Multidisciplinary diagnostics of chronic lymphocytic leukemia: European Research Initiative on CLL - ERIC recommendations

ABSTRACT Recent advances in chronic lymphocytic leukemia (CLL) includes description of disease genomic landscape, inclusion of prognostic relevant genetic tests in CLL workflow and evaluation of minimal residual disease (MRD)1 in parallel with the increase availability of novel therapy agents.In this review, the theoretical and practical aspects of response assessment have been discussed. These are based on updated recommendations of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) for genetic tests (TP53 mutation and IGHV status) and flow cytometry analysis for CLL. Methodological approaches and interpretation of results were also discussed.2,3

Histoplasmosis diseminada como manifestación inicial del linfoma linfocítico de células pequeñas / Disseminated histoplasmosis as a first clinical manifestation in a patient with small lymphocytic lymphoma: A case report

RESUMEN El linfoma linfocítico de células pequeñas es una neoplasia de células B maduras con un amplio espectro de presentaciones clínicas. Las infecciones por gérmenes oportunistas no asociadas con el tratamiento, incluso en estadios avanzados de la enfermedad, tienen baja incidencia. Se han reportado muy pocos casos de pacientes con linfoma linfocítico de células pequeñas asociado a histoplasmosis diseminada que no habían recibido quimioterapia en el momento del diagnóstico. Se presenta el caso de una paciente de 82 años que fue hospitalizada por presentar tos seca intermitente, astenia y adinamia de un mes de evolución. Se le practicaron múltiples estudios para detectar infecciones o compromiso inmunológico o reumático, y se diagnosticó un síndrome adenopático extenso con compromiso cervical, torácico y retroperitoneal. En la citometría de flujo y en la biopsia de ganglio linfático cervical, se reportaron los fenotipos CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg y CD10neg, con restricción de la cadena ligera kappa, lo cual confirmó un linfoma linfocítico de células pequeñas. En la histopatología del ganglio, se observaron granulomas epitelioides sin necrosis, pero las coloraciones especiales no mostraron la presencia de microorganismos, en tanto que el cultivo del ganglio fue positivo para Histoplasma capsulatum. Se inició el tratamiento antifúngico con anfotericina B e itraconazol, y la paciente tuvo una adecuada evolución. Dado que no se cumplían los criterios para el tratamiento oncológico, se continuó con su observación mediante controles periódicos. Las infecciones oportunistas pueden ser la manifestación clínica inicial en pacientes con síndromes linfoproliferativos de bajo grado. Este caso demuestra que pueden desarrollarse, incluso, en ausencia de quimioterapia.

ABSTRACT The small lymphocytic lymphoma is a mature B cell neoplasm with a broad spectrum of clinical presentations. Opportunistic infections that are not related to the treatment, even in advanced stages, have a low incidence rate. There are few case reports in the medical literature of patients who have not received immunosuppressive therapy and present with small lymphocytic lymphoma associated with disseminated histoplasmosis at diagnosis. A female 82-year-old patient was admitted due to an intermittent dry cough, asthenia, and adynamia that had persisted for one month. Multiple studies to detect infections and immuno-rheumatic conditions were performed and an extensive cervical, thoracic and peritoneal adenopathic syndrome was diagnosed. A flow cytometry and a cervical lymph node biopsy were performed reporting CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg, and CD10neg phenotypes with restriction in the light kappa chain compatible with a small lymphocytic lymphoma. Epithelioid granulomas without necrosis were observed in the lymph node histopathology and special colorations showed no microorganisms. The culture from the lymph node was positive for Histoplasma capsulatum. We initiated treatment with amphotericin B and itraconazole with an adequate response. In the absence of compliance with oncology treatment criteria, the patient was managed on a "watch and wait" basis. Opportunistic infections could be the initial clinical manifestation in patients with low-grade lymphoproliferative syndromes. This case report shows that they can develop even in the absence of chemotherapy.

Diagnosis and treatment of chronic lymphocytic leukemia: recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia

ABSTRACT Chronic lymphocytic leukemia is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+ and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood, lymph nodes, and spleen. The diagnosis is established by immunophenotyping circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai and Binet) established by physical examination and blood counts, as well as by several biological and genetic markers. In this update, we present the recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the diagnosis and treatment of chronic lymphocytic leukemia. The following recommendations are based on an extensive literature review with the aim of contributing to more uniform patient care in Brazil and possibly in other countries with a similar social-economic profile.

Esplenomegalia gigante en la leucemia linfocítica crónica / Giant splenomegaly in chronic lymphocytic leukemia

La leucemia linfocítica crónica constituye la forma de leucemia más frecuente en el mundo occidental; sus síntomas más frecuentes son la aparición de adenopatías, el cansancio, la pérdida de peso y aquellos derivados de las infecciones y del síndrome anémico. Aunque es una de las enfermedades que rara vez son tributarias de una esplenectomía por hiperesplenismo, es una entidad frecuente en hematología y debe ser del dominio y conocimiento del cirujano general. Presentamos un paciente con una esplenomegalia de proporciones gigantes, de inusual aparición(AU)

Chronic lymphocytic leukemia is the most frequent in the Western hemisphere; their symptoms usually include adenopathy, fatigue, loss weight and those derived from infection and anemic syndrome. Although it is one of the diseases rarely in need of splenectomy for hyperesplenism, it is a common pathology in hematology and they and general surgeon should have thorough knowledge about it. We introduced a patient with a splenomegaly of giant proportions and unusual presentation(AU)

Recent advances in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) was largely considered to be a disease of slow progression, standard treatment with Chlorambucil and having almost similar prognosis. With the introduction of molecular methods for understanding the disease pathophysiology in CLL there has been a remarkable change in the approach towards the disease. The variation in B-cell receptor response and immunoglobulin heavy chain variable region (IGHV) mutation, genetic aberration and defect in apoptosis and proliferation has had an impact on therapy initiation and prognosis. Early diagnosis of molecular variant is therefore necessary in CLL.

Prostatic adenocarcinoma and chronic lymphocytic leukemia: a case report

We report a rare case of a collision tumor. Our patient was found to have prostatic adenocarcinoma colliding with chronic lymphocytic leukemia, with no previous risk factors or even a clinical suspicion. We review the literature for similar cases and make an attempt to address the possible shared risk factors

Relato de caso de leucemia de células pilosas / Case report of hairy cell leukemia

A leucemia de células pilosas (LCP) é um tipo raro de linfoma não Hodgkin de células B. O quadro clínico inclui esplenomegalia, pancitopenia e linfocitose. Estudos de carcinogênese da doença revelam sua associação a agentes químicos agrícolas. O objetivo deste estudo foi o relato de um caso de paciente com LCP, masculino, tratorista, com pancitopenia, lesões de pele, sem esplenomegalia e com marcadores positivos para linfócitos B (CD19, CD20, CD22, CD79b, CD23, Lambda, imunoglobulina M [IgM], CD25 e CD103). Embora a LCP seja uma doença rara, a demora em seu diagnóstico pode levar a sérias complicações e à morte do paciente antes do diagnóstico.

Hairy cell leukemia (HCL) is a rare type of B-cell non-Hodgkin's lymphoma. The clinical symptoms include splenomegaly, pancytopenia, and lymphocytosis. Studies on its carcinogenesis reveal association with exposure to agricultural chemical agents. The objective of this study was to report the case of a male patient, tractor operator, diagnosed with HCL, pancytopenia, cutaneous lesions, without splenomegaly and positive markers for B-cell lymphocytes (CD19, CD20, CD22, CD79b, CD23, Lambda, immunoglobulin M [IgM], CD25 and CD103). Although HCL is a rare disease, late diagnosis may ultimately lead to severe complications and patient's death.

Monoclonal B-cell lymphocytosis: a brief review for general clinicians / Linfocitose monoclonal de células B: uma breve revisão para clínicos gerais

Monoclonal B-cell lymphocytosis (MBL) is a recently described medical condition that displays biological similarities to the most common subtype of adult leukemia in the Western world, i.e. chronic lymphocytic leukemia (CLL). Diagnostic criteria have been published with the aim of differentiating between these two entities. The overall prevalence of MBL is at least 100 times higher than that of CLL, which indirectly suggests that MBL is not necessarily a pre-leukemic condition, although in some circumstances, CLL cases can really be preceded by MBL. In view of this high prevalence rate, general clinicians and even non-hematological specialists have a high chance of being faced with individuals with MBL in their routine clinical practice. MBL is classified as "clinical MBL", "population-screening MBL" and "atypical MBL" and the clinical management of affected individuals depends greatly on this differentiation. The present review provides a guide to diagnosing and following up MBL patients.

A linfocitose monoclonal de células B (LMB) é uma condição médica recentemente descrita que exibe similaridades biológicas com o mais comum subtipo de leucemia em adultos de países ocidentais, qual seja, a leucemia linfocítica crônica (LLC). Critérios diagnósticos foram publicados com o intuito de separar as duas entidades. A prevalência global da LMB é pelo menos 100 vezes maior do que a da LLC, o que, indiretamente, sugere que a LMB não é necessariamente uma condição pré-leucêmica, embora, em algumas circunstâncias, casos de LLC possam realmente ser precedidos pela LMB. Em virtude dessa alta taxa de prevalência, clínicos gerais e mesmo outros especialistas não hematologistas têm grande chance de deparar-se com casos de LMB em suas rotinas clínicas. A LMB é classificada como "LMB clínica", "LMB de screening populacional" e "LMB atípica", sendo que o manuseio clínico dos indivíduos afetados depende substancialmente dessa diferenciação. A presente revisão fornece um guia para o diagnóstico e acompanhamento dos pacientes com LMB.

Correlation of del13q, del11q and trisomy 12 with laboratory and clinical features of chronic lymphocytic leukemia in Iranian patients

There is a strong association between chromosomal abnormalities and laboratory features and clinical course of the B-cell chronic lymphocytic leukemia [B-CLL]. The aim of this study was to investigate the frequency and correlation of cytogenetic aberrations with laboratory and clinical features of the disease. Clinical and laboratory features of 65 CLL patients were collected from their hospital profiles and their blood and/or bone marrow were examined by conventional cytogenetics and interphase FISH methods. Conventional cytogenetic methods identified 27.7% chromosomal abnormalities in 65 patients. I-FISH analysis for del13q, del11q and trisomy 12 revealed abnormality in 75.4% of patients. The results showed that IFISH improved the detection rate of chromosomal abnormalities and it enhanced detection. Statistical analysis was performed on sex, age, family history, Rai stage and CD markers on trisomy 12, del 11q and del 13q subgroups. There was a high frequency of Ray stages I and II within del13q subgroup, Rai stages III and IV within del11q subgroup and Rai stage II within trisomy 12 subgroup. Mean of CD38 in patients with del 11q was significantly higher than mean of patients with trisomy 12 and del 13q. High level of CD38 and presence of del11q indicated a poor prognosis and low level of CD38 and presence of del13q was indicative of good prognosis in Iranian B-CLL patients. Trisomy 12 had an intermediate prognostic value

Leucemia linfocítica crônica: classificação marcadores de risco e tratamento / Chronic lymphocytic leukemia: markers of risk classification and treatment

Revisão sobre leucemia linfocítica crônica, enfoque em estadiamento, novos marcadores prognósticos e novas abordagens terapêuticas.

Splenic lymphoma with villous lymphocytes.

Splenic lymphoma with villous lymphocytes (SLVL) is a rare disorder that comprises less than 1% of lymphoid neoplasms. It is the leukemic counterpart of splenic marginal zone lymphoma (SMZL) and is characterized by splenomegaly, often with no lymphadenopathy, moderate lymphocytosis and villous lymphocytes on peripheral blood smear. Here, we report a case of SLVL in a 56-year-old male with very high leukocyte counts, massive splenomegaly and relatively few leukemic cells with subtle villous projections on the surface. This disorder is often confused with other chronic lymphoproliferative disorders, especially chronic lymphocytic leukemia (CLL) and hairy cell leukemia and should be differentiated from them. We are reporting this case to highlight the diagnostic pitfalls associated with this disorder.

Epidemiologia de las leucemias en Bolivia: evaluación de 933 casos / Epidemiologia de las leucemias en Bolivia: evaluation of 933 cases

IntroducciónLa leucemia es el cáncer hematológico mas frecuente, su incidencia se ha incrementado en diferentes regiones del mundo. Los países en vías de desarrollo están experimentando el fenómeno de la “transición epidemiológica”, donde el cáncer ocupa una de las primeras causas de muerte. El presente trabajo describe las características epidemiológicas de las leucemias en Bolivia.MétodosSe estudiaron los datos epidemiológicos y resultados de diagnósticos de 983 muestras de pacientes con leucemia procedentes de diferentes Centros de Salud de Bolivia en fechas comprendidas entre enero de 1999 a junio de 2009. Todas las muestras fueron evaluadas con estudio morfológico e inmunofenotípico. En los pacientes con Leucemia Mieloide Crónica y Leucemia Mieloide Aguda - M3 se realizaron estudios biomoleculares. ResultadosDe los 933 pacientes con leucemia, 596 (64%) fueron niños y 337 (36%) adultos. De todos los pacientes 43% fueron mujeres y 57% varones. De acuerdo al diagnóstico la distribución fue la siguiente: Leucemia Linfoblástica Aguda 576 (61.8%), Leucemia Mieloblástica Aguda 217 (23,3%), Leucemia Linfocítica Crónica 18 (1.9%) y Leucemia Mieloide Crónica 122 (13%). ConclusiónLa distribución de leucemias en Bolivia tiene características propias en comparación a otros países, probablemente como expresión de la variedad poblacional multiétnica y pluricultural de Bolivia.

Introduction. Leukemia is the most common hematological cancer in the world; its incidence has increased in many regions around the world. The developing countries live through an epidemiological transition, where cancer will be the first cause of death in the next years. This study describes the epidemiological characteristics and diversity of leukemia in Bolivia. Methods. Epidemiological and laboratory data from 933 leukemia patients coming from different health centers in Bolivia, between January 1999 to June 2009 were included in the study. The diagnose was made by morphological and immunophenotypic assay and RT-PCR assay in chronic myeloid leukemia, and in acute myeloid leukemia M-3 was also performed.Results.The percent distribution of 933 patients, was: 43% women and 57% man. 64% were children and 36% adults. The morphological and immunophenotype diagnostic percentage distribution were: acute lymphoblastic leukemia 61,8% (576 patients), acute myelogenous leukemia 23,3% (217 patients), chronic lymphocytic leukemia 1.9% (18 patients) and chronic myeloid leukemia 13% (122 patients). Conclusion.The distribution of leukemia in Bolivia has different characteristics compared to other countries, probably as an expression of the multiethnic and multicultural population of Bolivia.

Estudo prognóstico em pacientes portadores de leucemia linfocítica crônica (LLC) / Prognostic factor in chronic lymphocytic leukemia (CLL)

Introdução e objetivo: a LLC, neoplasia clonal de células B, é a leucemia mais freqüente nos países ocidentais. Este trabalho avalia retrospectivamente as características clínicas dos portadores de LLC no Serviço de Hematologia do Hospital das Clínicas da UFMG. Metodologia: foram analisados os prontuários médicos de 77 pacientes com diagnóstico de LLC de 1992 a 2005. Resultados: dentre dos pacientes estudados 47 eram do sexo masculino (61%) e 30 (39%) do sexo feminino. A sobrevida média foi de 115 meses, a idade mediana de 65 anos, variando de 38 a 91 anos. A anormalidade citogenética mais freqüente foi a trissomia do 12, presente em 16% dos pacientes que apresentaram metáfases para análise. O sistema de estadiamento de Raí modificado foi o que melhor se correlacionou à sobrevida (p=0,001) e mostrou baixo risco – 21 pacientes (27,2%); risco intermediário – 36 pacientes (46,7%) e alto risco – 20 pacientes (25,9%), com sobrevida média de 154 meses, 65 meses e 43 meses, respectivamente. Entre as variáveis, nenhuma se mostrou significante em análise multivariada. Dez pacientes (13%) não haviam recebido quimioterapia até o momento do estudo e 67 (87%) foram tratados com esquemas de mono ou poliquimioterapia. Os pacientes tratados receberam clorambucil, fludarabina, fludarabina associada à ciclofostamida, COP, CHOP e radioterapia. Conclusão: não houve diferença significante na sobrevida entre as diversas formas de tratamento.

Expressão de Zap-70 e CD38 em leucemia linfocítica crônica (LLC) e sua correlação com prognóstico / Zap-70 and CD38 expression in CLL patients and the association with prognosis

Validar a imagem de difusão por ressonância magnética na predição do curso evolutivo do edema cerebral, e determinar sua natureza fisiopatológica em pacientes com eclâmpsia. Trinta e duas pacientes com eclâmpsia e lesões hiperintensas em T2 na ressonância magnética convencional foram avaliadas na admissão hospitalar e após oito semanas, segundo uma abordagem por paciente (n=32) e por segmento anatômico (n=103). A sensibilidade, especificidade, valores preditivos positivo e negativo, e acurácia foram / To validate diffusion-weighted magnetic resonance imaging in predicting the evolutive course of brain edema, and to establish its pathophysiology in patients with eclampsia. Thirty-two patients with eclampsia and T2 hyperintense brain lesions at routine magnetic resonance imaging were evaluated at hospital admission and eight weeks later either on a per-patient (n=32) and per-anatomical location basis (n=103). The sensitivity, specificity, positive and negative predictive values, and accuracy were...

Isolated Richter's syndrome in central nervous system: case report

Linfoma não Hodgkin difuso de grandes células em paciente portador de leucemia linfóide crônica (LLC), ou síndrome de Richter, é complicação rara e grave nesta leucemia. Síndrome de Richter isolada no sistema nervoso central é muito rara, tendo sido encontrados apenas 12 casos descritos. Descrevemos paciente de 74 anos, que apresentou linfoma não Hodgkin difuso de grandes células em região frontal direita, simulando glioblastoma multiforme.

Detection of CD5 in B-cell chronic lymphoproliferative diseases by flow cytometry: a strong expression in B-cell chronic lymphocytic leukemia

OBJETIVOS: CD5 é um marcador normalmente expresso nas células T e de forma aberrante nas células B da leucemia linfocítica crônica (LLC) e no linfoma de células do manto (LCM). Outras doenças linfoproliferativas crônicas como a hairy cell leukemia (HCL) e leukemia prolinfocítica de células B (LPL-B), são geralmente CD5 negativas ou expressam fracamente este antígeno. Neste trabalho investigou-se o padrão de expressão do CD5 em 42 pacientes com doenças linfoproliferativas crônicas de células B (DLC-B). METODOS: Investigamos a expressão de CD5 em células leucêmicas de 42 pacientes com DLC-B através da citometria de fluxo. Dados demográficos, tais como idade e sexo, bem como dados clínicos e laboratoriais também foram analisados. RESULTADOS: A imunofenotipagem mostrou que 35 casos foram LLC, 3 LPL-B, 3 HCL e um caso de LMC. O CD5 mostrou-se fortemente expresso em todos os casos de LLC e LMC. Baixa expressão desse antígeno foi observada em um caso de LPL-B, mostrando-se negativamente expresso em todos os casos de HCL. CONCLUSÃO: Nossos resultados demonstram que o padrão de expressão do CD5 pode auxiliar na distinção entre LLC da HCL e LPL-B, sendo no entanto similares na HCL e LCM.

ZAP-70: un nuevo factor pronóstico en la leucemia linfoide crónica / ZAP-70: a new prognostic factor in chronic lymphocytic leukemia

En la leucemia linfoide crónica de tipo B (LLC-B) se han planteado diferentes factores pronósticos para predecir la evolución de la enfermedad. En fecha reciente se ha añadido un nuevo factor pronóstico determinado por la expresión de una proteina de 70 Kda que se asocia con la cadena Z de receptor de las células T, y que se representa por la abreviatura ZAP-70. Esta proteína no se expresa en los linfocitos B normales, pero sí en los de un subgrupo de LLC-B que no tiene mutaciones en los genes de la región variable de la cadena pesada de las inmunoglobulinas (IgVH). Estudios recientes sugieren que la expresión de esta proteína en los linfocitos leucémicos podría contribuir a la evolución más agresiva que pueden tener las LLC-B sin mutaciones en los genes IgVH. Se ha señalado que la determinación de la ZAP-70 puede proporcionar un indicador pronóstico más simple que la caracterización del estado mutacional de los genes IgVH

Importância do cariótipo em leucemia linfocítica crônica: relato de 18 casos / Importance of karyotype in chronic lymphocytic leukemia: report of 18 cases

INTRODUÇAO: A leucemia linfocítica crônica (LLC) é doença neoplásica caracterizada pelo acúmulo de linfócitos B maduros CD 5, CD 19 e CD 23 positivos. Alterações cromossômicas têm sido descritas pela citogenética clássica em 30 por cento a 50 por cento dos casos de LLC. OBJETIVO: O objetivo do presente trabalho é demonstrar as alterações de cariótipo observadas em pacientes com LLC em nosso meio. PROCEDIMENTOS: Foram selecionados 18 casos de nosso arquivo, avaliados no período de quatro anos, com LLC diagnosticada com base nos achados morfológicos e imunofenotípicos. Havia 13 homens e cinco mulheres, uma relação de 2,6:1, com mediana de 63 anos. RESULTADOS: Foram detectadas alterações de cariótipo em 39 por cento dos casos (7/18). CONCLUSÕES: O cariótipo permitiu a identificação de diferentes clones em um grupo homogêneo de LLC sob os pontos de vista morfológico e imunofenotípico, demonstrando que as alterações genéticas são indicativas de comportamento biológico diferente.