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.
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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/terapiaRESUMEN
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.
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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 terapéuticoRESUMEN
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.
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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 TratamientoRESUMEN
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.
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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 TratamientoRESUMEN
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.
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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/epidemiologíaRESUMEN
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.
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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 SupervivenciaRESUMEN
The hypomethylating agents azacytidine and decitabine are unaffordable for many patients with MDS. The combination of the DNA methyltransferase inhibitor hydralazine and the histone deacetylase inhibitor valproate has shown preliminary efficacy in MDS. The aim of this study is to evaluate the clinical efficacy and safety of hydralazine/valproate in a case series of MDS patients treated in a compassionate manner. Hydralazine was dosed according to the acetylation genotype of patients (slow acetylators 83 mg daily; fast acetylators 182 mg daily), and valproate was dosed at 30 mg/kg/day. Both drugs were given daily until disease progression. Response and toxicity were evaluated with the International Working Group criteria and CTCAE, version 4, respectively. Survival parameters were estimated with the Kaplan-Meier method. From 2009 to 2012, 14 patients were treated. The median age ± SD was 55.2 ± 19.52 (range 23-87) years. According to the IPSS, cases were graded as intermediate-1 (n = 8/14; 57.2%) or intermediate-2 (n = 6/14; 42.8%). Responses were as follows: five (35.7%) complete response, one (7.1%) partial response, and two (14.28%) became transfusion independent. The mean duration of response ± SD was 60 ± 35.28 months (range 5-94). Three patients progressed to AML. At a median follow-up of 57 months (range 1-106), the median OS was 27 months. At that point, five patients remained on the treatment, one with partial response and four with complete response. The median OS was not reached in the eight patients who saw a clinical benefit from the treatment, in comparison to an OS of 7 months in the six patients who had no treatment. The combination of hydralazine and valproate is safe and effective in MDS, and its further testing is highly desirable.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ensayos de Uso Compasivo/métodos , Epigénesis Genética/efectos de los fármacos , Hidralazina/administración & dosificación , Síndromes Mielodisplásicos/tratamiento farmacológico , Ácido Valproico/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Ensayos de Uso Compasivo/mortalidad , Epigénesis Genética/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Adulto JovenRESUMEN
Blastic plasmacytoid dendritic cell neoplasm is a rare hematological malignancy derived from immature plasmacytoid dendritic cells. The tumor cells have an immature blastic appearance, and diagnosis is based on the expression of CD4, CD56 y CD123 in the absence of other lymphoid, natural killer, or myeloid antigens. The majority of affected individuals are older people with a mean age of 66 years. Male to female ratio is approximately 3:1. Common presentation includes cutaneous lesions followed by tumor dissemination. Treatment with conventional chemotherapy is ineffective and allogeneic hematopoietic stem cell transplantation is required to achieve remission. We report three male patients, aged 23, 27 and 51 years with the disease. All had multiple, infiltrated pink plaques and nodules on the skin of their face, neck and thorax, measuring 1 to 12 cm in diameter. All tumors were histologically characterized by a monotonous proliferation of medium size cells with blastic features. Tumor cells were positive for CD123, CD56, CD4 and CD7 in all cases. After a mean of follow-up of 14.6 months, one patient died of the disease, one patient is alive and the disease relapsed after 17 months of remission and one patient is alive with no evidence of the disease.
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Células Dendríticas/patología , Neoplasias Hematológicas/patología , Adulto , Biopsia , Médula Ósea/patología , Resultado Fatal , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Piel/patología , Adulto JovenRESUMEN
We report a 73-year-old female patient with Castleman's disease coexistent with large B cell type non-Hodgkin's lymphoma in a right axillary lymphadenopathy. An excisional biopsy was performed: microscopically, the lymph node revealed the presence of numerous plasma cells and small lymphoid cells characteristic of Castleman's disease. An analysis of another portion of the specimen revealed lymphoid cells with large abnormal nuclei gathered locally that were CDD 79+, CD 38+ and MUM-1+ as well as positive for Kaposi sarcoma-associated herpesvirus and negative for Epstein Barr virus encoded RNA-1 (EBER).
Asunto(s)
Enfermedad de Castleman/complicaciones , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/complicaciones , Anciano , Enfermedad de Castleman/patología , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patologíaRESUMEN
BACKGROUND: Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter (hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug. METHODS: AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival. RESULTS: Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival. CONCLUSIONS: These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients.
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Antimetabolitos Antineoplásicos/uso terapéutico , Citarabina/uso terapéutico , Desoxicitidina Quinasa/genética , Tranportador Equilibrativo 1 de Nucleósido/genética , Regulación Leucémica de la Expresión Génica , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Anciano , Desoxicitidina Quinasa/metabolismo , Doxorrubicina/uso terapéutico , Tranportador Equilibrativo 1 de Nucleósido/metabolismo , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Reacción en Cadena en Tiempo Real de la Polimerasa , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Lymphoproliferative disorders have increased in last decades. Immunohistochemistry analysis is required to categorize them in different clinical entities, as has been stablished by WHO. Advances in imaging have set the PET-CT as a standard staging procedure in most cases. Knowledge of the biology of these malignancies has allowed therapeutic advances with different approaches, including development of monoclonal antibodies, conjugated antibodies, immunomodulatory agents, as well as inhibition of specific pathways. Although new drugs are promising, the cost-benefit impact requires to be evaluated in pharmacoeconomic clinical trials.
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Linfoma/diagnóstico , Linfoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Diagnóstico por Imagen/tendencias , Manejo de la Enfermedad , Drogas en Investigación/uso terapéutico , Humanos , Inmunoterapia , Linfoma/epidemiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/terapia , Oncología Médica/tendencias , Terapia Molecular Dirigida , Terapias en InvestigaciónRESUMEN
BACKGROUND: Hyper-CVAD is the treatment for patients with acute lymphoblastic leukemia in our institution. OBJECTIVE: To evaluate the impact of single nucleotide polymorphisms at genes associated with methotrexate metabolism on survival. METHODS: The presence of the single nucleotide polymorphisms G80A at reduced folate carrier-1 gene and C677T in the methylenetetrahydrofolate reductase gene was determined by denaturing high performance liquid chromatography and validated by sequencing. Both single nucleotide polymorphisms were evaluated in 71 healthy donors and in an exploratory pilot trial with acute lymphoblastic leukemia patients to determine the influence of these single nucleotide polymorphisms on clinical outcome. Clinical characteristics, response, and outcome were registered. A Cox regression analysis was done to evaluate factors influencing response and overall survival. RESULTS: There were no differences in the frequency of single nucleotide polymorphisms between volunteers and acute lymphoblastic leukemia patients according to the Hardy-Weinberg test. Sensitivity and specificity were 72 and 91% for the G80A, and 64 and 75% for the C677T, respectively. The multivariate analysis showed that the T-immunophenotype and the presence of single nucleotide polymorphism G80A reduced folate carrier-1 were associated with a shorter relapse-free survival and overall survival. CONCLUSIONS: The presence of G80A single nucleotide polymorphism at reduced folate carrier-1 gene in acute lymphoblastic leukemia patients was associated with a poorer prognosis.
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Proteínas de Transporte de Membrana/genética , Metotrexato/administración & dosificación , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cromatografía Líquida de Alta Presión , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Metotrexato/metabolismo , México , Persona de Mediana Edad , Análisis Multivariante , Proyectos Piloto , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sensibilidad y Especificidad , Tasa de Supervivencia , Vincristina/administración & dosificación , Adulto JovenRESUMEN
The actual standard of care of diffuse large B-cell lymphoma (DLBCL) includes rituximab in combination with chemotherapy, with response rates up to 76%. However, this treatment may not be accessible to many patients, particularly in developing countries, where most of the treatment must be paid from the pocket of patients or their families. In México, since 2011 a federal program has fully covered this treatment of patients with DLBCL. At the Instituto Nacional de Cancerología (INCan) in Mexico City, 214 new cases with this disease were treated without cost with the standard of care in 20 months. The mean age at diagnosis was 56.7 ± 15.9 (22-91). This series of cases was compared with a retrospective analysis of cases with DLBCL attended at the INCan between 2006-2009. A total of 264 cases were retrospectively analyzed. No differences were found in demographic and clinical characteristics at time of diagnosis. However a clear positive impact was found in the group that received full treatment thanks to this new social coverage by this new social security program. The follow-up and completion of treatment was 99 %. In contrast; from 264 in the retrospective group (79%) were treated, but only 29 (10.9%) were able to receive an optimal treatment, including rituximab. These differences in treatments had a clearly impact on the response rate: 66.8 vs. 50.7% global response (full treatment vs. retrospective group, respectively). These results demonstrate the importance of social programs that may accessible standard treatment options in countries with limited resources.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Accesibilidad a los Servicios de Salud/economía , Linfoma de Células B Grandes Difuso/patología , Programas Nacionales de Salud , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/economía , Masculino , México , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: The pharmacological treatment of cancer has evolved from cytotoxic to molecular targeted therapy. The median survival gains of 124 drugs approved by the FDA from 2003 to 2021 is 2.8 months. Targeted therapy is based on the somatic mutation theory, which has some paradoxes and limitations. While efforts of targeted therapy must continue, we must study newer approaches that could advance therapy and affordability for patients. AREAS COVERED: This work briefly overviews how cancer therapy has evolved from cytotoxic chemotherapy to current molecular-targeted therapy. The limitations of the one-target, one-drug approach considering cancer as a robust system and the basis for multitargeting approach with polypharmacotherapy using repurposing drugs. EXPERT OPINION: Multitargeted polypharmacotherapy for cancer with repurposed drugs should be systematically investigated in preclinical and clinical studies. Remarkably, most of these proposed drugs already have a long history in the clinical setting, and their safety is known. In principle, the risk of their simultaneous administration should not be greater than that of a first-in-human phase I study as long as the protocol is developed with strict vigilance to detect early possible side effects from their potential interactions. Research on cancer therapy should go beyond the prevailing paradigm targeted therapy.
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Antineoplásicos , Reposicionamiento de Medicamentos , Terapia Molecular Dirigida , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Animales , Tasa de Supervivencia , Polifarmacología , Desarrollo de MedicamentosRESUMEN
Non-Hodgkin lymphoma comprises a heterogeneous group of haematological malignancies, classified according to their clinic, anatomic-pathological features and, lately, to their molecular biomarkers. Despite the therapeutic advances, nearly half of the patients will die because of this disease. The new diagnostic tools have been the cornerstone to design recent therapy targets, which must be included in the current treatment guidelines of this sort of neoplasms by means of clinical trials and evidence-based medicine. In the face of poor diagnoses devices in most of the Mexican hospitals, we recommend the present diagnose stratification, and treatment guidelines for non-Hodgkin lymphoma, based on evidence. They include the latest and most innovative therapeutic approaches, as well as specific recommendations for hospitals with limited framework and therapy resources.
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Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/terapia , Humanos , MéxicoRESUMEN
AIMS: The objectives of this report are, first, to describe the clinical behavior of cases of carcinoma metastatic to the uterine cervix treated at our institution in order to carry out a systematic review to establish the behavioral patterns of the most frequent metastases to the cervix and, second, to generate guidelines for their diagnosis and treatment. METHODS: At the National Institute of Cancer of Mexico (INCan), we performed a review of the clinical files with a diagnosis of malignant neoplasm metastatic to the uterine cervix between 1990 and 2009. For a systematic review, we conducted a PubMed search between the years 1970 and 2009 of case reports and series of cases of patients with metastatic gastric, breast, ovarian and colorectal cancer. We analyzed each report individually and extracted the patients' clinical data from our cases and reports, including the primary tumor, cervical metastases and survival rates. RESULTS: There were 10 cases of tumors metastatic to the uterine cervix. Metastasis was documented in one-half of the patients during follow up, with two of these cases having the cervix as the only site. We included the following reports in the systematic review: 13 reports of gastric-associated cancer, 30 related to breast cancer, nine with ovarian-associated cancer and 10 related to colorectal cancer. CONCLUSIONS: Metastatic cervical activity is an infrequent event. The prognosis of survival is poor in the presence of gastric or ovarian cancer and cervical metastases.
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Adenocarcinoma/secundario , Neoplasias del Cuello Uterino/secundario , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias Colorrectales/patología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/patología , Estudios Retrospectivos , Neoplasias Gástricas/patología , Análisis de Supervivencia , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/mortalidadRESUMEN
(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.
RESUMEN
Decitabine and azacitidine, two DNA methyltransferase (DNMT) inhibitors, are the current standard of treatment for myelodysplastic syndrome (MDS). Histone deacetylase (HDAC) inhibitors are also being tested against MDS. Both drug classes synergize in their gene reactivating and anticancer activities. The combination of hydralazine and valproate (Transkrip®), a DNMT and HDAC inhibitor, respectively), has been developed as epigenetic therapy under the drug repositioning concept. To evaluate the clinical efficacy and safety of hydralazine and valproate against MDS, an open phase-II study for previously treated patients with MDS was conducted. The hydralazine dose was given according with the acetylator phenotype, and valproate was dosed at 30 mg/kg/day. Response was graded with International Working Group criteria. Toxicity was evaluated by the Common Toxemia Criteria-National Cancer Institute version 3 scale. From November 2007 to January 2010, 12 patients were included. Median age±SD was 53±19.78 years (range, 23-79 years); median time from diagnosis to inclusion in the study was 7.9 months (range 2.6-36.1 months). Median of previous treatment was 2 (range, 1-6). Refractory cytopenia with multilineage dysplasia was diagnosed in ten cases, and refractory anemia with excess of blasts in two. Overall response was documented in six (50%) of 12 cases, including one CR, one PR, and four hematological improvements of the erythroid series. Two patients (16.6%) progressed to acute myeloid leukemia. Hemoglobin increased from 7.4 to 10.3 g/dL (in 13 weeks), neutrophils, from 1.1 to 2.0 (in 3 weeks), and platelets, from 66×10(9) to 72×10(9)/L (in 2 weeks). Transfusional requirements decreased from 2.3 to 0 U bi-monthly for red blood cells and from 0.5 to 0 U bi-monthly for platelets in responding patients. Main toxicities were mild, including somnolence and nausea. Preliminary results of this phase-II study suggest that the combination of hydralazine and valproate is a promising non-toxic and effective therapy for MDS.
Asunto(s)
Epigenómica , Hidralazina/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Ácido Valproico/uso terapéutico , Adulto , Anciano , Azacitidina/análogos & derivados , Azacitidina/uso terapéutico , Análisis Citogenético , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , Metilasas de Modificación del ADN/antagonistas & inhibidores , Decitabina , Femenino , Inhibidores de Histona Desacetilasas/sangre , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Hidralazina/sangre , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Resultado del Tratamiento , Ácido Valproico/sangre , Adulto JovenRESUMEN
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.
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.