RESUMO
Importance: Hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives: To analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants: This case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures: Primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results: Among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance: These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.
Assuntos
Apolipoproteína A-V/genética , Apolipoproteína C-III/genética , Bexaroteno/uso terapêutico , Hipertrigliceridemia/etiologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Apolipoproteína A-V/metabolismo , Apolipoproteína C-III/metabolismo , DNA/genética , Feminino , Seguimentos , Genótipo , Humanos , Hipertrigliceridemia/genética , Hipertrigliceridemia/metabolismo , Linfoma Cutâneo de Células T/complicações , Linfoma Cutâneo de Células T/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
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Assuntos
Masculino , Pessoa de Meia-Idade , Humanos , Eritema/diagnóstico , Eritema/terapia , Caquexia/diagnóstico , Biópsia , Tomografia Computadorizada de Emissão/métodos , Carcinoma/diagnóstico , Colonoscopia/métodos , Imuno-Histoquímica/métodos , Diagnóstico Diferencial , Terapia Combinada , Umbigo/patologia , Caquexia/complicações , Carcinoma/complicações , Eritema/complicações , Umbigo/cirurgia , Umbigo , Hiperuricemia/complicações , Neoplasias Abdominais/diagnóstico , Neoplasias Abdominais/terapiaRESUMO
Merkel cell carcinoma (MCC) is an infrequent neuroendocrine tumor of the skin with a high potential for local recurrence, lymphatic dissemination and distant dissemination. We present a case of MCC in a male patient with chronic lymphocytic leukemia (CLL). The immunosuppression induced by the leukemia or by the chemotherapy could play a pathogenic role in the association of these diseases. Positron emission tomography (PET) was a useful staging technique in this patient, and made the differential diagnosis of the lymph node involvement from MMC and CLL possible.
Assuntos
Carcinoma de Célula de Merkel/patologia , Leucemia Linfocítica Crônica de Células B , Segunda Neoplasia Primária/patologia , Neoplasias Cutâneas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Célula de Merkel/diagnóstico por imagem , Carcinoma de Célula de Merkel/radioterapia , Carcinoma de Célula de Merkel/secundário , Carcinoma de Célula de Merkel/cirurgia , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Humanos , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/imunologia , Excisão de Linfonodo , Metástase Linfática/radioterapia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico por imagem , Segunda Neoplasia Primária/radioterapia , Segunda Neoplasia Primária/cirurgia , Tomografia por Emissão de Pósitrons , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Radioterapia Adjuvante , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
El carcinoma de células de Merkel (CCM) es un tumor neuroendocrino cutáneo infrecuente con un elevado potencial de recurrencias locales, diseminación linfática y diseminación a distancia. Presentamos un caso de CCM en un paciente con leucemia linfática crónica (LLC). La inmunosupresión inducida por la leucemia o por la quimioterapia podría desempeñar un papel patogénico en la asociación de estas enfermedades. La tomografía por emisión de positrones (PET) es una técnica de estadiaje útil en este paciente, y permite el diagnóstico diferencial de la afectación ganglionar por CCM y LLC
Merkel cell carcinoma (MCC) is an infrequent neuroendocrine tumor of the skin with a high potential for local recurrence, lymphatic dissemination and distant dissemination. We present a case of MCC in a male patient with chronic lymphocytic leukemia (CLL). The immunosuppression induced by the leukemia or by the chemotherapy could play a pathogenic role in the association of these diseases. Positron emission tomography (PET) was a useful staging technique in this patient, and made the differential diagnosis of the lymph node involvement from MMC and CLL possible
