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1.
Leuk Lymphoma ; 61(13): 3188-3197, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32762271

RESUMO

We report final analysis outcomes from the phase 3 HELIOS study (NCT01611090). Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma without deletion 17p (n = 578) were randomized 1:1 to 420 mg daily ibrutinib or placebo plus ≤6 cycles of bendamustine plus rituximab (BR), followed by ibrutinib or placebo alone. Median follow-up was 63.7 months. Median investigator-assessed progression-free survival was longer with ibrutinib plus BR (65.1 months) than placebo plus BR (14.3 months; hazard ratio [HR] 0.229 [95% confidence interval (CI) 0.183-0.286]; p < .0001). Despite crossover of 63.3% of patients from the placebo plus BR arm to ibrutinib treatment upon disease progression, ibrutinib plus BR versus placebo plus BR demonstrated an overall survival benefit (HR 0.611 [95% CI 0.455-0.822]; p = .0010; median not reached in either arm). Long-term follow-up data confirm the survival benefit of ibrutinib plus BR over BR alone. Safety profiles were consistent with those known for ibrutinib and BR.

3.
J Glob Oncol ; 5: 1-19, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31774711

RESUMO

PURPOSE: Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL. METHODS: This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4). RESULTS: Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION: The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.


Assuntos
Leucemia Linfocítica Crônica de Células B/epidemiologia , Linfoma não Hodgkin/epidemiologia , Mieloma Múltiplo/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , América Latina/epidemiologia , Pessoa de Meia-Idade , Sistema de Registros , Adulto Jovem
4.
Medicina (B Aires) ; 77(3): 161-166, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-28643670

RESUMO

The expected five-year survival of chronic-phase chronic myeloid leukemia patients treated with tyrosine kinase inhibitors is over 90%. Little data is available regarding the results in the Argentinian population. This information might be of interest as generic imatinib is now available in the region. The aim of this study is to provide information on monitoring and the long-term treatment with imatinib outside of a controlled clinical trial, as well as to analyze the predictive effect of early responses to achieve molecular remission 4.0 (RM 4.0) and the detection of variables that may condition treatment failure. We included 106 patients, who received imatinib 400 mg daily as first-line inhibitor for a median of 8.9 years (IQR 5.8-11.7) between June 2000 and December, 2015. Overall survival was 93%. At latest follow-up 74% of patients continues on initial imatinib. The achievement of response at targeted milestones (6, 12 months) was associated with increased failure-free survival: 87% vs. 56%, p = 0.007; 90% vs. 69% p = 0.01 and was independently associated to RM 4.0: OR 5.6 (95% CI: 1.6-19.0); OR 5.3 (95% CI: 1.4-21.0) p = 0.006. After long-term follow-up, imatinib provided high-rates of response and survival. The prognostic value of response at targeted milestones was confirmed. This study reinforces the importance of molecular monitoring under IS standardization at known timepoints and this must continue to be a target in Argentina.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Sobrevida , Adulto Jovem
5.
Medicina (B.Aires) ; 77(3): 161-166, jun. 2017. graf, tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-894451

RESUMO

La supervivencia a cinco años de los pacientes con leucemia mieloide crónica en fase crónica tratados con inhibidores de tirosina quinasa es superior al 90%. Existen escasos datos a nivel local. Esta información puede ser de interés, ya que el imatinib genérico se encuentra disponible en la región. El objetivo del presente estudio es proporcionar información del monitoreo y los resultados a largo plazo del tratamiento con imatinib fuera de un ensayo clínico controlado, así como analizar el valor predictivo de respuestas tempranas para el logro de respuesta molecular 4.0 y la detección de variables que puedan condicionar falla al tratamiento. Se incluyeron 106 pacientes tratados con imatinib 400 mg diarios como inhibidor de primera línea durante una mediana de 8.9 años IQR (5.8-11.7) entre junio del 2000 y diciembre del 2015. La supervivencia global fue de 93%. En la última evaluación, 74% de los pacientes continuaba recibiendo el imatinib inicial. La obtención de respuesta en los objetivos temporales específicos (6, 12 meses) se asoció con mayor supervivencia libre de falla: 87% vs. 56%, p = 0.007; 90% vs. 69% p = 0.01 y mayor adquisición de respuesta molecular 4.0: OR 5.6 (IC 95% 1.6-19.0) p = 0.003; OR 5.3 (IC 95% 1.4-21.0) p = 0.006. Luego del prolongado seguimiento, el imatinib proporcionó altas tasas de respuesta y supervivencia. Se confirmó el valor pronóstico de la respuesta en momentos temporales específicos. Este estudio refuerza la importancia del monitoreo estandarizado en los puntos temporales conocidos, que debe continuar siendo un objetivo en Argentina.


The expected five-year survival of chronic-phase chronic myeloid leukemia patients treated with tyrosine kinase inhibitors is over 90%. Little data is available regarding the results in the Argentinian population. This information might be of interest as generic imatinib is now available in the region. The aim of this study is to provide information on monitoring and the long-term treatment with imatinib outside of a controlled clinical trial, as well as to analyze the predictive effect of early responses to achieve molecular remission 4.0 (RM 4.0) and the detection of variables that may condition treatment failure. We included 106 patients, who received imatinib 400 mg daily as first-line inhibitor for a median of 8.9 years (IQR 5.8-11.7) between June 2000 and December, 2015. Overall survival was 93%. At latest follow-up 74% of patients continues on initial imatinib. The achievement of response at targeted milestones (6, 12 months) was associated with increased failure-free survival: 87% vs. 56%, p = 0.007; 90% vs. 69% p = 0.01 and was independently associated to RM 4.0: OR 5.6 (95% CI: 1.6-19.0); OR 5.3 (95% CI: 1.4-21.0) p = 0.006. After long-term follow-up, imatinib provided high-rates of response and survival. The prognostic value of response at targeted milestones was confirmed. This study reinforces the importance of molecular monitoring under IS standardization at known timepoints and this must continue to be a target in Argentina.

6.
Genes Chromosomes Cancer ; 55(6): 531-40, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26998831

RESUMO

Mantle cell lymphoma (MCL) is a heterogeneous B-cell lymphoid malignancy where most patients follow an aggressive clinical course whereas others are associated with an indolent performance. SOX4, SOX11, and SOX12 belong to SOXC family of transcription factors involved in embryonic neurogenesis and tissue remodeling. Among them, SOX11 has been found aberrantly expressed in most aggressive MCL patients, being considered a reliable biomarker in the pathology. Several studies have revealed that microRNAs (miRs) from the miR-17-92 cluster are among the most deregulated miRNAs in human cancers, still little is known about this cluster in MCL. In this study we screened the transcriptional profiles of 70 MCL patients for SOXC cluster and miR17, miR18a, miR19b and miR92a, from the miR-17-92 cluster. Gene expression analysis showed higher SOX11 and SOX12 levels compared to SOX4 (P ≤ 0.0026). Moreover we found a negative correlation between the expression of SOX11 and SOX4 (P < 0.0001). miR17-92 cluster analysis showed that miR19b and miR92a exhibited higher levels than miR17 and miR18a (P < 0.0001). Unsupervised hierarchical clustering revealed two subgroups with significant differences in relation to aggressive MCL features, such as blastoid morphological variant (P = 0.0412), nodal presentation (P = 0.0492), CD5(+) (P = 0.0004) and shorter overall survival (P < 0.0001). Together, our findings show for the first time an association between the differential expression profiles of SOXC and miR17-92 clusters in MCL and also relate them to different clinical subtypes of the disease adding new biological information that may contribute to a better understanding of this pathology. © 2016 Wiley Periodicals, Inc.


Assuntos
Linfoma de Célula do Manto/genética , MicroRNAs/genética , Fatores de Transcrição SOXC/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/genética , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma de Célula do Manto/patologia , Masculino , MicroRNAs/biossíntese , Análise em Microsséries , Pessoa de Meia-Idade , Fatores de Transcrição SOXC/biossíntese , Análise de Sobrevida
7.
Lancet Oncol ; 17(2): 200-211, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26655421

RESUMO

BACKGROUND: Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. METHODS: The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression-free survival. Crossover to ibrutinib was permitted for patients in the placebo group with IRC-confirmed disease progression. Analysis was by intention-to-treat and is continuing for further long-term follow-up. The trial is registered with ClinicalTrials.gov, number NCT01611090. FINDINGS: Between Sept 19, 2012, and Jan 21, 2014, 578 eligible patients were randomly assigned to ibrutinib or placebo in combination with bendamustine plus rituximab (289 in each group). The primary endpoint was met at the preplanned interim analysis (March 10, 2015). At a median follow-up of 17 months (IQR 13·7-20·7), progression-free survival was significantly improved in the ibrutinib group compared with the placebo group (not reached in the ibrutinib group (95% CI not evaluable) vs 13·3 months (11·3-13·9) in the placebo group (hazard ratio [HR] 0·203, 95% CI 0·150-0·276; p<0·0001). IRC-assessed progression-free survival at 18 months was 79% (95% CI 73-83) in the ibrutinib group and 24% (18-31) in the placebo group (HR 0·203, 95% CI 0·150-0·276; p<0·0001). The most frequent all-grade adverse events were neutropenia and nausea. 222 (77%) of 287 patients in the ibrutinib group and 212 (74%) of 287 patients in the placebo group reported grade 3-4 events; the most common grade 3-4 adverse events in both groups were neutropenia (154 [54%] in the ibrutinib group vs 145 [51%] in the placebo group) and thrombocytopenia (43 [15%] in each group). A safety profile similar to that previously reported with ibrutinib and bendamustine plus rituximab individually was noted. INTERPRETATION: In patients eligible for bendamustine plus rituximab, the addition of ibrutinib to this regimen results in significant improvements in outcome with no new safety signals identified from the combination and a manageable safety profile. FUNDING: Janssen Research & Development.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hemorragia/induzido quimicamente , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fibrilação Atrial/induzido quimicamente , Cloridrato de Bendamustina/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Retratamento , Rituximab/administração & dosagem , Trombocitopenia/induzido quimicamente
8.
Cancer Invest ; 2015 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-26279306

RESUMO

This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.

9.
Cancer Invest ; 33(9): 451-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26288116

RESUMO

This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.


Assuntos
Genes abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Mutação/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
10.
Acta bioquím. clín. latinoam ; 47(1): 71-84, mar. 2013. ilus, graf
Artigo em Espanhol | LILACS | ID: lil-727421

RESUMO

La Gammapatía Monoclonal de Significado Incierto (GMSI) tiene una prevalencia que varía entre 1 y 3%, su frecuencia tiende a aumentar con la edad y aunque presentan evolución indolente y una sobrevida prolongada, un porcentaje de ellas desarrollará una enfermedad maligna. Con el objetivo de evaluar el valor pronóstico de diversos parámetros proteicos y hematológicos al momento del diagnóstico, se estudiaron mediante estudios proteicos completos en sangre y en orina, 407 pacientes con diagnóstico de GMSI que ingresaron a la institución en el período comprendido entre 1982 y 2008. La concentración del componente monoclonal (CM) (>1,5 g/dL) y el tipo inmunológico (No IgG), la disminución de las inmunoglobulinas no comprometidas (INC), el porcentaje de infiltración de células plasmáticas en médula ósea (>5%) y la mediana de las relaciones anormales de las cadenas livianas monoclonales libres, fueron los parámetros que marcaron riesgo de progresión a una enfermedad maligna. El estudio proteico completo de orina demostró una asociación entre el aumento en la concentración de proteínas de bajo peso molecular con valores de estimado de filtración glomerular menor de 60 mL/min/1,73 m2 y presencia de proteinuria de Bence Jones, independientemente del tipo de cadena liviana y de los niveles de proteínas totales. Debido a ello, la adición de dichos marcadores de daño tubular podría ofrecer una visión más profunda, siendo su aumento un posible indicador, en la profilaxis renal, de una severa lesión tubular futura. Finalmente, en pacientes con GMSI, los controles de laboratorio deberán ser ajustados en su periodicidad pero no en su contenido. La mayor información así obtenida será lo que permitirá una decisión médica más segura al momento de recomendar la frecuencia del seguimiento del paciente y la consiguiente detección temprana de una evolución maligna de la enfermedad.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Prognóstico
11.
Acta bioquím. clín. latinoam ; 47(1): 71-84, mar. 2013. ilus, graf, tab
Artigo em Espanhol | BINACIS | ID: bin-130990

RESUMO

La Gammapatía Monoclonal de Significado Incierto (GMSI) tiene una prevalencia que varía entre 1 y 3%, su frecuencia tiende a aumentar con la edad y aunque presentan evolución indolente y una sobrevida prolongada, un porcentaje de ellas desarrollará una enfermedad maligna. Con el objetivo de evaluar el valor pronóstico de diversos parámetros proteicos y hematológicos al momento del diagnóstico, se estudiaron mediante estudios proteicos completos en sangre y en orina, 407 pacientes con diagnóstico de GMSI que ingresaron a la institución en el período comprendido entre 1982 y 2008. La concentración del componente monoclonal (CM) (>1,5 g/dL) y el tipo inmunológico (No IgG), la disminución de las inmunoglobulinas no comprometidas (INC), el porcentaje de infiltración de células plasmáticas en médula ósea (>5%) y la mediana de las relaciones anormales de las cadenas livianas monoclonales libres, fueron los parámetros que marcaron riesgo de progresión a una enfermedad maligna. El estudio proteico completo de orina demostró una asociación entre el aumento en la concentración de proteínas de bajo peso molecular con valores de estimado de filtración glomerular menor de 60 mL/min/1,73 m2 y presencia de proteinuria de Bence Jones, independientemente del tipo de cadena liviana y de los niveles de proteínas totales. Debido a ello, la adición de dichos marcadores de daño tubular podría ofrecer una visión más profunda, siendo su aumento un posible indicador, en la profilaxis renal, de una severa lesión tubular futura. Finalmente, en pacientes con GMSI, los controles de laboratorio deberán ser ajustados en su periodicidad pero no en su contenido. La mayor información así obtenida será lo que permitirá una decisión médica más segura al momento de recomendar la frecuencia del seguimiento del paciente y la consiguiente detección temprana de una evolución maligna de la enfermedad.(AU)


Monoclonal gammopathy of undetermined significance (MGUS) is considered a premalignant state with a stable clinical course, and increased prevalence/risk of developing multiple myeloma (MM) or related malignancy according to age. To evaluate some hematologycal and protein parameters of prognostic value, 407 patients diagnosed as MGUS had been analyzed between 1982 to 2008 by means of complete urine and serum profile. A densitometry spike value (>1.5 g/dL), the monoclonal immunoglobulin class (No-IgG), the reduced concentration of non related immunoglobulin’s, the percentage of plasma cells in bone marrow (>5%) and an abnormal serum kappa/lambda free ratio; marked the increased risk of malignant progression. In urine, the presence of low molecular weight proteins has been associated with eGFR < 60 mL/min/1.73 m2 and the confirmation of Bence Jones proteinuria, independently of light chain type and the proteinuria level, reflecting a tubular damage. With an in deep view, a urine protein profile should detect an early renal compromise. We concluded that laboratory controls in patients with MGUS should be adjusted by periodicity but not in its content. A clear medical decision for the controls frequency or for establishing a worse outcome should be based on a complete protein profile evaluation.(AU)


A gamopatia monoclonal de significado indeterminado (GMSI) tem uma prevalÛncia variando de 1 a 3%, a sua frequÛncia tende a aumentar com a idade, apesar de apresentarem sobrevivÛncia indolentes e prolongada, uma percentagem de los a desenvolver uma doenþa maligna. A fim de avaliar o valor prognóstico da proteína vários parÔmetros hematológicos e no momento do diagnóstico, foram estudados 407 pacientes com diagnóstico de MGUS que foram internados em nossa instituiþÒo entre 1982 a 2008, com estudos de proteínas completas em sangue e urina. A concentraþÒo do componente monoclonal (CM) (>1,5 g/dL e imunológica (no IgG), diminuiþÒo da imunoglobulina nÒo confirmada (INC), a percentagem de infiltraþÒo de células de plasma na medula óssea (>5%) e mediana de relaþ§es anormais de cadeias leves livres monoclonais, foram os parÔmetros que marcaram risco de progressÒo para malignidade.O estudo de proteína total de urina mostraram que o aumento da concentraþÒo de proteínas de baixo peso molecular associados com valores estimados de filtraþÒo glomerular de menos de 60 mL/min/1.73 m2 e proteinúria Bence Jones, independentemente da cadeia leves e total níveis de proteína. Como resultado, a adiþÒo destes marcadores de dano tubular, pode oferecer um conhecimento mais profundo, e seu aumento um indicador possível para a profilaxia lesÒo tubular renal de futuro grave. Finalmente, em pacientes com GMSI, controles laboratoriais devem ser ajustados em frequÛncia, mas nÒo no conteúdo. A maioria da informaþÒo obtida será permitindo uma decisÒo médica mais segura quando recomendando a frequÛncia da monitorizaþÒo do paciente e, por conseguinte, a detecþÒo precoce de progressÒo maligna da doenþa.(AU)

12.
Acta bioquím. clín. latinoam ; 47(1): 71-84, mar.2013. ilus, graf
Artigo em Espanhol | BINACIS | ID: bin-129804

RESUMO

La Gammapatía Monoclonal de Significado Incierto (GMSI) tiene una prevalencia que varía entre 1 y 3%, su frecuencia tiende a aumentar con la edad y aunque presentan evolución indolente y una sobrevida prolongada, un porcentaje de ellas desarrollará una enfermedad maligna. Con el objetivo de evaluar el valor pronóstico de diversos parámetros proteicos y hematológicos al momento del diagnóstico, se estudiaron mediante estudios proteicos completos en sangre y en orina, 407 pacientes con diagnóstico de GMSI que ingresaron a la institución en el período comprendido entre 1982 y 2008. La concentración del componente monoclonal (CM) (>1,5 g/dL) y el tipo inmunológico (No IgG), la disminución de las inmunoglobulinas no comprometidas (INC), el porcentaje de infiltración de células plasmáticas en médula ósea (>5%) y la mediana de las relaciones anormales de las cadenas livianas monoclonales libres, fueron los parámetros que marcaron riesgo de progresión a una enfermedad maligna. El estudio proteico completo de orina demostró una asociación entre el aumento en la concentración de proteínas de bajo peso molecular con valores de estimado de filtración glomerular menor de 60 mL/min/1,73 m2 y presencia de proteinuria de Bence Jones, independientemente del tipo de cadena liviana y de los niveles de proteínas totales. Debido a ello, la adición de dichos marcadores de daño tubular podría ofrecer una visión más profunda, siendo su aumento un posible indicador, en la profilaxis renal, de una severa lesión tubular futura. Finalmente, en pacientes con GMSI, los controles de laboratorio deberán ser ajustados en su periodicidad pero no en su contenido. La mayor información así obtenida será lo que permitirá una decisión médica más segura al momento de recomendar la frecuencia del seguimiento del paciente y la consiguiente detección temprana de una evolución maligna de la enfermedad.(AU)


Assuntos
Prognóstico , Gamopatia Monoclonal de Significância Indeterminada
13.
Clin Chem Lab Med ; 50(6): 1093-7, 2012 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-22706252

RESUMO

BACKGROUND: To establish stringent complete remission (SCR) in patients with multiple myeloma (MM), it is currently recommended to obtain a normal serum free light chains (sFLC) ratio. The appearance of serum oligoclonal bands (OB) after autologous stem cell transplantation (ASCT) is considered a favorable prognostic factor. The objective of this study was to examine sFLC for assessing SCR in patients with MM, and ASCT with OB. We also examined how capillary electrophoresis (CE) compares with agarose gel electrophoresis (Aga) in identifying oligoclonal bands. METHODS: Out of 238 patients studied in our institution between April 1992 and December 2008 a serum protein electrophoresis (SPE) was performed by means of CE and sFLC determination on 37 patients with MM in complete remission (CR), ASCT and OB presence were assigned by conventional Aga electrophoresis and IF. RESULTS: Statistically significant differences (SSD) were found when comparing CE vs. Aga, regarding BO visualization in SPE, favoring the latter. In connection with sFLC, the group of patients with an abnormal ratio presented elevated values in the γ-globulin zone of the SPE, whereas the group of patients with a normal ratio of sFLC presented with normal values resulting in SSD between the groups. CONCLUSIONS: It is essential to perform immunofixation to certify the presence of OB, especially if CE is used as it is difficult to distinguish them using this method. A normal sFLC was observed in most of the patients with OB and normal values of the SPE γ-globulin zone. The above-mentioned information might demonstrate a limitation of sFLC test in SCR evaluation for patients with MM, ASCT and CR if OB has been detected.


Assuntos
Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/cirurgia , Bandas Oligoclonais/sangue , Transplante de Células-Tronco , Adulto , Idoso , Eletroforese Capilar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo
14.
Clin Lymphoma Myeloma Leuk ; 11(3): 280-5, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21658656

RESUMO

BACKGROUND: Monitoring minimal residual disease (MRD) by real-time quantitative polymerase chain reaction (RT-PCR) in chronic myeloid leukemia (CML) patients is mandatory in the era of tyrosine kinase inhibitors. Achieving a major molecular response (MMR) at 12 and 18 months predicts a better progression and event-free survival. PATIENTS AND METHODS: The objective of this prospective, multicentric study was to evaluate MRD by standardized RT-PCR in 178 patients with chronic-phase CML who were treated with imatinib at different institutions in Argentina and Uruguay and to determine if achievement of a stable MMR (BCR-ABL transcript levels < 0.1%) identifies a low-risk cytogenetic relapse group. The median age of the patients was 50 years, and 55% of them had received imatinib as first-line therapy. BCR-ABL transcript levels were measured after achievement of complete cytogenetic remission (CCyR) and at 6-month intervals. RESULTS: MMR was detected in 44% patients at the start of the study. This value increased to 79% at month 36 of evaluation. Complete molecular response (CMR) also increased from 24% to 52% of patients. Not achieving a stable MMR determined a higher risk of cytogenetic relapse (9% of MMR patients not achieving an MMR vs. 1% of patients who achieved MMR). Patients with sustained MMR had a significantly better cytogenetic relapse-free survival at 48 months (97% vs. 87%; P = .008) but showed no differences in overall survival. Patients who did not remain in CCyR changed treatment. CONCLUSIONS: A stable MMR is a strong predictor for a durable CCyR. Standardized molecular monitoring could replace cytogenetic analysis once CCyR is obtained. These results emphasize the validity and feasibility of molecular monitoring in all standardized medical centers of the world.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina , Benzamidas , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Prognóstico , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento , Uruguai , Adulto Jovem
15.
Clin Lymphoma Myeloma Leuk ; 10(3): 181-5, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20511162

RESUMO

BACKGROUND: Doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) plus involved-field radiation therapy (IFRT) is the gold-standard treatment for early and advanced stages of Hodgkin lymphoma (HL). We evaluated the outcomes of patients according to prognosis at diagnosis and over time to determine who achieved complete remission (CR). PATIENTS AND METHODS: Treatment-naive patients under the age of 75 years at all stages of HL were eligible. The favorable group (FG) contained patients with stage IA-IIIA disease without bulky areas who achieved CR after the third cycle of ABVD. They received only IFRT at 25 Gy. Patients in the unfavorable group (UG) exhibited stages IIIB and IV HL. The UG also included all patients with bulky disease and the subset of the FG without CR after 3 cycles of ABVD, ie, slow responders (FGSR). The UG received 6 cycles of ABVD plus IFRT at 30 Gy to bulky areas at diagnosis or to those areas remaining positive after the third cycle of ABVD. RESULTS: In total, 584 patients were evaluable: 285 of them belonged to the FG, and 299 to the UG. Rates of CR were 98% and 85% for the FG and the UG, respectively (P < .001). Sixty patients in the FG received 6 cycles of ABVD because they had not achieved CR after 3 cycles (ie, the FGSR subgroup). The 5-year event-free survival rate was 89% for the FG, 66% for the FGSR, and 72% for the UG (P < .001). The overall survival at 5 years was significantly better for the FG (98%) than for the FGSR (87%) and the UG (88%; P < .001). CONCLUSION: Patients from the FG demonstrated excellent outcomes compared with those from the FGSR and UG, despite receiving less chemotherapy and fewer doses of IFRT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/terapia , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Criança , Terapia Combinada , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia , Dosagem Radioterapêutica , Indução de Remissão , Fatores de Risco , Vimblastina/administração & dosagem , Adulto Jovem
16.
Clin Chem Lab Med ; 48(5): 727-31, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20450334

RESUMO

BACKGROUND: Over the last 20 years, high dose therapy followed by hemopoietic stem cell transplantation has been employed in patients with multiple myeloma (MM). During 16 years of follow-up, the degree of tumor response and survival in 238 patients with autologous stem cell transplantation (ASCT) and changes in the serum protein electrophoretic pattern were analyzed. METHODS: Agarose gel electrophoresis with densitometric analysis and immunofixation were performed to evaluate serum monoclonal protein. IgM, IgA, IgG and beta(2)-microglobulin (beta2M) were quantitated. Urine protein electrophoresis with IF was performed on cellulose acetate gel using colloidal silver staining without concentrating. RESULTS: After 34 months of follow-up (range 1-160 months), eight patients (3.4%) showed a distinct monoclonal protein band that was different from their original isotype switch. This was observed to be a transient phenomenon (22.2 months). Thirty-seven patients (15.5%) developed oligoclonal bands (OB) between the first and the twentieth month after ASCT (mean 4.4 months), which persisted for 7.9 months (1-36 months). The mean overall survival time was statistically different (p<0.05) between the group with OB and the group without them. Mean values of serum albumin, beta2M, and non-involved immunoglobulins did not show statistical differences. CONCLUSIONS: The occurrence of OB could be a potential favorable prognostic marker after transplantation due to the prolonged survival observed. Close follow-up of anomalous protein bands, either in serum or urine, is essential due to the additional difficulty in interpretation when the therapeutic response and evolution are evaluated.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Isotipos de Imunoglobulinas/sangue , Mieloma Múltiplo/terapia , Bandas Oligoclonais/sangue , Adulto , Idoso , Biomarcadores/sangue , Densitometria , Eletroforese em Gel de Ágar , Feminino , Seguimentos , Humanos , Focalização Isoelétrica , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Prognóstico , Transplante Autólogo
17.
Hematology ; 13(1): 24-7, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18534062

RESUMO

We studied the clinical impact of CD38 expression in 226 chronic lymphocytic leukemia patients (CLL) at disease presentation and during follow up to determine its prognostic significance, progression free survival (PFS) and overall survival (OS), and to verify whether this parameter changed over time. Various patients' characteristics were studied including gender, Rai and Binet stages, immunoglobulin light chain expression, lymphocyte doubling time and CD38 expression. After a median follow up of 53 months (range 6-282), 62% CD38 positive(+) patients required therapy. PFS and OS at 84 months were significantly lower for CD38(+) patients: 20 and 71% respectively, compared to CD38 negative(-): 70 and 96%. At multivariate analysis CD38(+) showed to be the best factor for predicting progression: HR 3.3, 95%CI 2.10-5.14, p = 0.000. Its expression did not change in 98% re-evaluated patients. We confirm that CD38(+) is a stable parameter for the identification of CLL patients with a more aggressive disease course.


Assuntos
ADP-Ribosil Ciclase 1/sangue , Leucemia Linfocítica Crônica de Células B/imunologia , Subpopulações de Linfócitos/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/classificação , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença
18.
Haematologica ; 93(1): 153-4, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18166806

RESUMO

A retrospective evaluation of 285 patients with monoclonal gammopathy of undetermined significance was performed to identify variables associated with progression, actuarial progression free survival (PFS) and overall survival (OS). Three variables, level of uninvolved immunoglobulins (HR 4.98, CI95% 2 -12.4, p=0.0006), monoclonal protein concentration (HR 4.04, CI95% 1.6-10.34, p=0.004), and erythrosedimentation rate (HR 3.94, CI95% 1.33-11.6, p=0.01), showed independent prognostic significance. With a median follow-up of 66 months (range 6-378), PFS and OS at 10 years were 89% and 91% respectively.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imunoglobulinas/metabolismo , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
Cytometry B Clin Cytom ; 70(2): 63-70, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16470534

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal disorders affecting hematopoietic progenitor cells (HPC). Despite the relevance of clonal CD34+ cells in developing MDS, only few studies analyze the phenotype of this cell population. The aim of this study was to evaluate phenotypic changes on HPC in MDS that could reflect abnormalities in the differentiation process of stem cells. METHODS: We analyzed the expression of CD38 and HLA-DR on CD34+ cells by flow cytometry in 36 patients with MDS, as well as in healthy donors (n = 12) and patients with other hematological disorders: non-Hodgkin lymphomas and multiple myeloma, both in complete remission (CR) (n = 32); acute lymphoblastic leukemia in CR (n = 17); de novo acute myeloblastic leukemia (AML) at diagnosis (n = 22) and in CR (n = 37); and AML secondary to MDS at diagnosis (n = 19). Cases with available karyotype were grouped according to the International Prognostic Scoring System (IPSS). RESULTS: Compared to normal BM, the fraction of immature HPC, characterized as CD34+bright, intermediate FSC/SSC, and CD38dim, was significantly increased in high risk MDS and secondary AML, but not in low risk MDS, (P < or = 0.001, P = 0.03, and P = 0.7). De novo AML showed decreased immature HPC. High numbers of immature HPC correlated with higher IPSS risk groups (P = 0.05) and showed significant impact on disease progression (P = 0.03). CONCLUSION: Our study confirms that evaluation of CD38 expression pattern on HPC is an easy and reproducible test that allows evaluating the immature subset of progenitor cells. Increased immature HPC in high risk MDS and secondary AML may reflect blocked differentiation of CD34+ cells in these diseases.


Assuntos
ADP-Ribosil Ciclase 1/imunologia , Antígenos CD34/imunologia , Células da Medula Óssea/imunologia , Células-Tronco Hematopoéticas/imunologia , Síndromes Mielodisplásicas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Progressão da Doença , Feminino , Citometria de Fluxo , Antígenos HLA-DR/imunologia , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/imunologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/imunologia , Síndromes Mielodisplásicas/diagnóstico , Variações Dependentes do Observador , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco
20.
Br J Haematol ; 127(2): 173-83, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15461623

RESUMO

Despite its recognition as a distinct, extremely rare entity, no large studies of intravascular lymphoma (IVL) have been reported. The clinico-pathological characteristics of 38 human immunodeficiency virus-negative patients with IVL diagnosed in Western countries were reviewed to better delineate clinical presentation, clinical variants, natural history and optimal therapy. The IVL is an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of cases) that predominantly affects elderly patients (median age 70 years, range: 34-90; male:female ratio 0.9), resulting in poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS >1 in 61%), B symptoms (55%), anaemia (63%) and high serum lactate dehydrogenase level (86%). The brain and skin are the most common sites of disease. In contrast to previous reports, hepatosplenic involvement (26%) and bone marrow infiltration (32%) were found to be common features in IVL, while nodal disease was confirmed as rare (11% of cases). Patients with disease limited to the skin ('cutaneous variant'; 26% of cases) were invariably females with a normal platelet count, and exhibited a significantly better outcome than the remaining patients, which deserves further investigation. Overall survival was usually poor; however, the early use of intensive therapies could improve outcome in young patients with unfavourable features. ECOG-PS >1, 'cutaneous variant', stage I and chemotherapy use were independently associated with improved survival.


Assuntos
Linfoma , Neoplasias Primárias Múltiplas , Neoplasias Vasculares , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Soronegatividade para HIV , Humanos , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Prognóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/mortalidade , Neoplasias Vasculares/patologia
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