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BACKGROUND: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. RESULTS: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. CONCLUSION: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.
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Proteína BRCA2 , Neoplasias da Mama , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Feminino , Mutação em Linhagem Germinativa/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/epidemiologia , Colômbia/epidemiologia , Pessoa de Meia-Idade , Adulto , Proteína BRCA2/genética , Proteína BRCA1/genética , Sequenciamento do Exoma , Idoso , Testes Genéticos/métodos , Proteínas Mutadas de Ataxia Telangiectasia/genéticaRESUMO
PURPOSE: Multiple myeloma (MM) is a highly heterogeneous, incurable disease most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the very young population are scarce. PATIENTS AND METHODS: We analyzed clinical characteristics, response to treatment, and survival in 103 patients with newly diagnosed MM age 40 years or younger compared with 256 patients age 41-50 years and 957 patients age 51 years or older. RESULTS: There were no statistical differences in sex, isotype, International Scoring System, renal involvement, hypercalcemia, anemia, dialysis, bony lesions, extramedullary disease, and lactate dehydrogenase (LDH). The most used regimen in young patients was cyclophosphamide, bortezomib, dexamethasone, followed by cyclophosphamide, thalidomide, dexamethasone and bortezomib, thalidomide, dexamethasone. Of the patients age 40 years or younger, only 53% received autologous stem-cell transplant (ASCT) and 71.1% received maintenance. There were no differences in overall survival (OS) in the three patient cohorts. In the multivariate analysis, only high LDH, high cytogenetic risk, and ASCT were statistically associated with survival. CONCLUSION: In conclusion, younger patients with MM in Latin America have similar clinical characteristics, responses, and OS compared with the elderly.
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Mieloma Múltiplo , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/uso terapêutico , Talidomida/uso terapêutico , América Latina/epidemiologia , Resultado do Tratamento , Dexametasona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Ciclofosfamida/uso terapêuticoRESUMO
To describe the population with early malignant melanoma, we performed a cohort study on the basis of the Epidemiological Registry of Malignant Melanoma in Colombia-Asociacion Colombiana de Hematologia y Oncologia. From January 2011 until December 2021, 759 patients were included; the average age was 66 years, 57% were women, acral lentiginous histology was found in 27.8% of patients, and the median follow-up was 36.5 months. The prognostic factors for overall survival in our population are Eastern Cooperative Oncology Group 3-4 (hazard ratio [HR], 13.8), stage III (HR, 5.07), received radiotherapy (HR, 3.38), ulceration on histology (HR, 2.68), chronic sun exposure (HR, 2.3), low income (HR, 2.04), previous local surgery (HR, 0.27), and have received adjuvant treatment (HR, 0.41).
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Melanoma , Humanos , Feminino , Idoso , Masculino , Estudos de Coortes , Prognóstico , Colômbia/epidemiologia , América Latina , Melanoma/diagnóstico , Melanoma/epidemiologia , Melanoma/terapia , Sistema de Registros , Melanoma Maligno CutâneoRESUMO
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan is the first C3-targeted therapy approved for adults with PNH (United States), adults with PNH with inadequate response or intolerance to a C5 inhibitor (Australia), and adults with anemia despite C5-targeted therapy for ≥3 months (European Union). PRINCE was a phase 3, randomized, multicenter, open-label, controlled study to evaluate the efficacy and safety of pegcetacoplan vs control (supportive care only; eg, blood transfusions, corticosteroids, and supplements) in complement inhibitor-naive patients with PNH. Eligible adults receiving supportive care only for PNH were randomly assigned and stratified based on their number of transfusions (<4 or ≥4) 12 months before screening. Patients received pegcetacoplan 1080 mg subcutaneously twice weekly or continued supportive care (control) for 26 weeks. Coprimary end points were hemoglobin stabilization (avoidance of >1-g/dL decrease in hemoglobin levels without transfusions) from baseline through week 26 and lactate dehydrogenase (LDH) change at week 26. Overall, 53 patients received pegcetacoplan (n = 35) or control (n = 18). Pegcetacoplan was superior to control for hemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1%; 95% confidence interval [CI], 57.2-89.0; P < .0001) and change from baseline in LDH (least square mean change: pegcetacoplan, -1870.5 U/L; control, -400.1 U/L; difference, -1470.4 U/L; 95% CI, -2113.4 to -827.3; P < .0001). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals were observed. Pegcetacoplan rapidly and significantly stabilized hemoglobin and reduced LDH in complement inhibitor-naive patients and had a favorable safety profile. This trial was registered at www.clinicaltrials.gov as NCT04085601.
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Hemoglobinúria Paroxística , Adulto , Humanos , Hemoglobinúria Paroxística/tratamento farmacológico , Inativadores do Complemento/efeitos adversos , Hemólise , Anticorpos Monoclonais Humanizados/efeitos adversos , Hemoglobinas , L-Lactato DesidrogenaseRESUMO
PURPOSE: Waldenstrom Macroglobulinemia (WM) is a rare lymphoma with distinct clinical features, and data from Latin American patients are lacking. Therefore, we aim to investigate the clinical, therapy, and outcome patterns of WM in Latin America. METHODS: We retrospectively analyzed patients with WM diagnosed between 1991 and 2019 from 24 centers in seven Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 159 cases (median age 67 years, male 62%). Most patients (95%) were symptomatic at diagnosis. The International Prognostic Scoring System for WM (IPSSWM) at diagnosis was available in 141 (89%) patients (high-risk 40%, intermediate-risk 37%, and low-risk 23%). Twenty-seven (17%) patients were tested for MYD88L265P, with 89% (n = 24 of 27) carrying the mutation. First-line and second-line therapies were administered to 142 (89%) and 53 (33%) patients, respectively. Chemoimmunotherapy was the most commonly used first-line (66%) and second-line (45%) approach; only 18 (11%) patients received ibrutinib. With a median follow-up of 69 months, the 5-year OS rate was 81%. In treated patients, the 5-year OS and PFS rates were 78% and 59%, respectively. High-risk IPSSWM at treatment initiation was an independent risk factor for OS (adjusted hazard ratio: 4.73, 95% CI, 1.67 to 13.41, P = .003) and PFS (adjusted hazard ratio: 2.43, 95% CI, 1.31 to 4.50, P = .005). CONCLUSION: In Latin America, the management of WM is heterogeneous, with limited access to molecular testing and novel agents. However, outcomes were similar to those reported internationally. We validated the IPSSWM score as a prognostic factor for OS and PFS. There is an unmet need to improve access to recommended diagnostic approaches and therapies in Latin America.
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Macroglobulinemia de Waldenstrom , Idoso , Humanos , América Latina/epidemiologia , Masculino , Mutação , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/uso terapêutico , Estudos Retrospectivos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/terapiaRESUMO
INTRODUCTION/BACKGROUND: Multiple Myeloma (MM) is a plasma cell derived clonal disorder that represents around 1% of all newly diagnosed neoplasms. Limited data regarding MM treatment in Latin America is available, and access to novel agents for a substantial portion of the population is limited by their high costs. MATERIALS (OR PATIENTS) AND METHODS: RENEHOC is a bidirectional (retrospective and prospective) multicenter observational registry of hematological malignancies in Colombia. MM patients included up to July 2020 were analyzed on this report. RESULTS: 890 are reported with a median follow-up of 18 months (IQR: 7-42 months). Patients were classified by age group (≤ or > 65 years). Median age at diagnosis was 67 years (IQR: 59-75 years) and 47.1% of patients were women. 709 patients (79.6%) received Bortezomib-based schemes as part of the first line. Two hundred and fifty-two patients (28.3%) were consolidated with Autologous Stem Cell Transplantation (ASCT) in first-line. ASCT consolidation and age were the main independent factors influencing outcomes; in the non-ASCT cohort, 5-year overall survival was 48.7% (CI 41.8-55.2) compared to 80.7% (CI 73-86.4) in ASCT patients. CONCLUSION: This data depicts the reality of MM in Colombia, which likely reflects other Latin American countries, where access barriers to diagnosis and treatment are echoed in advanced stage diagnosis and a low rate of transplants. These seem to negatively impact survival despite the availability of most novel drugs approved for this disease. Thus, emphasizing the paradox that prevails in most of the region: availability without equitable access.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Idoso , Bortezomib/uso terapêutico , Colômbia/epidemiologia , Feminino , Humanos , Masculino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Transplante AutólogoRESUMO
Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82], p < 0.01; 1-year OS 53 vs. 27%, respectively, p = 0.012). Combination zidovudine and interferon-alpha (AZT-IFN) yielded high response rates (overall response, OR = 100%, n = 8; complete response 62.5%) compared to chemotherapy (OR = 33.3%, n = 12/36). In conclusion, cutaneous involvement was associated with better survival in Latin American patients with ATLL. AZT-IFN demonstrated encouraging responses in ATLL patients with cutaneous involvement.
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Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Neoplasias Cutâneas , Adulto , Humanos , Interferon-alfa/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/patologia , Linfoma/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS: We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS: We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone-like regimen (P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION: This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.
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Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Argentina , Chile , Colômbia , Humanos , América Latina/epidemiologia , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Pessoa de Meia-Idade , Peru/epidemiologiaRESUMO
INTRODUCTION: The ACHOCC-19 study was performed to characterize COVID-19 infection in a Colombian oncological population. METHODOLOGY: Analytical cohort study of patients with cancer and COVID-19 infection in Colombia. From April 1 to October 31, 2020. Demographic and clinical variables related to cancer and COVID-19 infection were collected. The primary outcome was 30-day mortality from all causes. The association between the outcome and the prognostic variables was analyzed using logistic regression models and survival analysis with Cox regression. RESULTS: The study included 742 patients; 72% were >51 years. The most prevalent neoplasms were breast (132, 17.77%), colorectal (92, 12.34%), and prostate (81, 10.9%). Two hundred twenty (29.6%) patients were asymptomatic and 96 (26.3%) died. In the bivariate descriptive analysis, higher mortality occurred in patients who were >70 years, patients with lung cancer, ≥2 comorbidities, former smokers, receiving antibiotics, corticosteroids, and anticoagulants, residents of rural areas, low socioeconomic status, and increased acute-phase reactants. In the logistic regression analysis, higher mortality was associated with Eastern Cooperative Oncology Group performance status (ECOG PS) 3 (odds ratio [OR] 28.67; 95% confidence interval [CI], 8.2-99.6); ECOG PS 4 (OR 20.89; 95% CI, 3.36-129.7); two complications from COVID-19 (OR 5.3; 95% CI, 1.50-18.1); and cancer in progression (OR 2.08; 95% CI, 1.01-4.27). In the Cox regression analysis, the statistically significant hazard ratios (HR) were metastatic disease (HR 1.58; 95% CI, 1.16-2.16), cancer in progression (HR 1.08; 95% CI, 1.24-2.61) cancer in partial response (HR 0.31; 95% CI, 0.11-0.88), use of steroids (HR 1.44; 95% CI, 1.01-2.06), and use of antibiotics (HR 2.11; 95% CI, 1.47-2.95). CONCLUSION: In our study, patients with cancer have higher mortality due to COVID-19 infection if they have active cancer, metastatic or progressive cancer, ECOG PS >2, and low socioeconomic status. IMPLICATIONS FOR PRACTICE: This study's findings raise the need to carefully evaluate patients with metastatic cancer, in progression, and with impaired Eastern Cooperative Oncology Group status to define the relevance of cancer treatment during the pandemic, consider the risk/benefit of the interventions, and establish clear and complete communication with the patients and their families about the risk of complications. There is also the importance of offering additional support to patients with low income and residence in rural areas so that they can have more support during cancer treatment.
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COVID-19 , Neoplasias Pulmonares , Estudos de Coortes , Humanos , América Latina , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Masculino , SARS-CoV-2RESUMO
Abstract Introduction Gaucher's disease (GD) is an autosomal-recessive lysosomal storage disorder that results from hereditary deficiency of the acid glucocerebrosidase enzyme, encoded by the GBA gene necessary for the degradation of glucosylceramide. Objective molecularly characterize the variants found in the GBA gene present in patients from the Southwest of Colombia with GD. Material and methods 19 patients were included in the study, clinically and enzymatically diagnosed with GD. A molecular analysis of the GBA gene was performed and the variants were subsequently searched in different population and clinical databases. A bioinformatic analysis was performed. Results The variants in the GBA gene reported were classified into: 14/19 homozygous patients, 4/19 compound heterozygote and 1/19 heterozygous. The presence of 7 variants coding for 8 different genotypes was reported. Also the known mutations like Asn409Ser, p.Leu483Pro, p.Lys237Glu, p.Glu427Lys, and p.Arg535His were identified in these patients. The most frequent genotype was p. Asn409Ser / Asn409Ser (36%). All the variants presented a pathogenic clinical significance. Conclusion The given study will make it possible to understand the susceptibility to GD in the population. This can help maintain the health quotient of the population through premarital counseling and therefore minimize the burden of disease among the population.
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Resumen La enfermedad por COVID-19 fue detectada a finales de 2019 en Wuhan, China. Debido a su rápida propagación fue declarada emergencia sanitaria de forma inicial y luego de identificar casos fuera de China con transmisión autóctona y caracterizado por una mortalidad considerablemente alta en países como Italia y España, fue declarada pandemia por la Organización Mundial de la Salud. Se ha evidenciado que los pacientes mayores y con antecedentes de enfermedades crónicas incluido el cáncer desarrollan una enfermedad severa, presentando mayor riesgo de mortalidad por SARS-CoV2/ COVID-19. Lo anterior es por supuesto especialmente importante en el manejo de pacientes con Mieloma Múltiple (MM), generando en el personal Médico nuevos desafíos, oportunidades de mejora y aprendizajes, que aporten al análisis riesgo-beneficio del tratamiento inmunodepresor en este tipo de patologías. El consenso tiene como objetivo brindar orientación sobre el manejo de pacientes con MM en estos momentos donde el profesional de la salud requiere información para llevar a cabo terapias eficientes en el cuidado del paciente.
Abstract COVID-19 disease was detected in late 2019 in Wuhan, China. Due to its rapid spread, it was initially declared a health emergency, but after cases with indigenous transmission were identified outside China, characterized by considerably high mortality in countries such as Italy and Spain, it was declared a pandemic by the World Health Organization. It has been shown that elderly patients with a history of chronic diseases, including cancer, develop a severe disease, presenting a higher risk of mortality from SARS-CoV2 / COVID-19. This becomes especially important in the management of patients with Multiple Myeloma (MM), generating new challenges, opportunities for improvement and learning opportunities in the health professionals, which will contribute to the risk-benefit analysis of immunosuppressive treatment for this type of pathology. The consensus aims to provide guidance for the management of patients with MM in these times when the health professional requires information to deliver efficient therapies in patient care.
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Humanos , Consenso , COVID-19 , Mieloma Múltiplo , TerapêuticaRESUMO
Resumen Ante la pandemia COVID 19, declarada en marzo de 2020 por la Organización Mundial de la Salud (OMS), desde la Asociación Colombiana de Hematología y Oncología (ACHO) hemos venido emitiendo comunicaciones destinadas a orientar a los profesionales de la salud implicados en el tratamiento de pacientes hematológicos y oncológicos. Consideramos importante realizar una nueva actualización dada la fase de mitigación de la pandemia que actualmente estamos enfrentando y ante el planteamiento gubernamental de desdescalonamiento progresivo, de la cuarentena. Estas recomendaciones no pretenden imponer una conducta única pues entendemos que cada caso es particular y debe actuarse individualizando a cada situación específica. Están basadas en documentos emitidos por asociaciones científicas oncológicas y hematológicas reconocidas y son susceptibles de sufrir modificaciones a medida que se disponga de mayor información.
Abstract In response to the Covid-19 pandemic, declared in March 2020 by the World Health Organization (WHO), the Colombian Association of Hematology and Oncology (ACHO) has been issuing communications aimed at providing guidance to health professionals involved in the treatment of hematological and oncological patients. Considering the pandemic mitigation phase we are currently facing, and the government's approach to progressively tapering-off the quarantine, we deem it important to release a new update. These recommendations are not intended to impose a single conduct, since we understand that each case has particular characteristics and therefore it must be acted upon by individualizing each specific situation. The recommendations are based on documents issued by well-known cancer and hematological scientific associations, and are subject to change as more information becomes available.
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Humanos , Neoplasias Hematológicas , Pandemias , Terapêutica , Saúde , HematologiaRESUMO
The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , América Latina/epidemiologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Transplante Autólogo , Resultado do TratamentoRESUMO
INTRODUCTION: We aimed at investigating the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in 2 independent cohorts of Latin American patients with diffuse large B-cell lymphoma (DLBCL) treated with chemoimmunotherapy. PATIENTS AND METHODS: The learning cohort was composed of 274 patients and the validation cohort of 323 patients, for a total of 597 patients. An optimal NLR cutoff ≥ 4 was determined using receiver operating characteristic analysis. RESULTS: In multivariate models, NLR ≥ 4 was independently associated with lower odds for complete response to chemoimmunotherapy in the learning (odds ratio, 0.46; P = .006) and the validation cohort (odds ratio, 0.49; P = .01), and independently associated with worse survival in the learning (hazard ratio, 1.55; P = .04) and the validation cohort (hazard ratio, 1.80; P = .003). CONCLUSIONS: The adverse prognostic value of NLR ≥ 4 was independent of the International Prognostic Index and the National Comprehensive Cancer Network-International Prognostic Index score. Based on the results of this multi-institutional study, NLR ≥ 4 emerges as an adverse prognostic factor in Latin American patients with DLBCL treated with chemoimmunotherapy.
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Linfócitos/metabolismo , Linfoma Difuso de Grandes Células B/sangue , Neutrófilos/metabolismo , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
Introducción: La Enfermedad de Gaucher (EG) es un trastorno genético autosómico recesivo, causado por la deficiencia de la enzima B-Glucocerebrosidasa acida (GBA). En Colombia se ha estimado una prevalencia de 1:266.441 habitantes. Sin embargo, el país no cuenta con datos exactos sobre la incidencia, prevalencia y carga poblacional de esta enfermedad. Objetivo: Con el objetivo de caracterizar molecularmente las variantes encontradas en el gen GBA presentes en pacientes del Suroccidente Colombiano con enfermedad de Gaucher. Materiales y métodos: Se incluyeron 19 pacientes en el estudio, 57,8% de género masculino, con intérvalo de edad entre 4 y 71 años, diagnosticados clínica y enzimáticamente con EG. Se realizó un análisis molecular del gen GBA y posteriormente se buscaron las variantes en diferentes bases de datos poblacionales y clínicas; además se realizó análisis bioinformático para evaluar el posible impacto de las variantes de interés en la estructura y funcionalidad de la proteína. Resultados: Se encontraron 14/19 pacientes homocigotos; 4/19 heterocigotos compuestos y 1/19 heterocigotos). Se reportó la presencia de 7 variantes que codifican para 8 genotipos diferentes. El genotipo más frecuente es p.Asn409Ser/p.Asn409Ser (36%). De las 7 variantes encontradas, se reportó que específicamente p. Asn409Ser (10/23 alelos) y p.Leu483Pro (3/23 alelos) y p.Lys237Glu (3/23 alelos), están presentes en el 69,5% de los alelos. Todas las variantes presentaron una significancia clínica patogénica. Conclusiones: Este trabajo contribuye al establecimiento de las bases moleculares de la EG en los pacientes del Suroccidente Colombiano, permitiendo realizar una correlación genotipo-endotipo-fenotipo. Así mismo, se determina que los algoritmos de diagnóstico que incluyen análisis molecular y herramientas predictivas bioinformáticas permiten mejorar el diagnóstico, el tratamiento y el pronóstico de los pacientes afectados por EG, generando un impacto positivo en el seguimiento de los afectados, de la mano de una correcta consejería genética y estudios de portadores.
Introduction:Gaucher's disease (EG) is an autosomal recessive genetic disorder, caused by a deficiency of the acid B-Glucocerebrosidase (GBA) enzyme. In Colombia, a prevalence of 1: 266.441 inhabitants have been estimated. However, the country does not have exact data on the incidence, prevalence and population burden of this disease. Objective: molecularly characterize the variants found in the GBA gene present in patients from the Southwest of Colombia with Gaucher disease. Material and methods: 19 patients were included in the study, 57,8% male, with an age range between 4 and 71 years, clinically and enzymatically diagnosed with GD. A molecular analysis of the GBA gene was performed and the variants were subsequently searched in different population and clinical databases; In addition, a bioinformatic analysis was performed to evaluate the possible impact of the variants of interest on the structure and functionality of the protein. Results: 14/19 homozygous patients were found; 4/19 compound heterozygotes and 1/19 heterozygotes). The presence of 7 variants coding for 8 different genotypes was reported. The most frequent genotype was p.Asn409Ser/p.Asn409Ser (36%). Of the 7 variants found, it was reported that specifically p. Asn409Ser (10/23 alleles) and p.Leu483Pro (3/23 alleles) and p.Lys237Glu (3/23 alleles), are present in 69,5% of the alleles. All the variants presented a pathogenic clinical significance. Conclusion: This work contributes to the establishment of the molecular bases of GD in patients from the Southwest of Colombia, allowing a genotype-endotype-phenotype correlation to be carried out. Likewise, it is determined that diagnostic algorithms that include molecular analysis and bioinformatic predictive tools allow improving the diagnosis, treatment and prognosis of patients affected by GD, generating a positive impact on the follow-up of those affected, hand in hand with correct genetic counseling and carrier studies.