Cytomegalovirus infection in transplant recipients.

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.

Cytomegalovirus infection in transplant recipients

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia. .

Dealing with bone marrow biopsies in the staging of classical Hodgkin lymphoma: an old issue revisited in the (18)F-fluorodeoxyglucose-positron emission tomography era.

Bone marrow biopsy is recommended for staging of classical Hodgkin lymphoma. The aim of this study was to compare bone marrow evaluation by histology with that obtained by (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET). One hundred and three cases of Classical Hodgkin Lymphoma were reviewed. All patients were submitted to FDG-PET evaluation. Bone marrow biopsy results were compared with clinical data and FDG-PET results. Ninety-one cases had available bone marrow biopsies. Overall, there were 16 positive and one suspect case. In five cases, the FDG-PET scan was positive and biopsy was negative: 1/5 was found to correspond to a bone fracture, 3/5 showed marked reactive bone marrow changes and in 1/5 no explanation for the discrepancy was found. FDG-PET showed high sensitivity, supporting the idea that when it is negative, biopsy could be avoided. Care should be taken in patients with a positive FDG-PET, where confirmation by bone marrow biopsy should be recommended.

Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15 percent to 20 percent of general patients and between 35 percent and 40 percent of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86 percent and 70 percent, respectively. The disease-free survival was approximately 60 percent at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported.

Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma.

BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported.

Anormalidades citogenéticas e sua relação com a proliferação e a apoptose celular em portadores de mieloma múltiplo / Cytogenetic abnormalities and their relation to cell proliferation and apoptosis in multiple myeloma patients

Anormalidades citogenéticas recorrentes são encontradas nas células tumorais de portadores de mieloma múltiplo. No momento do diagnóstico a t(4;14)(p16;q32) e a del(17p13) ocorrem em 10-20% e 5-10% dos casos, respectivamente, e são associadas à evolução clínica desfavorável. A del(13q14), por sua vez, ocorre em cerca de metade dos pacientes, porém não apresenta valor prognóstico importante. Entretanto, há evidências na literatura de que a del(13q14) seja um pré requisito para a expansão tumoral. O objetivo deste trabalho foi determinar a prevalência destas anormalidades cromossômicas em portadores de mieloma múltiplo recém diagnosticado e correlacioná-las com as taxas de proliferação e apoptose celular na medula óssea e a quantificação de plasmócitos em sangue. Amostras de aspirado de medula óssea provenientes de 84 portadores de mieloma múltiplo recém diagnosticado foram avaliadas quanto à presença de del(13q14), t(4;14)(p16;q32) e del(17p13) pela técnica de marcação fluorescente dos plasmócitos seguida pela hibridação in situ por fluorescência (cIg-FISH). Desta forma, foi realizada a correlação entre estas alterações e a quantificação de plasmócitos em sangue periférico, a proporção de plasmócitos positivos para o marcador de proliferação celular Ki-67 e para o marcador de apoptose anexina V, obtidos pela técnica de citometria de fluxo. Concomitantemente, foram avaliados parâmetros clínicos e laboratoriais e realizada a análise de sobrevida global (SG) e sobrevida livre de eventos (SLE). Os pacientes foram divididos em quatro grupos de acordo com a anormalidade citogenética presente: (1) grupo com t(4;14)(p16;q32), (2) grupo com del(17p13), (3) grupo com del(13q14) e sem nenhuma das outras alterações e (4) grupo sem nenhuma das anormalidades pesquisadas. Foi possível realizar a pesquisa de todas as anormalidades cromossômicas em 76 pacientes dos quais: vinte nove (38,1%) possuíam somente del(13q14), seis (7,89%) possuíam t(4;14)(p16;q32) e seis (7,89%)...

Recurrent cytogenetic abnormalities are found in multiple myeloma tumour cells. Among them, t(4;14)(p16;q32) e a del(17p13) occur respectively in 10-20% and 5-10% cases in the moment of diagnosis, and are associated with unfavorable clinical outcome. Del(13q14) occurs in half of patients, although, it has no important prognostic value. However, there are evidence in literature that del(13q14) is a pre requisite for tumour expansion. The purpose of this work was to determine the prevalence of chromosomal abnormalities in newly diagnosed multiple myeloma patients and correlate these abnormalities with the quantification of plasmocytes in blood and the rates of cellular proliferation and apoptosis. Bone marrow samples from eighty four newly diagnosed multiple myeloma patients were evaluated for the presence of del(13q14), t(4;14)(p16;q32) and del(17p13) by fluorescent in situ hybridization coupled to cytoplasmic staining of specific imunoglobulin (clg-FISH). Therefore, a correlation between these alterations and the proportion of plasmocytes positive for the proliferation antigen Ki-67 and for the apoptosis marker annexin V, measured by flow cytometry, was done. The quantification of plasmocytes in peripheral blood by flow cytometry was also made. Concurrently, clinical and laboratorial parameters, overall survival (OS) and event free survival (EFS) were also evaluated. Patients were divided in four groups accordingly to the cytogenetical abnormality present (1) t(4;14)(p16;q32), (2) del(17p13), (3) del(13q14) and none of the other alterations and (4) group with no researched abnormality. The research of all chromosomal abnormalities was possible in 76 patients: 29 (38,1%) had only del(13q14), six (7,89%) had t(4;14)(p16;q32) and six (7,89%) had del(17p13). No significant statistical difference was observed between different groups comparing the median expression of Ki-67 in plasmocytes (p=0,7), the median plasmocytes positive for annexin V (0,94)...

Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose for initial staging of hodgkin lymphoma: a single center experience in Brazil.

BACKGROUND: 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG-PET) is a well established functional imaging modality for the initial staging of Hodgkin lymphoma (HL) in patients from Western Europe and North America. The reliability of FDG-PET in populations of different ethnic groups is unclear, as all investigations published to date have come from developed countries. PURPOSE: The aim of the present study was to investigate the effectiveness of FDG-PET in the initial staging of HL patients in a Brazilian population. METHODS: Eighty-two patients with newly diagnosed HL were prospectively included in the study. All patients were staged with both conventional clinical staging (CCS) methods, including computed tomography (CT) and whole-body FDG-PET methods. A standard of reference for the nodal regions and the extranodal organs was determined using all available information, including the CCS methods, FDG-PET, the diagnostic histology and the follow-up examinations. The results of the CCS were then compared to the FDG-PET results. RESULTS: The sensitivity of FDG-PET was higher for nodal staging than that of CT (87.8% vs. 61.6%, respectively). FDG-PET was also more sensitive than CT in regard to evaluating the extranodal organs for lymphomatous involvement (96.2% vs. 40.0%, respectively). FDG-PET detected all 16 patients who were characterized by a positive bone marrow biopsy and identified an additional 4 patients with bone marrow disease. The incorporation of FDG-PET coupled with CCS in the staging procedure upstaged 20% (17/82) of the patients and downstaged 11% (9/82) of the patients. As a result of these changes in staging, 15% (13/82) of the patients would have received a different therapeutic regimen. CONCLUSIONS: The FDG-PET method is superior to CT for the detection of nodal and extra-nodal HL. The observation that the FDG-PET method upstaged the disease was the most common result (20% of patients) brought about by the addition of PET to the staging algorithm, even in a population of patients with a high incidence of advanced disease. However, changes in stages based on FDG-PET results should be confirmed by biopsy.

Positron emission tomography with 2-[18F]-Fluoro-2-Deoxy-D-Glucose for initial staging of hodgkin lymphoma: a single center experience in Brazil

BACKGROUND: 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG-PET) is a well established functional imaging modality for the initial staging of Hodgkin lymphoma (HL) in patients from Western Europe and North America. The reliability of FDG-PET in populationsof different ethnic groups is unclear, as all investigations published to date have come from developed countries. PURPOSE: The aim of the present study was to investigate the effectiveness of FDG-PET in the initial staging of HL patients in a Brazilian population. METHODS: Eighty-two patients with newly diagnosed HL were prospectively included in the study. All patients were staged with both conventional clinical staging (CCS) methods, including computed tomography (CT) and whole-body FDG-PET methods. A standard of reference for the nodal regions and the extranodal organs was determined using all available information, including the CCS methods, FDG-PET, the diagnostic histology and the follow-up examinations. The results of the CCS were then compared to the FDG-PET results. RESULTS: The sensitivity of FDG-PET was higher for nodal staging than that of CT (87.8% vs. 61.6%, respectively). FDG-PET was also more sensitive than CT in regard to evaluating the extranodal organs for lymphomatous involvement (96.2% vs. 40.0%, respectively). FDG-PET detected all 16 patients who were characterized by a positive bone marrow biopsy and identified an additional 4 patients with bone marrow disease. The incorporation of FDG-PET coupled with CCS in the staging procedure upstaged 20% (17/82) of the patients and downstaged 11% (9/82) of the patients. As a result of these changes in staging, 15% (13/82) of the patients would have received a different therapeutic regimen.CONCLUSIONS: The FDG-PET method is superior to CT for the detection of nodal and extra-nodal HL. The observation that the FDG-PET method upstaged the...

Diagnosis and treatment of polycythemia vera: Brazilian experience from a single institution.

CONTEXT AND OBJECTIVE: Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by predominant proliferation of erythroid precursors. Few data are available concerning Brazilian patients with this condition. The aim of this study was to describe clinical and demographic characteristics of PV patients at diagnosis and analyze their long-term outcomes. DESIGN AND SETTING: Retrospective study at the Division of Hematology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo. METHODS: All consecutive patients with PV diagnosed according to World Health Organization criteria were eligible for this study. Clinical and demographic characteristics, thrombotic events, transformation to acute leukemia, myelofibrosis and survival were evaluated. RESULTS: Sixty-six patients were evaluated. Thirty-six (54.5%) were females, with a median age at diagnosis of 61 years. At diagnosis, the median hemoglobin concentration was 18.8 mg/dl and the median platelet count was 593,000/mm(3). Fifty-eight patients (88.0%) were treated with hydroxyurea with or without phlebotomy. During a median follow-up of 77 months, 22 patients (33.3%) had new thrombotic events, mainly of arterial type. The overall incidence of leukemia and myelofibrosis was 0.42% per patient-year and 1.06% per patient-year, respectively. Median overall survival was not reached and the seven-year survival rate was 77.8%. CONCLUSION: The PV patients described here had long survival and arterial thrombotic events were the most important and common complication among this population.

Diagnosis and treatment of polycythemia vera: Brazilian experience from a single institution

CONTEXT AND OBJECTIVE: Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by predominant proliferation of erythroid precursors. Few data are available concerning Brazilian patients with this condition. The aim of this study was to describe clinical and demographic characteristics of PV patients at diagnosis and analyze their long-term outcomes. DESIGN AND SETTING: Retrospective study at the Division of Hematology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo. METHODS: All consecutive patients with PV diagnosed according to World Health Organization criteria were eligible for this study. Clinical and demographic characteristics, thrombotic events, transformation to acute leukemia, myelofibrosis and survival were evaluated. RESULTS: Sixty-six patients were evaluated. Thirty-six (54.5 percent) were females, with a median age at diagnosis of 61 years. At diagnosis, the median hemoglobin concentration was 18.8 mg/dl and the median platelet count was 593,000/mm³. Fifty-eight patients (88.0 percent) were treated with hydroxyurea with or without phlebotomy. During a median follow-up of 77 months, 22 patients (33.3 percent) had new thrombotic events, mainly of arterial type. The overall incidence of leukemia and myelofibrosis was 0.42 percent per patient-year and 1.06 percent per patient-year, respectively. Median overall survival was not reached and the seven-year survival rate was 77.8 percent. CONCLUSION: The PV patients described here had long survival and arterial thrombotic events were the most important and common complication among this population.

CONTEXTO E OBJETIVO: A policitemia vera (PV) é uma doença mieloproliferativa crônica, caracterizada pela proliferação de precursores hematopoéticos, principalmente da série eritróide. Poucos dados são disponíveis sobre pacientes brasileiros portadores desta doença. O objetivo do presente estudo é analisar as características de pacientes portadores de PV ao diagnóstico e a sua evolução clínica a longo prazo. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo unicêntrico, realizado no Serviço de Hematologia da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foram elegíveis para este estudo os pacientes com PV diagnosticados de acordo com os critérios estabelecidos pela Organização Mundial da Saúde. Foram avaliadas as características demográficas e clínicas ao diagnóstico, as complicações trombóticas, a transformação para leucemia aguda e mielofibrose e a sobrevida. RESULTADOS: Foram avaliados 66 pacientes; 36 (54,5 por cento) eram do sexo feminino, com uma mediana de idade ao diagnóstico de 61 anos. As medianas da concentração de hemoglobina e da plaquetometria ao diagnóstico foram de 18,8 mg/dl e 593.000/mm³, respectivamente. 58 (88,0 por cento) foram tratados com hidroxiuréia associada ou não à flebotomia. Em uma mediana de acompanhamento de 77 meses, 22 (33,3 por cento) pacientes apresentaram eventos trombóticos, predominantemente arteriais. A incidência de leucemia e mielofibrose foi de 0,42/100 pacientes-ano e 1,06/100 pacientes-ano, respectivamente. A mediana de sobrevida global não foi atingida, a taxa de sobrevida em sete anos foi de 77,8 por cento. CONCLUSÃO: Os portadores de PV em nosso serviço apresentaram longa sobrevida. Os eventos trombóticos arteriais foram a principal complicação da população estudada.