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Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long-term outcome analysis on patients from the ITCLP with available 10-year follow-up data (n = 735). The overall response rate to first-line therapy was 68%, while 5- and 10-year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5- to 10-year period (67%). Low-risk International Prognostic Index and Prognostic Index for T-cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2-4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front-line therapeutic approaches in PTCLs.
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Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/tratamento farmacológico , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Seguimentos , Adulto , Estudos Prospectivos , Idoso de 80 Anos ou mais , Resultado do Tratamento , Prognóstico , Adulto Jovem , AdolescenteRESUMO
Classic Hodgkin lymphoma (HL) is rare disease, with an incidence of approximately 85,000 patients globally per year and a predilection for adolescents and young adults (ages 15-39). Since the introduction of combination chemotherapy in the 1960's and radiation dating back to the early 1900's, therapeutic options and by extension, clinical outcomes have improved dramatically with 5-year overall survival (OS) approaching 90% today. [1](#ref-0001) Advances in understanding HL biology have additionally facilitated development of targeted agents and immunotherapy which have further improved short and long-term outcomes. Despite continued improvements in up-front and salvage therapy, long-term survivors of HL experience several treatment-associated late toxicities, thus, along with efforts to improve therapeutic efficacy, efforts to reduce late effects remain a high-priority in the field.
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Follicular lymphoma is the most common indolent lymphoma accounting for approximately 20%-25% of all new non-Hodgkin lymphoma diagnoses in western countries. Whilst outcomes are mostly favorable, the spectrum of clinical phenotypes includes high-risk groups with significantly inferior outcomes. This review discusses recent updates in risk stratification and treatment approaches from upfront treatment for limited and advanced stage follicular lymphoma to the growing options for relapsed, refractory disease with perspectives on how to approach this from a personalized lens. Notable gaps remain on how one can precisely and prospectively select optimal treatment for patients based on varying risks, with an anticipation that an increased understanding of the biology of these different phenotypes and increasing refinement of imaging- and biomarker-based tools will, in time, allow these gaps to be closed.
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Chronic lymphocytic leukemia (CLL) is the most common mature B-cell neoplasm in the West. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome. In this study, we explored the mutational profile of CLL patients expressing IGHV4-34 within different stereotypes and their association with prognostic factors and clinical outcome. A multi-institutional cohort of unselected 1444 CLL patients was analyzed by RT-PCR and bidirectional sequencing. Cytogenetics and molecular cytogenetics analyses were also performed. We identified 144 (10%) IGHV4-34 expressing cases, 119 mutated (M), 44 of them with stereotyped B-cell receptors. Subset #4 was the most frequent (56.8% of cases) followed by subsets #16 (13.6%), #29 (6.8%), and #201 (2.3%), with different distribution among countries. Analysis of somatic hypermutation profile showed significant differences among stereotyped subsets for G28>D/E, P45>S, E55>Q, and S64>I changes (p < 0.01) and high frequency of disruption of the glycosylation motif in the VH CDR2 region. All stereotyped IGHV4-34 cases showed normal karyotypes. Deletion 13q14 as a sole alteration was present in 42.8% of stereotyped cases with a different distribution among subsets. A shorter time to first treatment was found in non-stereotyped vs. stereotyped M-IGHV4-34 patients (p = 0.034). Our results add new information supporting the importance of recurrent amino acid changes at particular positions, contributing to refine the molecular characterization of South American CLL patients.
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Cadeias Pesadas de Imunoglobulinas/genética , Leucemia Linfocítica Crônica de Células B/genética , Idoso , Estudos de Coortes , Feminino , Rearranjo Gênico , Humanos , Leucemia Linfocítica Crônica de Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação , Receptores de Antígenos de Linfócitos B/genética , Hipermutação Somática de Imunoglobulina , América do Sul/epidemiologiaRESUMO
Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in patients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.
El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RTPCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.
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COVID-19 , Hematologia , Argentina/epidemiologia , Teste para COVID-19 , Humanos , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
Abstract Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in pa tients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.
Resumen El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RT-PCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.
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Humanos , Pessoa de Meia-Idade , COVID-19 , Hematologia , Argentina/epidemiologia , Teste para COVID-19 , SARS-CoV-2RESUMO
Resumen Introducción: El linfoma de Hodgkin clásico presenta escasas células de Reed Sternberg/Hodgkin inmersas en un abundante microambiente tumoral. Los desbalances genómicos del locus 9p24.1 han sido asociados con alteraciones en la expresión de los genes del ligando de muerte celular 1 y 2, ambos reguladores de la respuesta inmune. Objetivo: Evaluar desbalances genómicos del locus 9p24.1 en células de Reed Sternberg/Hodgkin y del microambiente tumoral en biopsias de pacientes con linfoma de Hodgkin clásico y correlacionarlo con la expresión del ligando de muerte celular 1 y la presentación de la enfermedad. Materiales y Métodos: Se efectuó hibridación in situ en biopsias de 22 pacientes con linfoma de Hodgkin clásico dirigida a los genes del ligando de muerte celular 1 y 2. Las alteraciones se clasificaron en: amplificación, ganancia y polisomía. La expresión se evaluó mediante inmunohistoquímica. Resultados: Todos los pacientes mostraron alteraciones del número de copias. Se diferenciaron dos grupos: con amplificación (32%) y sin amplificación (68%); este último subdividido en: rico en ganancia (53%) y rico en polisomías (47%). El grupo rico en polisomías mostró mayor edad (p=0,027). El 40% de los pacientes con amplificación y rico en ganancias no presentó masa bulky. La expresión proteica mostró score +3 sólo en estos últimos. El title% de los casos ricos en polisomías presentaron monosomía del cromosoma 9 en los linfocitos circundantes respecto al 36,4% de los otros dos grupos. Conclusiones: Nuestros datos constituyen un aporte a la caracterización biológica del LHC, de interés en el marco de las nuevas modalidades terapéuticas. MÉD.UIS.2020;34(1):35-44.
Abstract Background: Classical Hodgkin lymphoma shows scarce tumor Reed-Sternberg/Hodgkin cells surrounded by a dense immune microenvironment. Genetic alterations at the 9p24.1 locus result in genomic imbalances in the copy number of PD-L1/PD-L2 genes, both of them being immune response regulators. Aim: To characterize genomic imbalances at the 9p24.1 locus in Reed-Sternberg/Hodgkin cells and immune microenvironment in biopsies of patients with Classical Hodgkin lymphoma and correlate it with PD-L1 protein expression and disease presentation. Material and Methods: Paraffin embedded biopsies of 22 patients with CHL were retrospectively evaluated by fluorescence in situ hybridization using SPEC CD274/PDCD1LG2/CEN9 DNA probe. The frequency of 9p24.1 alterations, amplification, copy gain and polysomy, were determined taking into account the number of gene copies with respect to the centromere. PD-L1 protein expression was evaluated by immunohistochemistry. Results: All cases presented alterations in the number of copies of PD-L1 / PD-L2, which are differentiated in two groups: with amplification (32%) and without amplification (68%). The latter was subdivided into rich in gains (RG) (53%) and rich in polysomies (RP) (47%). Groups with amplification and RG were younger than the RP group (p = 0.027). The latter was not associated with bulky disease, a fact observed in 40% of patients with amplification and RG. Protein expression showed score +3 only in the latter. All RP cases presented chromosome 9 monosomy in the surrounding lymphocytes, compared to 36.4% of the other two groups. Conclusions: Our data contributes to the biologic characterization of CHL, of interest in the context of new therapeutic modalities. MÉD.UIS.2020;34(1):35-44
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Humanos , Doença de Hodgkin , Expressão Gênica , Hibridização in Situ FluorescenteRESUMO
The treatment of classic Hodgkin lymphoma (HL) is a success in onco-hematology. Despite the high cure rate of HL with initial therapy, 5-10% of patients are primary refractory and 10-20% will eventually relapse. The standard treatment for these patients is salvage chemotherapy and autologous stem cell transplantation (ASCT). Only about half of these patients will benefit from this procedure. The prognosis of relapsed refractory (rr) HL has improved with the introduction of effective drugs. With these options available, identification of reliable risk factors is important to guide treatment over the course of disease. Different variables including performance status, anemia, B symptoms, laboratory abnormalities, treatment intensity before ASCT, response to therapy, and duration of remission, have been analyzed to determine risk for progression-free survival (PFS) and overall survival (OS) after ASCT. This review will discuss the publications analyzing these factors, the validated risk scores useful to identify patients at high risk of progression after ASCT, and will describe future perspectives.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/patologia , Terapia de Salvação/métodos , Quimiorradioterapia , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Doença de Hodgkin/patologia , Humanos , Prognóstico , Fatores de Risco , Transplante Autólogo , Resultado do TratamentoRESUMO
The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I-IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3-negative patients received no further therapy. PET3-positive patients received three additional cycles of ABVD plus involved-field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re-evaluated by PET scan (PET6). Study endpoints were 3-year progression-free survival (PFS) and overall survival (OS) rates. Two hundred and thirty-nine patients with early-stage and 138 with advanced-stage were evaluable. Overall, 260 patients (70%) were PET3-negative and had higher 3-year PFS (90% vs. 65%; P < 0·0001) and OS (98% vs. 92%; P = 0·007) rates than PET3-positive patients. All PET3-negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90-91%; P = 0·76) and OS (97-99%). The only independent prognostic factor for PFS was PET3-negativity (Hazard ratio 3·8; 95% confidence interval 2·4-6·3; P < 0·0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bleomicina/farmacologia , Bleomicina/uso terapêutico , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Vimblastina/farmacologia , Vimblastina/uso terapêutico , Adulto JovemRESUMO
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.
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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 , RNA Longo não Codificante , Fatores de Transcrição SOXC/biossíntese , Análise de SobrevidaRESUMO
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.
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Gamopatia Monoclonal de Significância Indeterminada , PrognósticoRESUMO
Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.
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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 AutólogoRESUMO
Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30 percent. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.
Assuntos
Humanos , Neoplasias Hematológicas , Células Matadoras Naturais , Linfoma de Células T/classificação , Linfoma de Células T/epidemiologia , Linfoma de Células T/patologia , PrognósticoRESUMO
El linfoma de Hodgkin es una neoplasia de linfocitos B de etiología desconocida. La nueva clasificación de la OMS muestra dos subtipos; el linfoma nodular con predominio linfocítico CD20 positivo, que representa el 5%, y la variedad clásica CD 15 y CD 30 positivo, con cuatro subvariedades. Ambos grupos se diferencian en su presentación clínica, inmunofenotipo, pronóstico y terapéutica. La nueva modalidad de evaluación por imágenes que fusiona un estudio metabólico, la tomografía por emisión de positrones (PET) con una tomografía anatómica convencional (PET-TC), logra predecir tempranamente en el curso del tratamiento el pronóstico de la enfermedad. Los pacientes con resultado negativo en la PET-TC luego de 1-4 ciclos tienen pronóstico más favorable. El objetivo actual del tratamiento inicial del linfoma de Hodgkin es lograr mantener los excelentes niveles de remisión completa, supervivencia libre de progresión y supervivencia global, reduciendo al máximo la toxicidad, especialmente gonadal, pulmonar y cardíaca, así como la aparición de segundas neoplasias. La quimioterapia óptima es la combinación ABVD con evaluación temprana por PET-TC; si el resultado es negativo se puede reducir el número de ciclos a 3 o 4 y evitar la radioterapia. En pacientes con persistencia de PET-TC positiva (<20%) es necesario intensificar el tratamiento para intentar mejorar su mal pronóstico. Con esta estrategia se logra una supervivencia a 5 y 10 años del 85% al 90%, con mínimos efectos tóxicos tardíos.
Assuntos
Humanos , Masculino , Adulto , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Tratamento Farmacológico , Tomografia por Emissão de PósitronsRESUMO
En Mieloma Múltiple (MM), el trasplante autólogo de médula ósea (TAMO) ofrece resultados superiores de remisión completa (RC), sobrevida global y sobrevida libre de eventos. Se evaluó el grado de respuesta, evolución y presentación de perfiles proteicos atípicos en 238 pacientes con MM y TAMO (abril/1992-diciembre/2007). Se realizaron sistemáticamente estudios proteicos completos en sangre y orina, pre y pos-trasplante. Con una media de seguimiento de 34 meses (1 -160 m) el 21.9 % presentaron RC, un 30.2 % remisión parcial, el 1.3% respuesta mínima y el 3.4 % enfermedad estable. Un 36.1 % tuvo recaída ó progresión y el 7.1 % no pudo ser evaluado. En el 15,5% se visualizaron bandas oligoclonales en el proteinograma y en la inmunofijación a los 4,4 meses promedio y duración promedio de 7,9 meses, observándose en ellos prolongada sobrevida. Ocho pacientes(3.4 %) evidenciaron un cambio en la expresión proteica de su MM a los 31.8 meses y duración de 22,2 meses promedio post- TAMO. El aporte del Laboratorio resulta de fundamental importancia, no sólo para el adecuado diagnóstico, sino además para establecer grado de respuesta y evolución y en la permanente búsqueda de nuevos parámetros de utilidad en el control de los pacientes con MM.
Assuntos
Transplante de Medula Óssea , Mieloma MúltiploRESUMO
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 DoençaRESUMO
BACKGROUND AND OBJECTIVES: This study explored variations in the clinical manifestations of intravascular lymphoma (IVL) on the bases of the association with hemophagocytosis and the country where the diagnosis was made. DESIGN AND METHODS: The clinical features of 50 Western patients with IVL were compared with those of 123 patients with IVL diagnosed in Eastern countries (87 diagnosed in Japan and 36 in other Asian countries), previously reported in English literature, and collected by an electronic bibliographic search. RESULTS: Hemophagocytosis was absent in Western patients, but reported in 38 (44%) Japanese patients (p=0.00001) and in seven (19%) patients from other Asian countries (p=0.002). No clinical differences were evident between patients with hemophagocytosis-negative IVL diagnosed in Western countries, Japan and other Asian Countries. Conversely, Japanese and non-Japanese patients with hemophagocytosis-related IVL more frequently had stage IV disease, fever, hepato-splenic involvement, marrow infiltration, dyspnea, anemia, and thrombocytopenia, and rarely exhibited cutaneous or central nervous system involvement. Lymph node and peripheral blood involvement was uncommon in all subgroups. In Western patients, anthracycline-based chemotherapy was associated with a 52% remission rate, and a 2-year overall survival of 46%. INTERPRETATION AND CONCLUSIONS: The clinical features of IVL vary according to the association with hemophagocytosis, regardless of the country in which the diagnosis is made. Western, Japanese and other Asian patients with hemophagocytosis-negative IVL display similar clinical characteristics and should be considered as having classical IVL. Patients with hemophagocytosis-related IVL show significantly different clinical features. Both forms have a poor prognosis. Extensive molecular studies are needed to explore whether these clinical differences might reflect discordant biological entities within IVL.
Assuntos
Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Neoplasias Vasculares/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ásia/epidemiologia , Povo Asiático/estatística & dados numéricos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Previsões , Humanos , Japão/etnologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etnologia , Linfo-Histiocitose Hemofagocítica/etiologia , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/etnologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Fenótipo , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Inquéritos e Questionários , Resultado do Tratamento , Neoplasias Vasculares/classificação , Neoplasias Vasculares/complicações , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/etnologia , Neoplasias Vasculares/patologia , População Branca/estatística & dados numéricosRESUMO
Thromboembolic events are an infrequent complication of hormonal treatment for infertility and are generally related to the hyperstimulated ovarian syndrome (HOS). Jugular vein thrombosis is an unusual site of thrombosis and when present one should look for a predisposing factor. We describe a 31-year-old woman, with no previous medical history, non-smoker, who received a single cycle of hormonal stimulation for in vitro fertilisation due to primary infertility. During her eighth week of a twin pregnancy, she consulted the emergency room where the diagnosis of bilateral jugular thrombosis was confirmed, in absence of HOS or any known predisposing factor. In subsequent studies, the presence of Factor V Leyden and a mutation of G 20210 prothrombin were found. These, in association to the hormonal stimulus, were considered the risk factors. She received anticoagulation treatment with low molecular weight heparin. Screening tests for thrombophilias before hormonal treatment is not recommended, but one could consider this possibility in high-risk patients or in those who develop thrombosis in the absence of any predisposing factors.
Assuntos
Veias Jugulares , Indução da Ovulação/efeitos adversos , Complicações Hematológicas na Gravidez/induzido quimicamente , Trombofilia/induzido quimicamente , Trombose Venosa/induzido quimicamente , Adulto , Anticoagulantes/uso terapêutico , Feminino , Fertilização in vitro , Gonadotropinas/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Mutação , Gravidez , Complicações Hematológicas na Gravidez/tratamento farmacológico , Protrombina/genética , Trombofilia/tratamento farmacológico , Gêmeos , Trombose Venosa/tratamento farmacológicoRESUMO
Thromboembolic events are an infrequent complication of hormonal treatment for infertility and are generally related to the hyperstimulated ovarian syndrome (HOS). Jugular vein thrombosis is an unusual site of thrombosis and when present one should look for a predisposing factor. We describe a 31-year-old woman, with no previous medical history, non-smoker, who received a single cycle of hormonal stimulation for in vitro fertilisation due to primary infertility. During her eighth week of a twin pregnancy, she consulted the emergency room where the diagnosis of bilateral jugular thrombosis was confirmed, in absence of HOS or any known predisposing factor. In subsequent studies, the presence of Factor V Leyden and a mutation of G 20210 prothrombin were found. These, in association to the hormonal stimulus, were considered the risk factors. She received anticoagulation treatment with low molecular weight heparin. Screening tests for thrombophilias before hormonal treatment is not recommended, but one could consider this possibility in high-risk patients or in those who develop thrombosis in the absence of any predisposing factors