortes , Estudos Retrospectivos , Infecções por Pseudomonas/tratamento farmacológico , Bacteriemia/tratamento farmacológico , Meropeném , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Sepse/tratamento farmacológico
14.
J Ophthalmol ; 2021: 9935983, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221497

RESUMO

PURPOSE: To report visual function and self-reported satisfaction of patients with glaucoma and dry age-related macular degeneration (dAMD) implanted with multifocal intraocular lenses (MIOL). METHODS: Patients with glaucoma or dAMD as well as healthy individuals implanted with MIOL were invited to participate. Explorations performed were uncorrected and corrected distance visual acuity (UDVA and CDVA), low-contrast visual acuity (LCVA), binocular contrast sensitivity, and defocus curves. Patients completed the Catquest-9 questionnaire and reported on the presence of dysphotopsias and the need for spectacles. RESULTS: 38 subjects were included: 11 in the healthy/control group and 9 each in the preperimetric glaucoma, perimetric glaucoma, and dAMD groups. Controls had statistically better monocular UDVA, CDVA, and LCVA than patients with glaucoma and dAMD, as well as better binocular acuity in the defocus curves between -2.00 D and +0.50 D. Differences between controls and patients with preperimetric glaucoma were not statistically significant. Between -3.0 D and +0.5 D, all groups except dAMD achieved acuities better than 0.2 logMAR. Patients with dAMD had worse contrast sensitivity than all others for 3 cycles per degree (cpd), and patients with glaucoma had worse values than all others for 12 cpd; other differences did not reach statistical significance. Healthy subjects and patients with preperimetric glaucoma perceived halos more often than patients with glaucoma or dAMD, while suffering less from glare. Patients with glaucoma and dAMD found more difficulties when driving at night and required spectacles for near more often than the other subjects. Patients with dAMD were less satisfied with their vision. CONCLUSIONS: MIOLs may be implanted in patients with preperimetric glaucoma with little fear of patient dissatisfaction. In glaucoma and dAMD, MIOLs might be considered with caution, after explaining the increased risk of glare and the higher need for spectacle correction for reading.

15.
J Hematol Oncol ; 14(1): 126, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404440

RESUMO

The assessment of measurable residual disease (MRD) in bone marrow has proven of prognostic relevance in patients with multiple myeloma (MM). Nevertheless, and unlike other hematologic malignancies, the use of MRD results to make clinical decisions in MM has been underexplored to date. In this retrospective study, we present the results from a multinational and multicenter series of 400 patients with MRD monitoring during front-line therapy with the aim of exploring how clinical decisions made based on those MRD results affected outcomes. As expected, achievement of MRD negativity at any point was associated with improved PFS versus persistent MRD positivity (median PFS 104 vs. 45 months, p < 0.0001). In addition, however, 67 out of 400 patients underwent a clinical decision (treatment discontinuation, intensification or initiation of a new therapy) based on MRD results. Those patients in whom a treatment change was made showed a prolonged PFS in comparison with those 333 patients in which MRD results were not acted upon (respectively, mPFS 104 vs. 62 months, p = 0.005). In patients who achieved MRD negativity during maintenance (n = 186) on at least one occasion, stopping therapy in 24 patients vs. continuing in 162 did not alter PFS (mPFS 120 months vs. 82 months, p = 0.1). Most importantly, however, in patients with a positive MRD during maintenance (n = 214), a clinical decision (either intensification or change of therapy) (n = 43) resulted in better PFS compared to patients in whom no adjustment was made (n = 171) (mPFS NA vs. 39 months, p = 0.02). Interestingly, there were no significant differences when MRD was assessed by flow cytometry or by next-generation sequencing. Herein, we find that MRD is useful in guiding clinical decisions during initial therapy and has a positive impact on PFS in MM patients. This potentially opens a new dimension for the use of MRD in MM, but this role still remains to be confirmed in prospective, randomized clinical trials.


Assuntos
Mieloma Múltiplo/diagnóstico , Neoplasia Residual/diagnóstico , Tomada de Decisão Clínica , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Neoplasia Residual/terapia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
16.
Blood Cancer J ; 8(10): 91, 2018 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-30504932

RESUMO

Over half of chronic myeloid leukemia (CML) patients in deep molecular response do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in clinical trials, but its applicability in the real-life setting remains unsettled. We describe the outcomes after TKI discontinuation in a nationwide series of 236 CML patients. Median follow-up from treatment discontinuation was 21.5 months and 5 patients died from CML-unrelated causes. TKI therapy was reinitiated due to MMR loss (n = 52), increase ≥ 1 log in BCR-ABL transcript level without losing MMR (n = 12), patient preference (n = 2), and withdrawal syndrome (n = 1). Treatment-free remission rate at 4 years was 64% (95% confidence interval, CI: 55%-72%). Cumulative incidence of molecular recurrence at 3 years was 33% (95% CI: 26%-38%). TKI treatment for < 5 years and MR4.5 duration shorter than 4 years were both associated with higher incidence of molecular recurrence. No patient had disease progression. Response status at last control was: MR4.5 (n = 196), MR4 (n = 15), MMR (n = 14), complete cytogenetic response (n = 10), and other (n = 1). A significant increase in Hb and cholesterol levels was observed after imatinib withdrawal. Our results demonstrate that TKI treatment discontinuation is feasible in real-life clinical practice.


Assuntos
Anticarcinógenos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Anticarcinógenos/administração & dosagem , Anticarcinógenos/efeitos adversos , Biomarcadores , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Recidiva , Resultado do Tratamento
17.
Tuberculosis (Edinb) ; 93(4): 456-60, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23680290

RESUMO

BACKGROUND: Immigrants may not transmit tuberculosis (TB) more than indigenous patients. The objective was to study the prevalence of TB infection among contacts of immigrant and indigenous TB patients and the risk factors associated with latent TB infection. METHODS: Contacts of TB cases recorded in 2005 and 2006 were surveyed using a standardized Health Department questionnaire. Infections were diagnosed using the tuberculin skin test (TST) (cut-off ≥ 5 mm). The risk of infection was determined by multivariate logistic regression and the adjusted odds ratios (aOR) with the 95% confidence intervals (CI) were calculated. RESULTS: The study of contacts was completed in 1329 cases of TB. The prevalence of infection was 32.3% (3038/9406) in all contacts, 41.4% in contacts of immigrant cases and 29.2% in contacts of indigenous cases. In the multivariate analysis, immigrant index cases were not associated with an increased risk (aOR = 0.9; 95%CI: 0.8-1.0). The prevalence of TST conversion was 10.0% (296/2969) in all contacts, 11.2% in immigrant contacts and 9.7% in indigenous contacts (p = 0.158). CONCLUSIONS: Immigrants do not transmit TB more than indigenous TB patients. Infections which may have occurred in the countries of origin of immigrants were detected by the systematic study of contacts.


Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Tuberculose/transmissão , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Busca de Comunicante/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Tuberculose Latente/diagnóstico , Tuberculose Latente/etnologia , Tuberculose Latente/transmissão , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Espanha/epidemiologia , Teste Tuberculínico , Tuberculose/diagnóstico , Tuberculose/etnologia
19.
Salud(i)ciencia (Impresa) ; 21(5): 500-504, ago.2015. tab
Artigo em Espanhol | LILACS | ID: lil-785409

RESUMO

Evaluar la eficacia del tratamiento corticoideo tópico prolongado en pacientes operados con LASIK hipermetrópico. Material y métodos: Se realizó un estudio prospectivo, de observación y enmascarado. Los pacientes candidatos a cirugía LASIK para la corrección de baja y moderada hipermetropía fueron asignados aleatoriamente a recibir tratamiento tópico corticoideo (dexametasona) durante una semana (grupo control) o un mes (dexametasona, la primera semana, y fluorometalona, las tres siguientes),en el grupo de estudio. Se comparó la refracción final manifiesta en ambos grupos. Resultados:Analizamos 105 ojos en cada grupo (estudio y control). El equivalente esférico medio preoperatorioera 3.17 desviación estándar (DE) ± 2.82 DE y 3.39 DE ± 2.65 DE en los grupos de estudio y control, respectivamente (p = 0.6). La refracción final manifiesta a los tres meses fue 0.62 DE ± 0.68 DE y 0.6 DE± 0.3 DE en el grupo de estudio y control, respectivamente (p = 0.6). Conclusión: La regresión refractivatras el LASIK hipermetrópico no parece poder modularse por el mayor o menor tratamiento corticoideotópico...


Assuntos
Humanos , Cirurgia Geral , Hiperopia , Acuidade Visual , Corticosteroides , Esteroides , Olho , Visão Ocular
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