Primary central nervous system lymphoma

O linfoma primário do sistema nervoso central (LPSNC) é um linfoma extralinfonodal que, ao diagnóstico, encontra-se restrito ao parênquima cerebral, às meninges e/ou cordão espinhal e/ou olhos. Sua incidência triplicou nas últimas três décadas para 0,4 casos por 100.000 habitantes, representando 4% dos tumores do sistema nervoso central (SNC). Embora pacientes infectados pelo HIV tenham 3.600 vezes maior risco para o desenvolvimento do LPSNC, a incidência não aumentou apenas neste grupo de pessoas. Dados sugerem reduções da incidência de LPSNC em pacientes infectados após a introdução de drogas anti-retrovirais. Cerca de 90% dos casos de LPSNC são classificados como linfoma difuso de grandes células B, 10% têm envolvimento ocular e 10% são HIV positivos. A apresentação clínica depende da localização tumoral, prevalecendo os sintomas neurológicos em detrimento aos sistêmicos. Os exames de tomografia computadorizada (TC) e ressonância nuclear magnética (RNM) são essenciais para o diagnóstico, porém o exame confirmatório deve ser o anatomopatológico. O estadiamento deve ser feito com exames de imagem e biópsia de medula óssea (BMO) bilateral. Os principais fatores de mau prognóstico são: performance status do paciente acima de 1, idade superior a 60 anos, DHL elevada, hiperproteinorraquia e acometimento de área cerebral não hemisférica. Alguns fatores de prognóstico biológicos também podem influenciar na sobrevida, a exemplo da expressão de Bcl-6, que confere melhor prognóstico. O tratamento de escolha é a combinação de quimioterapia contendo altas doses de metotrexate e radioterapia (RDT). Devido às altas taxas de neurotoxicidade associada à RDT, seu uso tem ficado mais restrito aos pacientes idosos, e os recidivados ou refratários.Primary Central Nervous System lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma in the brain, leptomeninges, spinal cord or eyes. The incidence of PCNSL increased approximately three-fold in the last decades. Nowadays, it represents 0.4 case per 100,000 people and accounts for 4% of all primary brain tumors. Although individuals infected with HIV have a 3,600-fold increased risk of developing PCNSL compared with the general population, the incidence has not increased only in AIDS group. Recent data suggest that the incidence of PCNSL declined in the AIDS group after the introduction of anti-retroviral drugs. Around 90% of PCNSL cases are classified as diffuse large B-cell lymphoma, 10% involve the eyes and 10% of patients are HIV positive. The clinical presentation depends on the location of the tumor with neurological rather than systemic symptoms. Computed tomography (CT) and magnetic resonance imaging (RMI) are essential in diagnosis, however the gold standard is tumor biopsy. Staging should be made with imaging and bilateral biopsy of bone marrow. The main poor prognosic parameters are performance status greater than 1, age older than 60 years, elevated DHL, high liquor protein concentration and tumor located within the deep regions of the brain. BCL-6 expression identified in the tumor confers a better prognosis. Currently, a combined therapy with high doses of methotrexate and whole-brain radiotherapy is the therapy of choice. Nowever, whole-brain radiotherapy should be carefully analyzed because neurotoxity is a frequent problem in the elderly and in relapsed and refractory patients

Is it necessary to perform a bilateral bone marrow biopsy to stage diffuse large B-cell lymphoma?

Estudo retrospectivo que visa analisar a utilidade da biópsia de medula óssea (BMO) bilateral na infiltração de medula óssea (MO) por linfoma difuso de grandes células B (LDGCB). Nossos objetivos foram avaliar a incidência de infiltração unilateral de MO por LDGCB e comparar o comprimento dos fragmentos obtidos entre as amostras positivas e negativas para infiltração. Além disso, verificamos se houve diferença entre os casos com infiltração unilateral versus bilateral, correlacionando com desidrogenase láctica (DHL) e estadiamento tomográfico. Avaliamos 268 casos de LDGCB e observamos infiltração medular em 34 casos (13%). Não foi possível a avaliação de seis casos, restando 28 casos para análise. Foram revisados no total 70 fragmentos de MO sobre presença ou ausência de infiltração e comprimento. A média do número de fragmentos por casos foi 2,5; a média do comprimento dos fragmentos foi 11,01 mm (± 5,12 mm), e a média do comprimento dos fragmentos por caso foi 27,53 mm. Foi observado que em seis casos (21,4%) havia infiltração unilateral. Não foram evidenciadas diferenças nas médias do comprimento dos fragmentos em relação à presença versus ausência de infiltração 10,95 mm (± 5,1 mm) versus 11,57 mm (± 5,2 mm), p > 0,05, respectivamente. Não foram evidenciadas diferenças em 23 casos entre a comparação da infiltração medular unilateral versus bilateral com DHL e estadiamento tomográfico. Concluímos que a BMO bilateral foi superior à unilateral, pois pode aumentar a detecção de infiltração de MO em 21,4% dos casos.This retrospective study aims to analyze the usefulness of bilateral bone marrow biopsy in bone marrow infiltration by diffuse large B-cell lymphoma (DLBCL). Our objectives were to assess the incidence of unilateral BM involvement by DLBCL and compare fragment length obtained from positive and negative samples for infiltration. Furthermore, we compared the differences between unilateral and bilateral infiltration correlating with lactic dehydrogenase (LDH) and computerized tomography (CT) staging. We evaluated 268 cases of DLBCL and observed medullary infiltration in 34 cases (13%). It was not possible to evaluate 6 out of 34 cases. 70 BM fragments were reviewed as to the presence or absence of infiltration and length. The mean number of fragments per case was 2.5; the mean BM fragment length was 11.01 mm (± 5.12 mm) and the mean BM fragment length per case was 27.53 mm. There was unilateral BM infiltration in six cases (21.4%). There were no differences in the mean fragment length as to the presence/absence of infiltration 10.95 mm (± 5.2 mm) versus 11.57 mm, p > 0.05, respectively. There were no differences in 23 cases between the comparison of unilateral medullary infiltration versus bilateral with lactic dehydrogenase and CT staging. We concluded that bilateral bone marrow biopsy was superior to unilateral because it may increase by 21.4% the detection of BM involvement by DLBCL

Disease progression after R-CHOP treatment associated with the loss of CD20 antigen expression

A case of a follicular lymphoma transformed into a CD20+ is described which progressed with the loss of CD20 expression after 8 cycles of R-CHOP. This phenomenon is not a rare event and has shown poor prognosis. Our purposes are to describe this event and suggest biopsy in relapsed or progressive disease

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m2, for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4x109/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment dueto liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

Outpatient therapy for patients with febrile neutropenia

INTRODUÇÃO: A neutropenia febril (NF) é uma complicação freqüente e potencialmente fatal no manejo do paciente onco-hematológico. Estudos recentes demonstram que a NF consiste em um grupo heterogêneo de pacientes com riscos variados. Nosso objetivo foi avaliar a taxa de falência ao tratamento de primeira linha, taxa de internação e óbito. Além disso, estudamos as variáveis clínico-laboratoriais em relação aos desfechos, a validação do índice Multinational Association for Supportive Care of Cancer (MASCC) modificado e a taxa de positividade de hemocultura e urocultura, como também o perfil de sensibilidade ao cefepima. CASUÍSTICA E METODOLOGIA: Estudo retrospectivo unicêntrico. Os dados foram obtidos através dos prontuários do Hospital-Dia no período de Julho de 2001 a Junho de 2006. Foram avaliados eventos com NF tratados com cefepima 2g (2x/dia), associado ou não, a teicoplamina 400mg/dia. RESULTADOS: Em 128 pacientes, estudamos 178 eventos de NF. A taxa de falência ao tratamento de primeira linha foi de 36,5%, taxa de internação 20,7% e óbito em 6,2% entre os eventos de NF. Na análise multivariada do estudo das categorias clínico-laboratoriais e dos desfechos encontramos como dados significantes em relação ao risco da falência ao tratamento de primeira linha: Idade 1,2mg/dL (OR: 7,19, IC95%: 1,81 30,71 p= 0,005). Os dados significantes para o risco de internação foram: Ausência do diagnóstico de Linfoma não - Hodgkin (OR: 2,42 IC95%: 2,04 2,8, p= 0,011) Tabagismo (OR: 3,14, IC95% 1,14 8,66, p=0,027) e creatinina sérica > 1,2mg/dL (OR: 7,97, IC95% 21,19 - 28,95, p=0,002). Em relação ao óbito, o único dado de risco significante foi a saturação de oxigênio 1,2mg/dL e oximetria de pulso 1,2mg/mL (OR: 7,19, CI95%: 1,81 30,71 p= 0,005). In hospitalization the risks were: Without diagnosis of Non- Hodgkin Lymphoma (OR: 2,42, CI95%: 2,04 2,8, p= 0,011), smoking (OR: 3,14, CI95% 1,14 8,66, p=0,027), serum creatinine > 1,2mg/dL (OR: 7,97, CI95%21,19- 28,95, p=0,002). Relating to death, the risk was transcutaneous oximetry < 95% (OR: 5.8, CI95%: 1.50 22.56, p = 0.011). Analyzing MASCC index, 165 events were classified as low-risk and 13 as high-risk. Outpatient treatment failures were reported in connection with 7 (53.8%) high-risk episodes and 30 (18.2%) low-risk, p=0.006. In addition, death in 7 (4.2%) low-risk and 4 (30.8%) high-risk events, p=0.004. Microbiological infection documented was identified in 13% and 8% in blood cultures and urine cultures, respectively. The most common agent isolated was E. coli and 100% were sensitive to cefepime. INTERPRETATIONS AND CONCLUSIONS: The outpatient treatment with intravenous antibiotic was satisfactory. The risks: Haematologic malignancies other than Non-Hodgkin Lymphoma, smoking, serum creatinine elevated and oximetry < 95% should be considered in FN evaluation. It was validated MASCC index in the Brazilian population. Relating to microbiological agents studied 100% were not resistant for cefepime

Atypical chronic myeloid leukemia with t(9;22)(p24,11.2), a BCR-JAK2 fusion gene

We report here on a rare case of BCR-ABL1-negative atypical chronic myeloid leukemia with a t(9;22)(p24;q11.2)translocation and a BCR-JAK2 fusion gene, with resistance to the tyrosine kinase inhibitors imatinib and dasatinib.At two years of follow-up, the patient showed no hematologic response and was submitted to an allogeneic bonemarrow transplantation. Fifty-three days after the procedure, he died due to acute graft-versus-host disease. This BCR-JAK2 fusion gene has so far been found in only five patients in the whole world, with three clinical presentations: myeloproliferative neoplasm, acute lymphoblastic leukemia and acute myeloid leukemia