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2.
Rev. méd. Chile ; 151(3)mar. 2023.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1530266

RESUMEN

Natural killer/T cell lymphomas chiefly involving the midline facial structures including the nasal cavity or nasopharyns are a relatively rare type of non-Hodgkin's lymphoma. Apart from the upper respiratory tract, the disease occasionally presents in certain extranodal sites, such as the central nervous system, skin, gastrointestinal tract, or testes. We report a case of natural killer NK/T cell lymphoma as a testicular tumor in a 36-year-old man with a history of progressive swelling of his right testicle. Histologically, the testicular mass showed a diffuse infiltrate of medium-sized and atypical large lymphoid cells with angiocentric infiltration and areas of coagulative necrosis. Immunohistochemical studies demonstrated tumor cells staining positively with CD3, TIA-1, and Granzyme B. The Epstein-Barr virus genoma was detected by in situ hybridization. There were no abnormal findings in the nasal and nasopharyngeal regions. Classified as stage IEA, the patient received involved-field irradiation to contralateral testis (45 Gy), followed by systemic chemotherapy with a combination regimen ofL-asparaginase, methotrexate and dexamethasone. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

3.
Rev Med Chil ; 151(3): 381-386, 2023 Mar.
Artículo en Español | MEDLINE | ID: mdl-38293884

RESUMEN

Natural killer/T cell lymphomas chiefly involving the midline facial structures including the nasal cavity or nasopharyns are a relatively rare type of non-Hodgkin's lymphoma. Apart from the upper respiratory tract, the disease occasionally presents in certain extranodal sites, such as the central nervous system, skin, gastrointestinal tract, or testes. We report a case of natural killer NK/T cell lymphoma as a testicular tumor in a 36-year-old man with a history of progressive swelling of his right testicle. Histologically, the testicular mass showed a diffuse infiltrate of medium-sized and atypical large lymphoid cells with angiocentric infiltration and areas of coagulative necrosis. Immunohistochemical studies demonstrated tumor cells staining positively with CD3, TIA-1, and Granzyme B. The Epstein-Barr virus genoma was detected by in situ hybridization. There were no abnormal findings in the nasal and nasopharyngeal regions. Classified as stage IEA, the patient received involved-field irradiation to contralateral testis (45 Gy), followed by systemic chemotherapy with a combination regimen ofL-asparaginase, methotrexate and dexamethasone. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma de Células T , Masculino , Humanos , Adulto , Testículo/patología , Herpesvirus Humano 4 , Metotrexato , Linfoma de Células T/patología , Linfoma de Células T/terapia
4.
Cancers (Basel) ; 14(19)2022 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-36230571

RESUMEN

(1) Background: The epigenetic regulator EZH2 is a subunit of the polycomb repressive complex 2 (PRC2), and methylates H3K27, resulting in transcriptional silencing. It has a critical role in lymphocyte differentiation within the lymph node. Therefore, mutations at this level are implicated in lymphomagenesis. In fact, the mutation at the Y641 amino acid in the EZH2 gene is mutated in up to 40% of B-cell lymphomas. (2) Methods: We compared the presence of exon 16 EZH2 mutations in tumor samples and ctDNA in a prospective trial. These mutations were determined by Sanger sequencing and ddPCR. (3) Results: One hundred and thirty-eight cases were included. Ninety-eight were germinal center, and twenty had EZH2 mutations. Mean follow-up (IQR 25-75) was 23 (7-42) months. The tumor samples were considered the standard of reference. Considering the results of the mutation in ctDNA by Sanger sequencing, the sensibility (Se) and specificity (Sp) were 52% and 99%, respectively. After adding the droplet digital PCR (ddPCR) analysis, the Se and Sp increased to 95% and 100%, respectively. After bivariate analysis, only the presence of double-hit lymphoma (p = 0.04) or EZH2 mutations were associated with relapse. The median Progression free survival (PFS) (95% interval confidence) was 27.7 (95% IC: 14-40) vs. 44.1 (95% IC: 40-47.6) months for the mutated vs. wild-type (wt) patients. (4) Conclusions: The ctDNA is useful for analyzing EZH2 mutations, which have an impact on PFS.

5.
Front Cell Dev Biol ; 9: 695723, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34957087

RESUMEN

The p53 roles have been largely described; among them, cell proliferation and apoptosis control are some of the best studied and understood. Interestingly, the mutations on the six hotspot sites within the region that encodes the DNA-binding domain of p53 give rise to other very different variants. The particular behavior of these variants led to consider p53 mutants as separate oncogene entities; that is, they do not retain wild type functions but acquire new ones, namely Gain-of-function p53 mutants. Furthermore, recent studies have revealed how p53 mutants regulate gene expression and exert oncogenic effects by unbalancing specific microRNAs (miRNAs) levels that provoke epithelial-mesenchymal transition, chemoresistance, and cell survival, among others. In this review, we discuss recent evidence of the crosstalk between miRNAs and mutants of p53, as well as the consequent cellular processes dysregulated.

6.
Rev. méd. Chile ; 149(8): 1231-1235, ago. 2021. ilus
Artículo en Inglés | LILACS | ID: biblio-1389573

RESUMEN

ABSTRACT Primary myocardial involvement of Diffuse Large B-Cell lymphoma is extremely rare, accounting for 0.5 % of all lymphomas. We report a 65-year-old male, presenting with an acute cardiac tamponade, which was drained. A pericardial window with myocardial biopsy was carried out, disclosing a diffuse large B cell lymphoma. He received 6 cycles of rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), without response. Finally, a palliative chemotherapy with gemcitabine plus oxaliplatin was prescribed.


El linfoma difuso de células grandes B, primario del miocardio es muy raro. Presentamos un varón de 65 años que se presentó con un taponamiento cardíaco agudo que fue drenado. La biopsia miocárdica un mostró linfoma difuso de células grandes B, primario de miocardio. El paciente recibió 6 ciclos de quimioterapia con rituximab, ciclofosfamida, vincristina y prednisona sin respuesta. Finalmente se optó por una quimioterapia paliativa con gemcitabina y oxaliplatino.


Asunto(s)
Humanos , Masculino , Anciano , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Vincristina/uso terapéutico , Prednisona/uso terapéutico , Ciclofosfamida/uso terapéutico , Rituximab/uso terapéutico
7.
JCO Glob Oncol ; 7: 1151-1166, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34270330

RESUMEN

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.


Asunto(s)
Leucemia-Linfoma de Células T del Adulto , Linfoma , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Argentina , Chile , Colombia , Humanos , América Latina/epidemiología , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/epidemiología , Persona de Mediana Edad , Perú/epidemiología
8.
Ther Adv Hematol ; 12: 2040620721989579, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33796235

RESUMEN

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkin lymphoma worldwide. The current standard of care is chemoimmunotherapy with an R-CHOP regimen. We aim to review the role of this regimen after two decades of being the standard of care. METHODS: A comprehensive literature review of DLBCL, including the epidemiology, trials defining R-CHOP as the standard of care, as well as dose intensification and dose reduction schemes. Additionally, we briefly review the development of rituximab biosimilars and the addition of targeted drugs to R-CHOP in clinical trials. DISCUSSION: R-CHOP cures approximately 70% of DLBCL patients. Dose-dense regimens do not show a benefit in response and increase toxicity. Dose reduction, particularly in elderly patients or with comorbidities, may be a treatment option. DLBCL constitutes a group of diseases that activate different biological pathways. Matching specific treatments to a defined genetic alteration is under development. Rituximab biosimilars have become available to a broader population, particularly in developing countries, where access to treatment is limited because of economic resources. CONCLUSION: DLBCL landscape is heterogeneous. R-CHOP immunochemotherapy has been a standard of care for two decades and cures approximately 70% of cases. Molecular characterization of patients is evolving and may have critical therapeutic implications.

9.
Rev Med Chil ; 149(8): 1231-1235, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35319711

RESUMEN

Primary myocardial involvement of Diffuse Large B-Cell lymphoma is extremely rare, accounting for 0.5 % of all lymphomas. We report a 65-year-old male, presenting with an acute cardiac tamponade, which was drained. A pericardial window with myocardial biopsy was carried out, disclosing a diffuse large B cell lymphoma. He received 6 cycles of rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), without response. Finally, a palliative chemotherapy with gemcitabine plus oxaliplatin was prescribed.


Asunto(s)
Linfoma de Células B Grandes Difuso , Anciano , Ciclofosfamida/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéutico
10.
Rev. colomb. cancerol ; 24(supl.1): 192-226, oct.-dic. 2020. tab, graf
Artículo en Español | LILACS | ID: biblio-1251509

RESUMEN

Resumen En diciembre de 2019 se detectó por primera vez en China la existencia del SARS-CoV2, causante de la enfermedad COVID-19. El virus rápidamente se propagó por Europa y Asia, tardándose un par de meses antes de llegar a América Latina. Se ha demostrado que los pacientes que desarrollan una enfermedad severa y que tienen mayor riesgo de mortalidad por COVID-19 son aquellos con edades avanzadas y que presentan por lo menos una enfermedad crónica, incluyendo el cáncer. Debido a lo anterior, surgen muchas dudas en el grupo de profesionales encargados de brindar tratamiento a pacientes con cáncer durante la pandemia, pues se debe equilibrar el riesgo-beneficio de proveer tratamiento a pacientes que se encuentran de base con un riesgo incrementado para tener manifestaciones severas por COVID-19. En este consenso planteamos recomendaciones para los profesionales en hematología que brindan tratamiento a pacientes que padecen de algún tipo de linfoma, con el fin de aclarar el panorama clínico durante la pandemia.


Abstract The existence of SARS-CoV2, the cause of COVID 19 disease, was detected for the first time in China in December 2019. The virus quickly spread across Europe and Asia, taking a couple months to reach Latin America. It has been shown that elderly patients and those with chronic diseases, including cancer, have a higher risk of mortality from COVID-19. Consequently, many doubts arise in the group of health professionals responsible for treating patients with cancer during the pandemic, as they must balance the risk-benefit of delivering treatment to patients with an increased risk for severe manifestations resulting from COVID-19. In this consensus we propose recommendations for hematology professionals who provide treatment to patients suffering from some type of lymphoma, with the aim of clarifying the clinical picture during the pandemic.


Asunto(s)
Humanos , Síndrome Respiratorio Agudo Grave , COVID-19 , Linfoma , Consenso , Pandemias
11.
Rev. méd. Chile ; 148(9)sept. 2020.
Artículo en Inglés | LILACS | ID: biblio-1389324

RESUMEN

ABSTRACT Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.


El síndrome mielodisplásico con deleción del cromosoma 5q (síndrome 5q) tiene un pronóstico favorable y riesgo bajo de transformación a leucemia aguda en pacientes que son tratados con lenalidomida (tratamiento estándar). El uso Azactidina tiene respuestas completas incluso como segunda línea de tratamiento en pacientes con evolución clonal. Presentamos una mujer de 71 años, sin exposición a mielotóxicos que debutó con un síndrome anémico. Se realizó biopsia de medula ósea que mostró celularidad del 50% y en el análisis citogenético se detectó una deleción del cromosoma 5 en 22% de las metafases analizadas, lo que llevó al diagnóstico de Síndrome 5q- de riesgo bajo de acuerdo con el puntaje IPSS-R (Revised International Prognostic Scoring System). Ya que no se pudo costear lenalidomida, se trató con talidomida (100 mg/día). Permaneció tres años sin requerir soporte transfusional. Posteriormente, presentó pancitopenia y en el nuevo aspirado de médula ósea se observó displasia de la serie roja y megacariocitos, con cariotipo complejo y peor pronóstico (IPSS-R 5 puntos). Se trató con 12 ciclos de azacitidina con lo que logró respuesta completa. Recayó 12 meses después y continuó manejo de soporte por un año. Finalmente falleció debido a un accidente vascular cerebral.


Asunto(s)
Anciano , Femenino , Humanos , Talidomida , Síndromes Mielodisplásicos , Deleción Cromosómica , Inhibidores de la Angiogénesis , Anemia Macrocítica , Talidomida/uso terapéutico , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/tratamiento farmacológico , Cromosomas Humanos Par 5/genética , Resultado del Tratamiento , Inhibidores de la Angiogénesis/uso terapéutico , Lenalidomida , Anemia Macrocítica/genética , Anemia Macrocítica/tratamiento farmacológico
12.
Clin Lymphoma Myeloma Leuk ; 20(10): 637-646, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32513598

RESUMEN

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.


Asunto(s)
Linfocitos/metabolismo , Linfoma de Células B Grandes Difuso/sangre , Neutrófilos/metabolismo , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia
13.
Rev Med Chil ; 148(9): 1357-1361, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33399713

RESUMEN

Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.


Asunto(s)
Anemia Macrocítica , Inhibidores de la Angiogénesis , Deleción Cromosómica , Síndromes Mielodisplásicos , Talidomida , Anciano , Anemia Macrocítica/tratamiento farmacológico , Anemia Macrocítica/genética , Inhibidores de la Angiogénesis/uso terapéutico , Cromosomas Humanos Par 5/genética , Femenino , Humanos , Lenalidomida , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Talidomida/uso terapéutico , Resultado del Tratamiento
14.
Rev Invest Clin ; 71(5): 349-358, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31599881

RESUMEN

BACKGROUND: The outcome of patients with primary extranodal diffuse large B-cell lymphoma (PE-DLBCL) varies according to the primary site involved. Primary gastrointestinal, breast, bone, craniofacial, and testicular DLBCL are rare extranodal manifestations of DLBCL. OBJECTIVE: The objective of the study was to describe the clinical course of patients with PE-DLBCL disease in a referral cancer center. RESULTS: From 637 patients, 51 (8.77%) were considered as having PE-DLBCL (25 gastrointestinal, 12 craniofacial, 6 breast, 5 bone, and 3 with primary testicular DLBCL). Complete remission was higher in all PE-DLBCL sites (100% in testicular, 92.6% craniofacial, 83.3% breast, 80% bone, and 80% gastrointestinal) compared with 73.3% in nodal DLBCL. Although 2 cases with breast PE-DLBC relapsed, they achieved a complete response with chemotherapy. The overall survival at 5 years was 100%, 80%, 78%, 58%, 58%, and 62% for patients with primary breast, primary bone, gastrointestinal, primary craniofacial, primary testicular, and nodal DLBCL, respectively. CONCLUSIONS: PE-DLBCLs constitute rare, primary sites of lymphoproliferative disorders in most cases, with localized disease and good prognosis. They require a combined chemoimmunotherapy with radiotherapy in most cases to improve local and systemic disease.


Asunto(s)
Antineoplásicos/administración & dosificación , Inmunoterapia/métodos , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Terapia Combinada , Femenino , Humanos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
15.
Rev. invest. clín ; 71(5): 349-358, Sep.-Oct. 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1289705

RESUMEN

Background The outcome of patients with primary extranodal diffuse large B-cell lymphoma (PE-DLBCL) varies according to the primary site involved. Primary gastrointestinal, breast, bone, craniofacial, and testicular DLBCL are rare extranodal manifestations of DLBCL. Objective The objective of the study was to describe the clinical course of patients with PE-DLBCL disease in a referral cancer center. Results From 637 patients, 51 (8.77%) were considered as having PE-DLBCL (25 gastrointestinal, 12 craniofacial, 6 breast, 5 bone, and 3 with primary testicular DLBCL). Complete remission was higher in all PE-DLBCL sites (100% in testicular, 92.6% craniofacial, 83.3% breast, 80% bone, and 80% gastrointestinal) compared with 73.3% in nodal DLBCL. Although 2 cases with breast PE-DLBC relapsed, they achieved a complete response with chemotherapy. The overall survival at 5 years was 100%, 80%, 78%, 58%, 58%, and 62% for patients with primary breast, primary bone, gastrointestinal, primary craniofacial, primary testicular, and nodal DLBCL, respectively. Conclusions PE-DLBCLs constitute rare, primary sites of lymphoproliferative disorders in most cases, with localized disease and good prognosis. They require a combined chemoimmunotherapy with radiotherapy in most cases to improve local and systemic disease.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Linfoma de Células B Grandes Difuso/patología , Inmunoterapia/métodos , Ganglios Linfáticos/patología , Antineoplásicos/administración & dosificación , Pronóstico , Tasa de Supervivencia , Estudios Retrospectivos , Estudios de Cohortes , Linfoma de Células B Grandes Difuso/terapia , Resultado del Tratamiento , Terapia Combinada
16.
Rev. lab. clín ; 12(3): 133-136, jul.-sept. 2019. ilus, tab, graf
Artículo en Español | IBECS | ID: ibc-187167

RESUMEN

Systemic Lupus Erythematosus (SLE) as an autoimmune disorder, is characterized by a profound B cell activation, however, the association of this disease with a monoclonal gammopathy has been infrequently reported, while hypercalcemia is associated with Hypercalcemia-Lymphadenopathy Syndrome (HL-SLE). We report the case of a 45-year-old man, with anemia, hypoalbuminemia, hypergammaglobulinemia, hypercalcemia, and bone marrow infiltrated with plasma cells. He was diagnosed as Monoclonal Gammopathy of Undetermined Significance (MGUS), one year later he attended with erythematous macules on both arms, at this time the electrophoresis reported a polyclonal hypergammaglobulinemia. Immunologic panel reported ANA 1:2560, mitochondrial ANA 1:80, anti-double-stranded DNA IgG 15.3 and hipocomplementemia. We confirmed SLE and treatment was initiated. In our patient we ruled out MGUS, γHCD (γ-heavy-chain disease) and hypercalcemia related to HL-SLE. To our knowledge, the findings of monoclonal gammopathy and hypercalcemia as the onset of SLE have never been reported and the role of clinical laboratory was very important in the approach to establish a definitive diagnosis


El lupus eritematoso sistémico (LES) es un padecimiento autoinmune, caracterizado por la activación de las células B. Se ha reportado ocasionalmente su asociación con la gammapatía monoclonal. Reportamos el caso de un varón de 45 años con anemia, hipoalbuminemia, hipergammaglobulinemia, hipercalcemia e infiltración de médula ósea con células plasmáticas. Se diagnosticó de gammapatía monoclonal de significado incierto. Posteriormente presentó máculas en brazos, con hipergammaglobulinemia policlonal y serología con ANA 1:2.560, ANA mitocondriales 1:80, IgG 15,3 e hipocomplementemia que establecieron el diagnóstico de LES. La presencia de hipercalcemia y gammapatía monoclonal en asociación con LES no se había reportado con anterioridad


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Paraproteinemias/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Hipoalbuminemia/diagnóstico , Hipergammaglobulinemia/diagnóstico , Hipercalcemia/diagnóstico , Células Plasmáticas/patología
17.
Leuk Lymphoma ; 60(14): 3375-3385, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31272251

RESUMEN

This multicenter, double-blind, randomized study compared the efficacy, pharmacokinetics (PKs)/pharmacodynamics (PDs), safety and immunogenicity profile of RTXM83 vs. reference rituximab (R-rituximab), both with CHOP, as first-line treatment of diffuse large B-cell lymphoma (DLBCL). A total of 272 patients <65 years of age, with good prognosis (136 per arm) were randomized (1:1) to receive six cycles of either RTXM83 or R-rituximab. The primary efficacy endpoint was achieved (overall response rate of 83.6% for RTXM83 and 82.9% for R-rituximab) with a difference 0.7% between arms (95%CI: [-8.77% to 10.17%]) fulfilling the predefined non-inferiority margin (-13%). Similar number of patients reported at least one adverse event (AE) (131 per arm) or one serious AE (47 with RTXM83 and 45 with R-rituximab). Anti-drug antibody development was comparable between the arms. PK/PD secondary endpoint results support similarity between the compounds. RTXM83 exhibits non-inferior efficacy and similar safety/immunogenicity to R-rituximab, being an accessible alternative for the treatment of patients with previously untreated DLBCL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Biosimilares Farmacéuticos/administración & dosificación , Ciclofosfamida/administración & dosificación , Método Doble Ciego , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Rituximab/administración & dosificación , Tasa de Supervivencia , Vincristina/administración & dosificación , Adulto Joven
18.
J Neurooncol ; 140(3): 569-574, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30120662

RESUMEN

INTRODUCTION: Cerebrovascular disease (CVD) and cancer are among the most common causes of mortality worldwide, preceded only by ischemic heart disease (IHD). Thrombocytopenia was shown to be associated with poor outcomes in IHD and CVD in the general population. This study aimed to assess the relationship of thrombocytopenia with poor outcomes in cancer patients with CVD. MATERIALS AND METHODS: Data on patients with concomitant CVD and cancer who were initially treated at a cancer referral center between January 2010 and December 2017 were included. Thrombocytopenia was defined as a platelet count < 150,000/mm3 during the first 24 h of CVD symptom onset. The IRB (CI/837/17) approved the review of clinical records. RESULTS: Among 268 cancer patients with CVD included in the study, 210 met the inclusion criteria. Median overall survival of the entire cohort was 7.2 months, which was significantly shorter in males (p = 0.029) and patients with hematologic tumors (p = 0.009), hemorrhagic CVD (p < 0.001), altered mental status (p < 0.001), and thrombocytopenia (p < 0.001). Multiple regression logistic analysis revealed that thrombocytopenia (risk ratio [RR] 1.6, 95% confidence interval [CI] 1.1-2.4) and altered mental status (RR 2.7, 95% CI 1.9-4.0) remained statistically significant risk factors for mortality. CONCLUSION: In cancer patients with CVD, thrombocytopenia at the time of CVD diagnosis and altered mental status during initial clinical evaluation were associated with higher mortality, which should be confirmed in future studies.


Asunto(s)
Trastornos Cerebrovasculares/complicaciones , Neoplasias/sangre , Neoplasias/diagnóstico , Accidente Cerebrovascular/complicaciones , Trombocitopenia/complicaciones , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/epidemiología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Oportunidad Relativa , Recuento de Plaquetas , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/epidemiología , Trombocitopenia/epidemiología
19.
Oncol Lett ; 16(2): 1411-1418, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30008818

RESUMEN

An early discrimination of survival probability is required for patients with diffuse large B cell lymphoma (DLBCL), which may identify patients that require other treatment options, for example clinical trials. To the best of our knowledge, the impact of interim evaluation with 18fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has not yet been determined in this type of neoplasia. The aim of the present study was to determine the role of changes in metabolic tumor volume (MTV) between baseline and interim 18F-FDG PET/CT scans, following three courses of chemotherapy in order to predict complete response (CR) and overall survival (OS) in patients with DLBCL. Patients with previously untreated DLBCL who had received the standard 6-8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone were included in the present study. A predictive model was constructed using changes in MTV and other clinical factors including age, gender, East Cooperative Oncology Group (ECOG) status, clinical stage, B symptoms, the presence of bulky disease and elevated lactate dehydrogenase levels, and data were analyzed using logistic regression analysis. In total, 50 patients with DLBCL were included in the present study. The majority of patients presented with stage III/IV disease (64%), B symptoms (72%) and bulky disease (58%). According to the International Prognostic Index score, 44% of patients were in the intermediate-high or high-risk categories for risk of relapse, and therefore considered to have poor prognosis. In total, ≥94% of patients achieving a decrease in total MTV had a 2-year OS rate of 95%, compared with the 58% OS rate of those with a suboptimal response. A multivariate model, including a change in MTV (a decrease of ≥94%), the ECOG performance status ≥2, a change in leukocyte counts and age, was used to predict CR. This model was used to define two groups according to the predicted probability of recurrence (cutoff, 0.69). The 2-year survival rates of the two groups were 95 and 59%, respectively. Analysis of changes in MTV in the interim 18F-FDG PET/CT revealed significant prognostic value for the prediction of CR and OS in patients with DLBCL.

20.
Rev Invest Clin ; 70(1): 46-52, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29513304

RESUMEN

BACKGROUND: Available prognosis scores for patients with diffuse large B-cell lymphoma (DLBCL) included a limited number of patients ≥ 65 years of age, and most of them did not include comorbidities. Here, we propose a prognostic score for overall survival (OS) for this group of patients. MATERIALS AND METHODS: Patients ≥ 65 years with DLBCL treated at a single national reference center were included. Clinical features including comorbidities and biochemical parameters were analyzed. RESULTS: We included 141 patients. Response rate in the whole group was 77%. Based on multivariate analysis, the presence of the European Cooperative Oncology Group (ECOG) > 2, elevated levels of beta-2 microglobulin, bulky disease, and anemia (hemoglobin < 10 g/dL) had a significant effect on OS. These parameters were considered when computing the prognostic score, which identified three groups with differential survival: Low, intermediate, and high risk of death, with a probability of survival at 60 months of 80.05%, 55.5%, and 29.84%, respectively. DISCUSSION: This score may select patients to optimize treatment. The presence of high levels of beta-2 microglobulin, bulky disease, and hemoglobin < 10 g/dL, and ECOG > 2 was associated with poor OS in elderly patients with DLBCL.


Asunto(s)
Anemia/epidemiología , Linfoma de Células B Grandes Difuso/patología , Microglobulina beta-2/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
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