Need for hemodialysis in patients undergoing hematopoietic stem cell transplantation: risk factors and survival in a retrospective cohort

ABSTRACT Introduction: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) patients are exposed to acute and chronic nephrotoxic events (drugs, hypotension, infections, and microangiopathy). The need for hemodialysis (HD) may be associated with high mortality rates. However, the risk factors and clinical impact of HD are poorly understood. Aim: To analyze survival and risk factors associated with HD in allo-HSCT Patients and methods: single-center cohort study 185 (34 HD cases versus 151 controls) consecutive adult allo-HSCT patients from 2007-2019. We performed univariate statistical analysis, then logistic regression and competing risk regression were used to multivariate analysis. Survival was analyzed by Kaplan-Meier and Cox proportional-hazards models. Results: The one-year HD cumulative incidence was 17.6%. Univariate analysis revealed that HD was significantly associated with male gender, age (p 0.056), haploidentical donor, grade II-IV acute GVHD, polymyxin B, amikacin, cidofovir, microangiopathy, septic shock (norepinephrine use) and steroid exposure. The median days of glycopeptides exposure (teicoplanin/vancomycin) was 16 (HD) versus 10 (no HD) (p 0.088). In multivariate analysis, we found: norepinephrine (hazard ratio, HR:3.3; 95% confidence interval, 95%CI:1.2-8.9; p 0.024), cidofovir drug (HR:11.0; 95%CI:4.6 - 26.0; p < 0.001), haploidentical HSCT (HR:1.94; 95%CI:0.81-4.65; p 0.14) and Age (HR:1.01; 95%CI: 0.99-1.03; p 0.18). The HD group had higher mortality rate (HR:6.68; 95% CI: 4.1-10.9; p < 0.001). Conclusion: HD was associated with decreased survival in allo-HSCT. Carefully use of nephrotoxic drugs and improving immune reconstitution could reduce severe infections (shock) and patients requiring cidofovir, which taken together may result in lower rates of HD, therefore improving survival.

Molecular profile of patients with myelofibrosis: a 10-year experience

ABSTRACT Objective To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. Methods Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. Results A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). Conclusion The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

Diagnosis and treatment of systemic mastocytosis in Brazil: Recommendations of a multidisciplinary expert panel

ABSTRACT Introduction: Systemic Mastocytosis comprises a group of neoplastic diseases characterized by clonal expansion and infiltration of mast cells into several organs. The diagnosis and treatment of this disease may be challenging for non-specialists. Objective: Make suggestions or recommendations in Systemic Mastocytosis based in a panel of Brazilian specialists. Method and results: An online expert panel with 18 multidisciplinary specialists was convened to propose recommendations on the diagnosis and treatment of Systemic Mastocytosis in Brazil. Recommendations were based on discussions of topics and multiple-choice questions and were graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Chart. Conclusion: Twenty-two recommendations or suggestions were proposed based on a literature review and graded according to the findings.

Guidelines for therapy of patients with chronic myeloproliferative neoplasms during the novel coronavirus SARS-CoV2 pandemic

ABSTRACT The novel coronavirus has swept across the world in 2020 and ushered a new era. In the current scenario, it is not clear how patients with myeloproliferative neoplasms (including chronic myelogenous leukemia) should be managed, considering the risk of therapy, the need for social distancing and the risk of untimely therapy discontinuation of delay. This guideline aims to give providers a sense of direction in order to better take care of patients and prioritize care.

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Elderly / Consenso Brasileiro de Nutrição em Transplante de Células-Tronco Hematopoiéticas: Idosos

ABSTRACT The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Elderly was elaborated by nutritionists, nutrologists and hematologists physicians from 15 Brazilians reference centers in hematopoietic stem cell transplantation, in order to emphasize the importancy of nutritional status and the body composition during the treatment, as well as the main characteristics related to patient's nutritional assessment. Establishing the consensus, we intended to improve and standardize the nutritional therapy during the hematopoietic stem cell transplantation. The Consensus was approved by the Brazilian Society of Bone Marrow Transplantation.

RESUMO O Consenso Brasileiro de Nutrição em Transplante de Células-Tronco Hematopoiéticas: Idoso foi elaborado com a participação de nutricionistas, médicos nutrólogos e médicos hematologistas de 15 centros brasileiros referência em transplante de células-tronco hematopoiéticas, com o objetivo de salientar a importância do estado nutricional e da composição corporal durante o tratamento, bem como as principais características relacionadas à avaliação nutricional do paciente. As intenções, ao se estabelecer o consenso, foram aprimorar e padronizar a terapia nutricional durante o transplante de células-tronco hematopoiéticas. O consenso foi aprovado pela Sociedade Brasileira de Transplante de Médula Óssea.

Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3 internal tandem duplication using the combination of induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases / Tratamento bem-sucedido de leucemia mieloide aguda recorrente após transplante com duplicação interna em tandem FLT3 usando combinação de indução por quimioterapia, infusão de linfócitos de doador, soferanib e azacitidina. Relato de três casos

ABSTRACT Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging. The report describes the outcomes of patients with FLT3 internal tandem duplication positive acute myeloid leukemia who relapsed after allogeneic hematopoietic stem cell transplantation and were treated with the combination of re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Three cases are described and all patients achieved prolonged complete remission with the combined therapy. The combination of induction chemotherapy followed by donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can be effective approaches in the treatment of post-hematopoietic stem cell transplant and relapsed FLT3 internal tandem duplication positive acute myeloid leukemia patients. This strategy should be further explored in the context of clinical trials.

RESUMO A leucemia mieloide aguda é uma doença neoplásica de células-tronco hematopoiéticas com alta morbimortalidade. A presença de mutações de duplicação em tandem de FLT3 leva a altas taxas de recorrência e a menor sobrevida global. Os pacientes com duplicação em tandem de FLT3 são normalmente tratados com transplante de células-tronco hematopoiéticas na primeira remissão completa. No entanto, a incidência de recidiva pós-transplante é considerável neste grupo de pacientes, e a conduta, nestes casos, é um desafio. O relato descreve os resultados do tratamento de pacientes com leucemia mieloide aguda positiva e duplicação em tandem de FLT3 que recidivaram depois do transplante alogênico de células-tronco hematopoiéticas e que foram tratados com combinação de quimioterapia de reindução, infusão de linfócitos de doador, sorafenib e azacitidina. São descritos três casos, e todos os pacientes apresentaram remissão completa prolongada com a terapia combinada. A combinação de quimioterapia de indução, seguida de infusão de linfócitos do doador, e a manutenção com azacitidina e sorafenib podem ser abordagens eficazes no tratamento da recorrência pós-transplante em pacientes com leucemia mieloide aguda e duplicação em tandem de FLT3. Essa estratégia deve ser mais explorada no contexto de ensaios clínicos.

Normalization of lymphocyte count after high ablative dose of I-131 in a patient with chronic lymphoid leukemia and secondary papillary carcinoma of the thyroid. Case report / Normalização da contagem de linfócitos após dose ablativa de I-131 em um paciente com leucemia linfóide crônica e carcinoma papilífero da tireóide. Relato de caso

The authors report the case of a 70-year-old male patient with chronic lymphoid leukemia who presented subsequently a papillary carcinoma of the thyroid with metastases to regional lymph nodes. The patient was treated with surgical thyroidectomy with regional and cervical lymph node excision and radioiodine therapy (I-131). The protocolar control scintigraphy 4 days after the radioactive dose showed I-131 uptake in both axillae and even in the inguinal regions. PET/CT showed faint FDG-F-18 uptake in one lymph node of the left axilla. An ultrasound guided fine needle biopsy of this lymph node identified by I-131 SPECT/CT and FDG-F-18 PET/CT revealed lymphoma cells and was negative for thyroid tissue and thyroglobulin content. The sequential blood counts done routinely after radiation treatment showed a marked fall until return to normal values of leucocytes and lymphocytes (absolute and relative), which were still normal in the last control 19 months after the radioiodine administration. Chest computed tomography showed a decrease in size of axillary and para-aortic lymph nodes. By immunohistochemistry, cells of the lymphoid B lineage decreased from 52% before radioiodine therapy to 5% after the procedure. The authors speculate about a possible sodium iodide symporter expression by the cells of this lymphoma, similar to some other non-thyroid tumors, such as breast cancer cells.

Os autores relatam o caso de um paciente de 70 anos com leucemia linfóide crônica que apresentou subsequentemente um carcinoma papilífero da tireóide com metástases para linfonodos regionais. O paciente foi tratado com tireoidectomia total cirúrgica com exérese de linfonodos regionais e cervicais e radioiodoterapia (I-131). A pesquisa de corpo inteiro protocolar de controle 4 dias após a dose radioativa mostrou captação de I-131 em ambas as axilas e mesmo nas regiões inguinais. PET/CT mostrou discreta captação de FDG-F-18 em um linfonodo da axila esquerda. A biópsia por agulha fina guiada por ultrassom deste linfonodo identificado por SPECT/CT com I-131 e PET/CT com FDG-F-18 revelou células linfomatosas e foi negativa para tecido tireoidiano e conteúdo de tireoglobulina. Os hemogramas sequenciais feitos rotineiramente após tratamento com radiações mostraram uma acentuada queda até retorno aos valores normais de leucócitos e de linfócitos (absolutos e relativos), que continuavam normais no último controle 19 meses após a administração do radioiodo. Tomografia computadorizada de tórax mostrou uma redução em tamanho de linfonodos axilares e para-aorticos. Por imunohistoquímica, as células da linhagem linfoide B decresceram de 52% antes da radioiodoterapia para 5% depois do procedimento. Os autores conjeturam sobre uma possível expressão de symporter de iodeto de sódio pelas células deste linfoma, à semelhança de outros tumores não tireoidianos, tais como células de câncer da mama.

Primary central nervous system lymphoma: what a neurologist/neurosurgeon should know? / Linfoma primário de sistema nervoso central: o que um neurologista/neurocirurgião deve saber?

Primary central nervous system lymphoma is a rare disease, with bad prognosis. Neurologists and neurosurgeons should be familiar with the diagnostic,and biologic features, as well as the initial management of patients. A correct approach to these patients is mandatory for a better outcome.

Linfoma primário do sistema nervoso central é uma doença rara, com prognóstico ruim. Neurologistas e neurocirurgiões devem estar familiarizados com os aspectos do diagnóstico, características biológicas e do manuseio inicial dos pacientes. A abordagem correta desses pacientes é essencial para obter melhores resultados.

Molecular biology of Philadelphia-negative myeloproliferative neoplasms

Myeloproliferative neoplasms are clonal diseases of hematopoietic stem cells characterized by myeloid hyperplasia and increased risk of developing acute myeloid leukemia. Myeloproliferative neoplasms are caused, as any other malignancy, by genetic defects that culminate in the neoplastic phenotype. In the past six years, since the identification of JAK2V617F, we have experienced a substantial increase in our knowledge about the genetic mechanisms involved in the genesis of myeloproliferative neoplasms. Mutations described in several genes have revealed a considerable degree of molecular homogeneity between different subtypes of myeloproliferative neoplasms. At the same time, the molecular differences between each subtype have become clearer. While mutations in several genes, such as JAK2, myeloproliferative leukemia (MPL) and LNK have been validated in functional assays or animal models as causative mutations, the roles of other recurring mutations in the development of disease, such as TET2 and ASXL1 remain to be elucidated. In this review we will examine the most prevalent recurring gene mutations found in myeloproliferative neoplasms and their molecular consequences.

Leucemia mieloide aguda: atualidade brasileira de diagnóstico e tratamento / Acute myeloid leukemia: update in diagnosis and treatment in Brazil

Objective: To identify how the Brazilian hematology centers treated and diagnosed cases of acute myeloid leukemia in 2009. Methods: An epidemiological observational multicenter study of 11 listed Brazilian centers that treat acute myeloid leukemia and perform bone marrow transplantation. Data were collected from clinical charts of patients with acute myeloid leukemia treated at the said centers between 2005 and 2009. The availability for immunophenotyping and cytogenetic tests was assessed. Results:During 2009, a total of 345 new cases of acute myeloid leukemia were diagnosed. Differences were noted in the tests performed between patients who initiated treatment at the center and those referred for treatment. Of the participating centers, 72% conducted some type of molecular study in acute myeloid leukemia upon diagnosis. Conclusion: Treatment for acute myeloid leukemia in Brazil shows significantly inferior results when compared to other centers worldwide.

Objetivo: Identificar como centros de hematologia brasileiros trataram e diagnosticaram os casos de leucemia mieloide aguda no ano de 2009. Métodos: Estudo epidemiológico, observacional, multicêntrico de 11 centros brasileiros cadastrados para tratamento de leucemia mieloide aguda e transplante de medula óssea. Os dados foram coletados a partir de prontuários de pacientes com leucemia mieloide aguda tratados nos centros citados entre os anos de 2005 e 2009. Foi avaliada a disponibilidade para realização de exames de imunofenotipagem e citogenética nos centros estudados. Resultados: Foram diagnosticados 345 casos novos de leucemia mieloide aguda no ano de 2009. Observaram-se diferenças na realização de exames entre pacientes que iniciaram o tratamento no centro em relação àqueles referenciados para tratamento. Dos centros participantes, 72% realizaram algum tipo de pesquisa molecular em leucemia mieloide aguda ao diagnóstico. Conclusão: O tratamento da leucemia mieloide aguda no Brasil apresenta resultados muito inferiores quando comparado a outros centros mundiais.

Uso de gemtuzumabe ozogamicina combinado com quimioterapia convencional em pacientes com leucemia mieloide aguda / Use of gemtuzumab ozogamycin combined with conventional chemotherapy in patients with acute myeloid leukemia

Objective: To analyze the outcome of patients treated with gemtuzumab ozogamycin combined with conventional therapy treated at Hospital Israelita Albert Einstein. Methods: 14 patients who had high risk features (secondary leukemia, unfavorable cytogenetics, and refractory disease) were treated with gemtuzumab ozogamycincombined with conventional therapy and their outcome was analysed by reviewing their medical records. Results: Overall response rate was 58%, with 43% achieving complete response, with a median followup of 11 months, event-free survival was 3 months. Eleven patients died, 6 of them due to refractory acute myeloid leukemia. Only four patients presented with grade 3 to 4 toxicities and only one patient had sinusoidal obstruction syndrome after bone marrow transplant. Conclusion: gemtuzumab ozogamycin combined with chemotherapy is a feasible treatment regimen in acute myeloid leukemia patients. However, further studies are necessary to clarify which subgroup of patients may benefit from this treatment.

Objetivo: Analisar a evolução de pacientes tratados com gemtuzumabe ozogamicina combinado à terapêutica convencional no Hospital Israelita Albert Einstein. Métodos: 14 pacientes que tinham alto risco (leucemia secundária, citogenética desfavorávele doença refratária) foram tratados com gentuzumabe ozogamicina associado à terapêutica convencional, e sua evolução foi analisada por meio de seus prontuários médicos. Resultados: A taxa total de resposta foi de 58%, com 43% chegando a resposta completa, em acompanhamento médio de 11 meses, e três meses com intervalo de sobrevivência livre. Foram a óbito 11 pacientes, 6 deles por leucemia mieloide aguda. Somente quatro pacientes apresentaram graus 3 a 4 de toxicidade e apenas um paciente teve síndrome de obstrução sinusoidal após transplante de medula. Conclusão: Gemtuzumabe ozogamicina associado à terapêutica quimioterápica convencional éum tratamento factível em pacientes com leucemia mieloide aguda. Contudo, novos estudos são necessários para esclarecer qual o subgrupo de pacientes que pode se beneficiar desse tratamento.

Manejo de eventos adversos da decitabina em pacientes com síndrome mielodisplásica / Management of decitabine toxicity in patients with myelodysplastic syndrome

O azanucleosídeo decitabina é aprovado para tratamento de pacientes com síndrome mielodisplásica de alto risco. Decitabina é droga relativamente bem tolerada quando comparada a esquemas de quimioterapia intensiva empregados em neoplasias mieloides, porém apresenta uma série de efeitos adversos, no qual se destaca a mielossupressão. A mielossupressão com decitabina depende do esquema posológico utilizado e tende a ser mais intensa nos primeiros ciclos de tratamento. Outros efeitos adversos de importância incluem mucosite, diarreia e hepatotoxicidade. Um conhecimento aprofundado sobre a toxicidade da decitabina e as melhores estratégias para seu manejo são necessários para se maximizar o benefício obtido com essa droga no tratamento da síndrome mielodisplásica.

Epidemiologia clinica da dor musculo-esqueletica / Clinical epidemiology of muscleskeletal pain

Varios estudos demonstram que as mulheres apresentam mais dor que os homens. Entretanto, os estudos sobre lombalgia e dor toracica nao sao conclusivos. Em casos de dores articulares e fibromialgia existe...

Genetica do cancer colorretal / Genetics of colorectal cancer

O cancer colorretal (CCR) e uma das neoplasias de maior importancia atualmente, tanto por sua prevalencia como por sua incidencia, correspondendo a...

Colorectal cancer screening

Colorectal cancer (CRC) is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps) that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening.