Lymphoma: streamlining follow ups

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Herpes zoster after autologous hematopoietic stem cell transplantation

Background: The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. Methods:A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. Results: Fourteen (6.1%) patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3%) were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection (p-value = 0.002). There were no significant differences for the other variables analyzed. Conclusion: The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.

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.

Frequência da proteína Bcl-2 em pacientes com linfoma difuso de grandes células B de alto risco

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9%) were GCB-like and 49 (67.1%) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37%) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37% of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.CONTEXTO E OBJETIVO: A expressão gênica e imunoistoquímica do linfoma difuso de grandes células B (LDGCB) vem permitindo a identificação de importantes subgrupos prognósticos: LDGCB do centro germinativo (CG) e LDGCB de células B ativadas (CBA). Entretanto, existem poucos dados disponíveis com LDGCB de alto risco, sendo o prognóstico dos LDGCB do CG melhor que os LDGCB de CBA. A participação do Bcl-2 como preditor de sobrevida nos LDGCB não é clara e sua expressão é variável entre os dois subgrupos de LDGCB. Neste estudo é avaliada a frequência e o prognóstico da expressão da proteína Bcl-2 em LDGCB de alto risco. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo realizado entre portadores de LDGCB tratados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foi avaliado o impacto prognóstico da expressão das proteínas CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) e Bcl-2 por imunoistoquímica em LDGCB de alto risco. Foram avaliados, para todos os marcadores, 73 pacientes com idade de 18 a 60 anos. RESULTADOS: Vinte e quatro (32,9%) pacientes foram classificados como LDGCB do CG e 49 (67,1%) como LDGCB de CBA, sem diferença nas taxas de remissão completa, sobrevida livre de doença e sobrevida global. Vinte e sete (37%) apresentaram expressão de Bcl-2, o qual foi o único fator preditivo independente de pior prognóstico de sobrevida global à análise multivariada. CONCLUSÃO: A expressão da proteína Bcl-2 ocorreu em 37% dos portadores de LDGCB de alto risco, sem diferença entre os subgrupos de LDGCB do CG ou de CBA

Cirrose biliar primária e miopatia: uma rara associação

Primary biliary cirrhosis (PBC) is a cholestatic liver disease, which is characterized by a chronic inflammatory destruction of intrahepatic bile ducts. It is a rare disorder whose precise etiology is still to be elucidated. Even though the liver is the principal target of PBC, other organ systems also might be affected. Muscular involvement has rarely been described in this disease, and in the majority of cases, muscular weakness has been interpreted as polymyositis. We report the case of a 48-year-old woman suffering from classic PBC, in association with a myopathy whose histological features are distinct from the cases reported before. We also performed a MEDLINE research for PBC and concomitant muscular diseases.A cirrose biliar primária (CBP) é uma doença hepática colestática crônica de etiologia desconhecida e rara. Apesar do principal órgão acometido na CBP ser o fígado, outros órgãos podem também ser afetados. O acometimento muscular raramente tem sido relatado em pacientes com CBP e na maioria destes casos, a fraqueza muscular tem sido interpretada como Polimiosite. Nós relatamos o caso de uma mulher de 48 anos com CBP e miopatia com achados histopatológicos distintos dos casos anteriormente descritos e fizemos uma revisão da literatura sobre o acometimento muscular na CBP

Observational Study of prognosis and therapeutics of Diffuse Large B Cell Lymphoma patients with high intermediate to high aIPI risk

Pacientes com linfoma difuso de grande célula B (LDGCB) do mesmo grupo de risco pelos critérios do Índice de Prognóstico Internacional (IPI), tratados com quimioterapia convencional à base de antraciclina, podem ter resposta terapêutica não esperada para seu grupo de risco. Isso pode ser explicado pelo fato do prognóstico dos LDGCB, que têm origem no centro germinativo (CG), ser superior aos originados após o CG (NCG). No intuito de aprimorar a avaliação de prognóstico e a abordagem terapêutica em LDGCB de IPI ajustado para a idade (IPIa) de risco intermediário alto e alto, elaboramos projeto de pesquisa, para verificar o papel dos marcadores imuno-histoquímicos (IH) e do transplante de medula óssea autólogo (ATMO), em primeira remissão completa (RC), neste grupo de pacientes. Avaliamos o impacto da expressão dos marcadores CD10, Bcl-6, MUM-1, Bcl-2 e p63 na obtenção de RC, sobrevida livre de doença (SLD) e sobrevida global (SG), isoladamente e de acordo com a origem em CG e NCG. Avaliamos 82 pacientes abaixo dos 60 anos, dos quais 16 (19,5%) receberam ATMO em primeira RC, além de serem comparados com os pacientes tratados com quimioterapia convencional e mantidos em observação após RC. A IH foi avaliável em 73 casos, 24 (32,9%) tiveram origem no CG e 49 (67,1%) NCG, sem diferença de sobrevida entre os grupos. A proteína Bcl-2 foi positiva em 27 (37%) pacientes e foi o único fator preditivo independente para SG à análise multivariada, com tendência de significância para RC. As SG e SLD em cinco anos para os 16 pacientes que receberam ATMO foi de 75% e 85,2%, respectivamente, a taxa de recidiva de 6,5% e diferença estatisticamente significativa para SLD (p = 0,015) em comparação aos pacientes apenas observados. Concluímos que o ATMO foi seguro e capaz de melhorar a sobrevida em LDGCB de risco intermediário alto e alto, e que a expressão de Bcl-2 pode ser utilizada na programação terapêutica inicial desses pacientes.Diffuse large B cell lymphoma (DLBCL) patients from the same risk group according to the International Prognostic Index (IPI) treated with conventional anthracycline-based chemotherapy may show an unexpected therapeutic response. This can be explained by the fact that the prognosis of DLBCL originating in germinal center (GC) cells is superior than that originating out of germinal center (NGC). In order to improve the prognostic evaluation and the therapeutic approach to DLBCL patients with high intermediate to high age-adjusted IPI (aIPI), a research project was designed for the analysis of immunohistochemical markers and the role of autologous stem cell transplantation (ASCT) in first complete remission (CR) for this group of patients. The impact of the expression of CD10, Bcl-6, MUM-1, Bcl-2 and p63 markers on complete remission (CR), disease-free survival (DFS) and overall survival (OS), either individually and according to cell origin was evaluated by means of immunohistochemistry. Eighty-two patients aged under 60 years old were assessed, of which 16 (19.5%) underwent ASCT in first CR and were compared to patients receiving conventional chemotherapy and being monitored after CR. Immunohistochemistry was assessable in 73 cases, 24 (32.9%) being classified as GC-type and 49 (67.1%) as NGC-type, with no survival difference between the two groups. Bcl-2 expression was found in 37% (27) of the patients and was the single independent predicting factor of OS prognosis according to multivariate analysis. A significant tendency of expression of this protein was also observed for achieving CR, which was essential for longer survival, as shown by multivariate analysis. OS and DFS within 5 years were of 75% and 85.2% respectively for the group of 16 patients treated with ASCT, which resulted in lower relapse rates (6.5%) with statistically significant difference for DFS (p=0.015) when compared to the group of patients who achieved CR and was kept under monitoring. In this study ASCT was found to be a safe procedure for improving survival rates of DLBCL patients with high intermediate to high aIPI risk. Also, the expression of Bcl-2 protein was found to be useful as one of the variables to be analysed in the therapeutic approach to these patient