Search

Objective To analyze the effects of hospital cardiorespiratory physical therapy protocol on the functional capacity and quality of life of patients submitted to hematopoietic stem cell transplantation (HSCT). Methods From January to December 2019, bilateral dynamometry, Manovacuometry and Ventilometry, peak expiratory flow "Peak Flow", 6-min walk test (6MWT), SF-36 Quality of Life Questionnaire and Visual Analog Scale (VAS) were applied in patients who have undergone an allogeneic or autologous hematopoietic stem cell transplantation (HSCT), pre-conditioning (initial evaluation) and pre-discharge (final evaluation). The patients were submitted to an intervention protocol, consisting of aerobic training, muscle strengthening and respiratory muscle training, between the two assessments. Results 29 patients were enrolled in the study and 24 (83%) completed all procedure. Myeloablative and reduced intensity conditioning were performed in 89.6% and 10.4%, respectively; 17 (58%) patients have undergone an autologous HSCT; 10 (35%) identical related allogeneic HSCT, and 2 (7%) haploidentical allogeneic HSCT. The median number of interventions per patient was 3 (1–9). A decreasing in the right and left dynamometry (p ≤ 0.0001 and 0.002, respectively) and, also in the distance covered in the 6MWT (p = 0.004), was observed after HSCT. There was no significant difference in respiratory muscle strength, quality of life and fatigue sensation. Conclusion Cardiorespiratory rehabilitation can preserve functional capacity and quality of life.

O objetivo deste trabalho é descrever a experiência da implementação do Programa Mais Médicos Campineiro (PMMC) na cidade de Campinas, Estado de São Paulo, no período de abril de 2019 a abril de 2020, como resultado de política de saúde que adequou as necessidades do município à formação de médicos especialistas em Medicina da Família e Comunidade. Para tal, foram compilados registros de reuniões realizadas entre integrantes da Secretaria Municipal de Saúde e instituições de ensino superior do município e recuperada a trajetória percorrida pelos diversos atores envolvidos. A situação da atenção básica de saúde no município até 2019 foi analisada com detalhes, o que revelou dificuldades em fixar o médico nas Unidades de Saúde. Como solução optou-se pela instituição de programa de residência médica. Para preservar a manutenção do médico no programa, garantiu-se a sua vinculação à Estratégia de Saúde da Família, foram estabelecidas parcerias com instituições de saúde e foi planejado o financiamento que garantiu remuneração suficiente para atrair e manter profissionais à proposta. O processo seletivo de médicos residentes e preceptores foi amplamente discutido. Foi criado um programa pedagógico e estabelecida a gestão do programa. Foi verificado incremento da ocupação de vagas oferecida, demonstrando-se que por meio de política pública direcionada à formação de Médico da Família e Comunidade é possível alterar o panorama de ociosidade assim como a alta rotatividade de vagas em programas de residência médica em Campinas.

PURPOSE Isolated case reports mention the uptake of radiolabeled PSMA in lymphoma. However, it is not clear if the intensity of 68Ga-PSMA expression varies among different histological subtypes or if it correlates with 18F-FDG uptake. This study compared both tracers in patients with diverse lymphoma subtypes. METHODS Ten patients with biopsy-proven-lymphoma underwent 18F-FDG and 68Ga-PSMA-PET/CT (maximum time interval: 6 days). Lymphoma subtypes included Hodgkin's lymphoma (HL, three patients) and aggressive and indolent non-Hodgkin's lymphoma (NHL, seven patients). The intensity of PSMA uptake was classified visually as low, intermediate, or high, using blood pool, liver and parotid gland uptake as references. Maximum standardized-uptake value (SUVmax) of each affected site was measured in both sets of images. RESULTS FDG detected 59/59 involved sites in 10 patients and PSMA 47/59 sites in nine patients. PSMA uptake was generally low, regardless of the intensity of FDG uptake, but it was classified as intermediate in two patients. The median SUVmax varied from 2.0 (2.0-8.2) to 30.9 for FDG and from 1.7 (1.7-1.7) to 4.4 for PSMA, P < 0.0001. The primary lesion of one patient had a marked intralesional mismatch uptake pattern of the tracers, with areas of higher PSMA expression than FDG uptake, and vice-versa. A brain lesion was more easily identified with PSMA than with FDG images. CONCLUSION HL and several NHL subtypes may present PSMA uptake. The intensity of PSMA expression is generally lower than that of FDG uptake and seems to present less variation among the different histological subtypes of lymphomas.

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73-13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p = 0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674.

OBJECTIVES: Single nucleotide variants (SNVs) in vascular endothelial growth factor A (VEGFA) and VEGFA receptor (KDR) genes confer different inherited abilities in angiogenesis (AG) pathway. We aimed in the present study to evaluate influence of six VEGFA and four KDR SNVs in clinical features and survival of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: One hundred and sixty-eight DLBCL patients diagnosed between June 2009-September 2014 were enrolled in the study. Patients were homogeneously treated with R-CHOP. Genotypes were identified in genomic DNA by real-time polymerase chain reaction. RESULTS: Patients with VEGFA -634CC and +936CT or TT genotypes were at increased risk of showing grade III / IV toxicities and not achieving complete remission with treatment, and shorter event-free and overall survival were seen in patients with VEGFA -1154GA or AA genotype and VEGFA ATAGCC haplotype. CONCLUSION: Our data suggest that inherited abnormalities in AG’s gene modulate clinical features and prognosis of DLBCL patients homogeneously treated with R-CHOP.

Since December 2019 the world has been facing a newly identified coronavirus named SarsCov-2 which is the causative agent of COVID-19 that produces different symptoms. One of these symptoms is asymptomatic hypoxia, particularly in elderly patients. Despite the absence of signs of respiratory distress, many patients evolve to respiratory failure. The cause of this asymptomatic hypoxia remains unclear; therefore our goal was to evaluate the utility of peripheral oxygen measurements using oximetry in elderly patients with suspected COVID-19 and with no apparent signs of shortness of breath, during 10 consecutive days. Every elderly patient with suspected COVID-19 who sought medical care at one of the 12 Primary Health Unit (PHU) in the South-West area of Campinas, Sao Paulo State was enrolled in the 10-days monitoring report. Each patient had the levels of oxygen saturation (SpO2) monitored by pulse oximeter from the fifth to the tenth days after the onset of symptoms and, when possible, twice a day; 1297 patients (pts) were followed during the period from August 2020 to February 2021. A total of 9023 measurements were carried out using a SpO2 pulse oximeter. 163 (12.5%) cases were referred to the Emergency Room and 37 (3%) had to be hospitalized. The highest frequencies of symptoms occurred during the 6th and 8th day and included cough (16.8%), fatigue (12.8%), headache (9.7%), loss of taste and/or smell (6.8%). Among the patients who were hospitalized, 13 died (1%). The asymptomatic hypoxia remains unclear; however, the measurement of SpO2 levels appears to be a cheap and effective tool to be used as an alert system for further evaluation.

The study of the tumor microenvironment (TME) in follicular lymphoma (FL) has produced conflicting results due to assessment of limited TME subpopulations, and because of heterogeneous treatments among different cohorts. Also, important genetic determinants of immune response, such as single-nucleotide polymorphisms (SNPs), remain underexplored in this disease. We performed a detailed study of the TME in 169 FL biopsies using immunohistochemistry, encompassing lymphocytes, macrophages, and cytokines. We also genotyped 16 SNPs within key immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, and IL17F) in 159 patients. We tested associations between SNPs, clinicopathological features and TME composition, and proposed survival models in R-CHOP/R-CVP-treated patients. Presence of the IL12A rs568408 “A” allele associated with the follicular pattern of FOXP3+ cells. The IL12A AA haplotype included rs583911 and rs568408 and was an independent predictor of worse survival, together with the follicular patterns of T-cells (FOXP3+ and CD8+) and high IL-17F tumor levels. The patterns of CD3+, CD4+ and CD8+ cells, displayed as a principal component, also associated with survival. Hierarchical clustering of the TME proteins demonstrated a cluster that was associated with worse prognosis (tumors enriched in IL-17A, IL-17F, CD8, PD1, and Ki-67). The survival of FL patients who were treated in the rituximab era shows a strong dependence on TME signals, especially the T-cell infiltration patterns and IL-17F tumor levels. The presence of the AA haplotype of IL12A in the genome of FL patients is an additional prognostic factor that may modulate the composition of T-reg cells in this disease.

Agradecimentos: The authors would like to thank the Nuclear and Energy Research Institute (IPEN-CNEN), São Paulo, Brazil, for supplying the radiopharmaceuticals used in the present project (IPEN/UNICAMP agreement No. 01342000458/2017-15). The authors are grateful for the financial support from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), grant numbers 2009/54065-0 and 2018/00654-4 Abstract: Purpose: Quantifications in nuclear medicine are occasionally limited by the lack of standardization for defining volumes of interest (VOIs) on functional images. In the present article, we propose the use of computed tomography (CT)-based skeletal segmentation to determine anatomically the VOI in order to calculate quantitative parameters of fluorine 18 fluorodeoxyglucose (F-18-FDG) PET/CT images from patients with multiple myeloma. Methods: We evaluated 101 whole-body F-18-FDG PET/CTs of 58 patients with multiple myeloma. An initial subjective visual analysis of the PET images was used to classify the bone involvement as negative/mild, moderate, or marked. Then, a fully automated CT-based segmentation of the skeleton was performed on PET images. The maximum, mean, and SD of the standardized uptake values (SUVmax, SUVmean, and SDSUV) were calculated for bone tissue and compared with the visual analysis. Results: Forty-five (44.5%), 32 (31.7%), and 24 (23.8%) PET images were, respectively, classified as negative/mild, moderate, or marked bone involvement. All quantitative parameters were significantly related to the visual assessment of bone involvement. This association was stronger for the SUVmean [odds ratio (OR): 10.52 (95% confidence interval (CI), 5.68-19.48); P < 0.0001] and for the SDSUV [OR: 5.58 (95% CI, 3.31-9.42); P < 0.001) than for the SUVmax [OR: 1.01 (95% CI, 1.003-1.022); P = 0.003]. Conclusion: CT-based skeletal segmentation allows for automated and therefore reproducible calculation of PET quantitative parameters of bone involvement in patients with multiple myeloma. Using this method, the SUVmean and its respective SD correlated better with the visual analysis of F-18-FDG PET images than SUVmax. Its value in staging and evaluating therapy response needs to be evaluated FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP Fechado

Made available in DSpace on 2022-04-29T08:28:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-01 The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1,300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients. Hospital Israelita Albert Einstein Américas Oncologia AC Camargo Cancer Center Hospital das Clínicas da Faculdade de Medicina de Botucatu (HC-FMB) Instituto do Cancer de São Paulo (ICESP) Hemomed Hospital Municipal da Vila Santa Catarina Universidade de Campinas (UNICAMP) Grupo Oncoclínicas - CTO/CEON Hospital das Clínicas da Universidade Federal de Minas Gerais (HC UFMG) Centro de Cancer de Brasilia CETTRO Hospital Alemão Oswaldo Cruz Universidade Federal de São Paulo (Unifesp) Hospital Sírio Libanês Hospital de Clínicas de Porto Alegre (HPCA) Instituto Nacional do Cancer (INCA) Universidade Federal do Rio de Janeiro (UFRJ) Universidade Federal do Paraná (UFPR) FCM da Santa Casa de São Paulo Hospital Samaritano Higienópolis Hospital das Clínicas da Faculdade de Medicina de Botucatu (HC-FMB)

Lymphomas are a large, heterogeneous and infrequent group of neoplasms. Peripheral t-cell lymphomas (PTCL) is still rarer, and it makes up about 10-15% of lymphoid malignancies. Its prognosis is poor and remains a challenge. In April 2017, the first Brazilian collaborative effort was created to collect data from T-cell Lymphoma patients diagnosed in the five distinct macro-regions of Brazil. To better understand PTCL, according to the revised WHO-2017 classification, excluding Mycosis fungoides, Sézary syndrome, and chronic Lymphoproliferative disorders, all histological subtypes diagnosed from January 2015 to December 2022 will be enrolled. Tissue biopsied, immunophenotypic markers from consecutive patients at each site will be reviewed by panels of expert hematopathologists every year. So far, 381 cases were enrolled by 32 Brazilian centers, most of them are from the Southeast and South region. Twenty-two cases were not evaluable due to lack of complete data; hence, 359 were analyzed. The overall survival at 24-month was 52% (95% CI: 46-58%) and progression-free survival 37% (95% CI: 31-43%) with a median time of follow-up of 10 months (0.2-64). T-cell Brazil Project has many challenges to overcome, mainly due to its vast territory and its disparity. However, we already have another sixteen centers waiting for approval in their Ethics Committees. It was created a network around the country, mainly among the pathologists, with educational goals and exchange of experiences. It is crucial to obtain knowledge of local epidemiology to optimize resources, design clinical trials, and identify minority entities, contributing to increasing the quality o

Objective T-cell Brazil Project was designed as an ambispective data collection from January 2015 to December 2022 of previously untreated patients diagnosed with Peripheral T-cell lymphoma (PTCL) or NK/T-cell lymphoma according to the revised WHO 2017 classification in Brazil. The primary and secondary end points were 2-year overall survival (OS) and progression-free survival (PFS). Clinical, treatment and survival data were also correlated. Methodology Twenty centers got approved for the study from the local and national institutional review board and registered their cases only online. OS was calculated from diagnosis date until last seen or death date, whereas PFS until first event, progression / relapse, date of death or last seen. Kaplan-Meier method was applied and a Log-rank test to compare their curves. P-value less than 5% was considered. From a total of 416 patients with PTCL, 46 (11%) were diagnosed as AITL. Results The median age was 65 years (31-82), with 63% males, 94% had advanced-stage disease. All patients received 61% CHOEP, 28% CHOP and 11% CT without anthracycline. 20% of pts were consolidated with autologous transplant (HSCT). There were 19 (41%) deaths, 10 by lymphoma, 8 infections, 1 new neoplasia. With 8-mo median f/u (1-36), OS at 24-mo was 27% and 2-year PFS was 21%. As consolidation, OS was 71% HSCT group vs. 16% no HSCT (P= 0.06) and PFS was 71% vs. 8%, respectively (P= 0.01). Conclusion These analyses are preliminaries but show a poor outcome of AITL in our population. Most patients were treated with anthracycline-containing combination chemotherapy and just 20% received autologous HSCT. A dismal survival was shown for those who did not receive HSCT.

Objetivos Avaliar a efetividade e eficiencia de um protocolo de descontinuacao de inibidores de tirosina quinase (ITK) em tratamento no Sistema Unico de Saude (SUS) que incluiu uma fase de descalonamento de dose antes da interrupcao do tratamento. Materiais e metodos Estudo prospectivo, em andamento. Criterios de inclusao: LMC em fase cronica, em tratamento com ITK no minimo ha 3 anos, transcritos BCR-ABL tipicos, com resposta molecular profunda (RMP) por 2 anos (MR4.5) Exclusao: fase avancada previa ou atual, resistencia previa, mutacoes do ABL. Antes da suspensao do tratamento, foi realizado o descalonamento do ITK para 50% da dose atual por 6 meses. Durante a fase de descalonamento foi realizado monitoramento de PCR quantitativo para BCR-ABL (PCRq) mensal. Apos a descontinuacao do ITK o paciente foi seguido com avaliacoes clinicas, hemograma e PCRq a cada 4 semanas no primeiro semestre, a cada 2 meses no segundo semestre e no segundo ano e depois a cada 3 meses. A terapia foi reiniciada na perda de RMM (PCRq Resultados Entre setembro de 2020 e julho de 2021 foram triados 213 pacientes com LMC; 28 eram potencialmente elegiveis: 9 nao aceitaram participar; 19 assinaram o TCLE e um paciente teve falha de screening. A mediana de idade dos 18 participantes foi de 61.5 anos (35-86), 61% homens, 44.4% Sokal baixo risco ao diagnostico, 15.1% intermediario/alto; 81% com transcrito BCR-ABL do tipo b3a2; 78% estavam em uso de Imatinibe,11% Dasatinibe,5.5% Nilotinibe e 5.5% Bosutinibe. A mediana da duracao do tratamento com ITK ate o inicio do descalonamento foi de 136 meses (46-201); a duracao da RM 4.5 foi de 104, 5 meses (27-168); a mediana do tempo entre suspensao e perda de RMM foi de 2.5 meses (2-3). Oito pacientes perderam a RM4.5 durante a fase de descalonamento: destes, 2 perderam RMM, um na fase de descalonamento e outro na fase de descontinuacao. Status atual: sete pacientes estao na fase de descontinuacao, 8 na fase de descalonamento e 3 pacientes (16.6%) apresentaram recaida molecular. Nao houve nenhum evento adverso serio. Dois pacientes tiveram Covid-19 (leve) na fase de descalonamento. Discussao a descontinuacao tem sido proposta como estrategia terapeutica na pratica clinica nos pacientes com LMC com RM profunda sustentada. Nesses casos, a chance de sobrevida livre de remissao e de 50%. Poucos estudos avaliaram o efeito da retirada gradual do ITK antes da interrupcao. No estudo DESTINY, o descalonamento foi feito por 12 meses, e a sobrevida livre de terapia aos 36 meses foi de 72% nos pacientes com RM4.0. Nos resultados preliminares do nosso estudo, ainda em recrutamento de pacientes, com 10 meses de seguimento, observamos que das 3 recaidas, uma delas ocorreu na fase de descalonamento, em um paciente em uso de nilotinibe em segunda linha e outra em um paciente na segunda tentativa de descontinuacao, onde e esperado uma menor chance de sucesso. Conclusoes ate o momento o protocolo mostrou-se seguro, com resultados dentro do esperado na literatura. O seguimento a longo prazo e inclusao de novos pacientes nos permitira avaliar se a estrategia do descalonamento trara vantagem na sobrevida livre de terapia.

Many efforts have been made to standardize the interpretation of 18F-FDG PET/CT in multiple myeloma (MM) with qualitative visual analysis or with quantitative metabolic parameters using various methods for lesion segmentation of PET images. The aim of this study was to propose a quantitative method for bone and bone marrow evaluation of 18F-FDG PET/CT considering the extent and intensity of bone 18F-FDG uptake: Intensity of Bone Involvement (IBI). Whole body 18F-FDG PET/CT of 59 consecutive MM patients were evaluated. Compact bone tissue was segmented in PET images using a global threshold for HU of the registered CT image. A whole skeleton mask was created and the percentage of its volume with 18F-FDG uptake above hepatic uptake was calculated (Percentage of Bone Involvement - PBI). IBI was defined by multiplying PBI by mean SUV above hepatic uptake. IBI was compared with visual analysis performed by two experienced nuclear medicine physicians. IBI calculation was feasible in all images (range:0.00–1.35). Visual analysis categorized PET exams into three groups (negative/mild, moderate and marked bone involvement), that had different ranges of IBI (multi comparison analysis, p

Introduction: The incidence of grade 3–4 anemia was reported to be 3% with imatinib therapy for newly diagnosed chronic myeloid leukemia (CML) in the chronic phase (CP). However, there are few data regarding the causes and the development of anemia after long-term treatment. This study aimed to evaluate the incidence of anemia after at least two years of imatinib treatment of CML patients in the CP and to identify other contributing causes of anemia in this population. Patients and methods: We performed a retrospective analysis of 97 CML patients in the CP treated with imatinib for at least two years. We analyzed the hemoglobin (Hb) levels of CML patients at diagnosis, upon initiation of treatment with imatinib and after two years of imatinib treatment, and investigated other causes of anemia in this population. Results: Most of the patients presented Hb levels below the normal range (80.4%) after the second year of treatment, 17.9% grade 2 and 1.3% grade 3. In 13 cases (16.7%), anemia was attributed to resistance and in 13 cases (16.7%) the following causes were identified: iron deficiency (n = 5), hypothyroidism (n = 2), vitamin B12 deficiency (n = 3), acquired immune deficiency syndrome (AIDS) (n = 1), pulmonary tuberculosis (n = 1) and renal toxicity (n = 1). In 52 patients (66.6%), there were no other factors contributing to anemia, except imatinib treatment. Conclusion: Regular follow-up is required to identify the causes of anemia not related to CML or imatinib toxicity. The importance of investigating secondary causes of anemia should be emphasized, especially in patients with good adherence to treatment and satisfactory therapeutic response. Keywords: Chronic myeloid leukemia, Imatinib, Anemia, Adverse events

We analyzed the management and outcomes of pregnancies of patients with chronic myeloid leukemia at a single center over fifteen years. Among the 203 CML female patients, there were ten pregnancies in seven women, all of them not planned. In three cases, the chronic myeloid leukemia diagnosis was made during pregnancy. Five patients received tyrosine kinase inhibitors in the first weeks of pregnancy and the drug was interrupted until delivery. One patient lost complete cytogenetic response, and two patients lost the hematological response. A patient with a stable major molecular response had two successful pregnancies without loss of response. There were four premature births. There were no maternal adverse events, fetal malformation or death. All patients received Interferon-alpha during gestation, and two received hydroxyurea for a short period. Leukapheresis was performed in two patients for hyperleukocytosis control. One patient with sickle cell disease died from disease progression six months after delivery. Conclusions: The tyrosine kinase inhibitors ministration should be interrupted during pregnancy. Patients should be advised to achieve a stable and deep molecular response if they plan to conceive, to avoid the risk of disease progression. Keywords: Chronic myeloid leukemia, Pregnancy, Imatinib, Interferon-alpha, Hydroxyurea, Dasatinib

Aim: This study aimed to evaluate efficacy and safety of generic imatinib (IM) compared to branded imatinib (Glivec) in chronic myeloid leukemia. The primary end-point was the achievement of a major molecular response (MMR) at 12 months and safety. Secondary end-points included response evaluation, overall (OS), event-free survival (EFS) progression-free survival (PFS) and toxicity. Methods: Ambispective, multicenter, observational, non-inferiority study, in newly diagnosed Brazilian patients with chronic phase CML patients treated with IM in first line. The historic cohort consisted of CML patients treated with branded IM (Glivec) from January 2010 to December 2011 and the prospective cohort was treated with generics between January 2015 and December 2018. A total of 493 cases (214 Glivec and 279 Generic) from 10 centers were enrolled, and 393 (80%) patients were eligible for analysis (Glivec = 163; Generics = 230). EFS was measured from the start of treatment until loss of complete hematologic response, loss of major cytogenetic response, progression to accelerated or blast crisis, no response or insufficient response to study therapy, after a predefined period of time or death from any cause at any time during initial therapy or permanent discontinuation of IM by adverse events. Results: The median age was 45 and 49 years in Glivec and Generics groups, respectively (p = 0.056). Sokal score stratification in Glivec and generic groups, was respectively: low risk 50/50%; intermediate risk 49/38% and high risk 12/22% (p = 0.05). E14a2 (b3a2) frequency was 63% vs. 52% in Glivec and Generic group, respectively, and e13a2 (b2a2) 36% in both groups, e14a2+e13a2 were 1% vs. 12% (p = 0.005). There was no significant difference in gender, Eutos score and ECOG. The median time between diagnosis and treatment starting was 40 (0-169) and 28 (0-168) days (Glivec vs. Generics, respectively), p = 0.17. MMR rate at 12 months was 77/142 (54%) and 88/145 (61%) in Glivec and generics groups, respectively (p = 0.26). There were more failures in the generics group at 6 months (21% vs. 14%) (p = 0.03, respectively). There was no difference in grade 3-4 hematological and non-hematological toxicity in in the first 12 months. EFS at 24 months were higher in Glivec cohort and 76% vs. 53%, p < 0.0001, respectively), PFS and OS was not significantly different (respectively: 96% vs. 93%, p = 0.09 and 97% vs 96%, p = 0.41). The independent risk factors associated with inferior EFS were: generics use (HR = 1.78; 95%CI 1.06-2.99; p = 0.02) and High Sokal index (HR 2.25; 95%CI 1.38-3.67; p = 0.001). Conclusion: In the intention to treat analysis there was no significant difference in the primary end-point (MMR and safety at 12 months). The generics cohort presented more failures at 6 months compared to branded imatinib and inferior 24 month-EFS. There was no difference in the 24-month OS and PFS. The interpretation of the results should take into consideration the differences in CML management over the years.

Introdução: O papel da terapia de altas doses (TAD) seguida pelo transplante de células tronco periférico (TCTP) autólogo como consolidação é ainda muito discutido para os pacientes com Linfoma de células T periféricas (LCTP), ou seja, não há consenso atualmente sobre o gerenciamento ideal para o tratamento de primeira linha, principalmente devido ao viés de seleção de pacientes e das amostras pequenas nos estudos. Da mesma forma, com a disponibilidade de novos medicamentos, o uso TAD seguida de TCTP na consolidação ou salvamento deixou de serem as únicas opções disponíveis. Assim, nosso objetivo é descrever e verificar os resultados desses procedimentos e compreender o papel da TAD seguida de TCTP nestes pacientes. Métodos: Entre janeiro de 2015 e julho de 2021, 414 pacientes foram registrados por 34 centros brasileiros; destes 374 tinha informação disponível das terapias usadas. Um total de 70 (18.5%) casos foi submetido ao TAD seguido TCTP e este grupo é o foco deste estudo. Sobrevida global (SG) foi calculada a partir da data do diagnóstico até a data da última visita ou data de óbito. A sobrevida livre de progressão (SLP) da data do diagnóstico até data do 1° evento ou última consulta. Para o grupo de salvamento (TCTP-S) foi calculado a SLP considerando a data do TCTP até a data da última consulta ou 1° evento, sendo o evento progressão ou morte. Resultados: A mediana de idade dos pacientes transplantados foi de 51 anos (20-75), 37 (53%) sexo masculino, 20% teve performance status > 1; 60% apresentaram sintomas B e 67% teve algum sintoma relacionado à doença. 73% apresentou estadio III/IV; 16% dos casos tinham envolvimento extranodal > 1 e 17% tinham doença com bulky; Os subtipos mais frequentes foram 39% Linfoma de células T periféricas não especificado; 28% Linfoma de grandes células T anaplásicas, ALK- e 17% Linfoma angioimunoblástico. O grupo TCTP-C teve 54 pacientes e o status da doença antes do procedimento foi 50 (92,5%) casos com RC e 4 RP (7,5%); o TCTP-S foi realizado em 18 casos e 2 pacientes foram transplantados em ambos os momentos. Em relação ao tipo de TCTP, na consolidação, foram realizados 48 autólogos e 6 alogênicos, enquanto no salvamento foram 13 autólogos e 5 alogênicos. Após uma mediana de seguimento de 23 meses (4-77) para o grupo TCTP-C e 25 meses (6-43) para TCTP-S, a SG do grupo com TCTP-C foi de 81% (IC 95% 69-93%) e 71% (IC 95% 24-88%) para o TCTP-S, P = 0.16; A SLP foi de 61% (IC 95% 45-77%) e 7% (IC 95% 0-19%), respectivamente, p < 0,0001. Analisando o grupo TCTP-S, a resposta após o TCTP foi 4 (22%) RC, 1 (5,5%) RP, 3 (16,5%) doença estável, 5 (28%) progressão e 5 (28%) morreram. A mediana de seguimento foi 10 meses (1-23), e a SG-S foi 54% e 56% SLP-S em dois anos. Conclusões: De acordo com os dados da literatura, o TCTP pode indicar um controle em longo prazo para o LCTP alcançando uma estabilização após 5 anos e nossos dados apresentam curvas de 3 anos para o grupo consolidação, sugerindo que este procedimento é uma boa opção para melhorar os resultados finais. (Número do Clinical trials: NCT03207789).

Background There is evidence to consider that the tumor microenvironment (TME) composition associates with antitumor immune response, and may predict the outcome of various non-Hodgkin lymphoma subtypes. However, in the case of mantle cell lymphoma (MCL), a rare and aggressive disease, there is lacking a detailed study of the TME components, as well as an integrative approach among them in patients’ samples. Also, from the genetic point of view, it is known that single nucleotide variants (SNVs) in immune-response genes are among important regulators of immunity. At present, it is uncertain whether SNVs in candidate immune-response genes and the TME composition are able to alter the prognosis in MCL. Methods We assessed a detailed TME composition in 88 MCL biopsies using immunohistochemistry, which was automatically analyzed by pixel counting (Aperio system). We also genotyped SNVs located in candidate immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, IL17F) in 95 MCL patients. We tested whether the SNVs could modulate the respective protein expression and TME composition in the tumor compartment. Finally, we proposed survival models in rituximab-treated patients, considering immunohistochemical and SNV models. Results High FOXP3/CD3 ratios (p = 0.001), high IL17A levels (p = 0.003) and low IL2 levels (p = 0.03) were individual immunohistochemical predictors of poorer survival. A principal component, comprising high quantities of macrophages and high Ki-67 index, also worsened outcome (p = 0.02). In the SNV model, the CC haplotype of IL10 (p IL2 rs2069762 (p = 0.02) and the AA+AG genotypes of TGFBR2 rs3087465 (p TGFB1 rs6957 associated with lower tumor TGFβ levels (p = 0.03) and less CD163+ macrophages (p = 0.01), but did not modulate patients’ survival. Conclusions Our results indicate that the TME composition has relevant biological roles in MCL. In this setting, immunohistochemical detection of T-reg cells, IL17A and IL2, coupled with SNV genotyping in IL10, TGFBR2 and IL2, may represent novel prognostic factors in this disease, following future validations.

Made available in DSpace on 2022-04-29T08:45:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 This observational, multicenter study aimed to report the clinical evolution of COVID-19 in patients with chronic myeloid leukemia in Latin America. A total of 92 patients presented with COVID-19 between March and December 2020, 26% of whom were severe or critical. The median age at COVID-19 diagnosis was 48 years (22–79 years), 32% were 60 years or older, and 61% were male. Thirty-nine patients presented with at least one comorbidity (42.3%). Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. There was one case of reinfection. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; p = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (100, 89, 50, and 33%, respectively; p < 0.001). Hematology and Hemotherapy Center University of Campinas Hospital Nacional Edgardo Rebagliati Martins Centro Médico Nacional Siglo XXI IMSS JM Ramos Mejia CABA Hospital de Transplantes Euryclides de Jesus Zerbini Faculdade de Medicina da Universidade Federal do Ceará Hospital Universitário Walter Cantídio Complexo Hospital de Clínicas–Universidade Federal do Paraná Laboratory of Medical Investigation in Pathogenesis and targeted therapy in Onco-Immuno-Hematology (LIM/31) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Hospital de Valdivia Bueras Centro de Pesquisas Oncológicas Hospital dos Fornecedores de Cana de Piracicaba Hospital AC Camargo Cancer Center Hospital Universitário Antonio Pedro Universidade Federal Fluminense Hospitalization & Clinical Research Center Fundaleu Hospital Jorge Valente Hospital Santa Casa de Misericordia de Maceió Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto University of São Paulo Hospital Santa Marcelina São Paulo State University UNESP Medical School Campus de Botucatu Hemorio São Paulo State University UNESP Medical School Campus de Botucatu

Background This study aimed to identify the use of alcohol in adult men and to verify the association with socioeconomic, demographic and mental disorders. Methods A cross-sectional analytical study was carried out on adults aged 20 to 59 years old in the city of Piracicaba registered in the Family Health Units (FHU) in 2018. The pattern of alcohol use was investigated in the population through the application of the AUDIT (The Alcohol Use Disorders Identification Test) instrument. Through the modified socioeconomic questionnaire by Meneghim et al, socioeconomic and demographic factors were investigated. The brief investigation of the main mental disorders: major depressive episode and generalized anxiety disorder, was carried out with the Mini International Neuropsychiatric Interview (MINI). The sample was selected “post-hoc” considering the sample, with a significance level of 5% and test power above 80% (β = 0.20) (effect size = 0, 33). After contacting the FHU and selecting participants, the interviews were conducted over the phone in one step. The eligible sample had 227 participants. After descriptive analyzes, variables with p-value Results There was a high prevalence of alcohol consumption, 26.9%. The AUDIT score increased with age (RM: 1.02; 95% CI: 0.99-1.03). Protestants and evangelicals had an average AUDIT score lower than other religions (RM: 1.78; 95% CI: 1.14-2.79). People with mental disorders have an average AUDIT score higher than those without disorders (RM: 2.30; 95% CI: 1.28-4.11). Conclusions It is concluded that alcohol in the adult male population was prevalent, increases with age, and religion has a protective effect. We highlight the importance of the USF in the development of strategies that investigate the conditions of its population, as well as the discussion and approach of interventions Key messages The adult male population is more vulnerable to alcohol use and its consequences. Thus, early detection and the search for associated factors is necessary to avoid possible damage to men's health. The application of the Mini International Neuropsychiatric Interview instrument, can act preventively and with early interventions in mental disorders and in association with alcohol use.

Introduction: Ruxolitinib has been approved for the treatment of myelofibrosis (MF). In this study, we present safety and efficacy findings from an analysis of 104 patients with intermediate- and high-risk MF in a Brazilian cohort of the JUMP study who received treatment with ruxolitinib. Methods: JUMP is a single-arm, open-label, phase IIIb, expanded-access study. The primary endpoint was to evaluate the safety and tolerability (frequency, duration, and severity of adverse events [AEs]) of ruxolitinib. Results: All of the 104 patients received the treatment. Median duration of exposure was 35.8 months. The most common hematologic AEs were anemia (57.7), thrombocytopenia (38.5%), neutropenia (11.5%), and leukopenia (9.6%). Second malignancies (all grades) occurred in 19.2% of patients (n = 20). Serious AEs were reported in 62.5% of patients (n = 65). The proportions of patients with ≥50% reduction from baseline in palpable spleen length at weeks 24 and 48 were 62.7% and 69.2%, respectively. The mean change from the baseline in the Functional Assessment of Cancer Therapy (FACT)-Lymphoma total score was 10.8 [15.6%] at week 4, 12.6 [14.1%] at week 24, and 12.2 [14.3%] at week 48. The mean change from the baseline for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale was 3.9 [42.8%] at week 4, 4.9 [29.9%] at week 24, and 4.7 [28%] at week 48. At week 48, the estimated progression-free survival, leukemia-free survival, and overall survival probabilities were 91%, 91% and 93%, respectively Overall, 21 deaths were observed in the present study. Conclusion: Findings from this study suggest that ruxolitinib could be evaluated as a standard-of-care treatment for the MF population in need of a viable treatment option. NCT01493414 Keywords: Ruxolitinib, Myelofibrosis, JUMP, Brazil

Summary Background Extranodal natural killer (NK) T-cell lymphoma (ENKTL) is a unique clinicopathological entity, typically associated with poor survival outcomes. Most published data have come from east Asian study groups, with little information available from international cohorts. The effects of treatment advances on routine clinical practice across continental territories has not been clear. We aimed to improve understanding of the clinical characteristics and outcomes of patients with ENKTL. Methods We did a substudy of patients with ENKTL from the T-cell Project, a global prospective cohort study. The T-cell Project registered consecutively diagnosed adults (>18 years) with newly diagnosed, untreated mature T-cell or NK lymphomas (WHO 2001 or 2008 classifications) from 74 centres in 13 countries (in Asia, Europe, North America, and South America). In total, 1695 patients with mature T-cell or NK lymphomas were enrolled between Oct 12, 2006 and Feb 28, 2018 in the T-cell Project. The first patient with ENKTL was enrolled on Feb 15, 2007, and the last on May 26, 2017. Data on baseline characteristics, first-line treatment, treatment response, and survival outcomes were recorded in a central database (locked March 30, 2019). The primary outcome was 5-year overall survival. The T-cell Project is registered on ClinicalTrials.gov , NCT01142674 . Findings 166 patients were diagnosed with ENKTL, comprising 11% of 1553 eligible registered cases and distributed across 40 participating centres in four continents. At a median follow-up of 44 months (IQR 20–61), overall survival at 5 years was 54% (95% CI 44–63) in patients with nasal disease (n=98) and 34% (27–46) in patients with extranasal disease (n=68). Interpretation To our knowledge, this study presents the largest international cohort of patients with ENKTL. We describe a clinically significant improvement in the survival of patients with ENKTL treated in routine clinical practice over the past decade, likely to be attributable to the increasing use of treatment protocols specific for ENKTL. Funding The Fondazione Cassa di Risparmio di Modena, the Associazione Angela Serra per la Ricerca sul Cancro, the Fondazione Italiana Linfomi, Allos Therapeutics, Spectrum Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro, and the National Cancer Institute at the National Institutes of Health.

Summary Background In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. Methods LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II–IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT00722137 , and is closed to new participants with follow-up completed. Findings Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1–94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51–0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. Interpretations Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma. Funding Janssen Research & Development.

Objective: Follicular and mantle cell lymphoma are low-grade B-cell malignancies that lack good responses to chemoimmunotherapy. This study aimed to assess retrospectively clinicopathological features and to determine independent prognostic factors for follicular and mantle cell lymphoma patients treated at two Brazilian medical centers: the Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (Unicamp), a public university hospital, and AC. Camargo Cancer Center, a specialized cancer center. Methods: Two hundred and twenty-seven follicular and 112 mantle cell lymphoma cases were diagnosed between 1999 and 2016. Archived paraffin blocks were retrieved and reviewed. Corresponding demographics and clinical data were recovered from medical charts. Outcome analyses considered both overall and event-free survival. Results: For follicular lymphoma treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) and R-CVP (rituximab, cyclophosphamide, vincristine sulfate, prednisone) regimens, both B-symptoms (p-value

Objective: To investigate, in a large prospective multicenter study, whether 2-[18F]-fluoro-2-deoxy-d-glucose-positron emission tomography is sufficiently accurate to identify clinically important bone marrow involvement by Hodgkin's lymphoma to replace routine bone marrow biopsy in a developing tropical country. Methods: Patients newly diagnosed with Hodgkin's lymphoma were recruited from six cancer centers in Brazil. All were staged by the results of positron emission tomography/computed tomography that were centrally reviewed and by iliac crest bone marrow biopsy. Patients were classified as having marrow disease if they had lymphoma identified by marrow biopsy histology or had focal 2-[18F]-fluoro-2-deoxy-d-glucose marrow uptake that resolved following chemotherapy. Results: A total of 246 participants were recruited from six different centers and 62 (25.2%) were judged to have Hodgkin's lymphoma in the bone marrow. Positron emission tomography and biopsies were concordant in 206 patients (83%). Positron emission tomography correctly identified marrow disease in 59/62 patients (95.1%) and marrow biopsy in 25/62 patients (40.3%). In 22/62 (35.4%) patients, the two techniques were concordant in the diagnosis of marrow involvement. Of the forty discordant results, positron emission tomography found bone marrow involvement in 37 patients, upstaging 22 to stage IV and having an impact on therapeutic decision in nine cases given their reallocation from early to advanced stage. Three false negative positron emission tomography results were obtained with bone marrow biopsy giving positive findings. All three cases were classified as stage IV regardless of bone marrow findings implying no modification in the clinical management. The sensitivity, specificity and accuracy of positron emission tomography for detecting bone marrow disease were 95%, 100% and 98% and for bone marrow biopsy they were 40%, 100% and 84%, respectively. Conclusion: We conclude that positron emission tomography can replace marrow biopsy in Brazilian patients with Hodgkin's lymphoma without compromising clinical management. Keywords: Hodgkin's lymphoma, FDG-PET, Positron-emission tomography, Bone marrow biopsy, Lymphoma staging

Study Objective This study aimed to describe a novel access route to the sacrospinous ligament and the coccygeal muscle. The overarching goal was to show our team's standard systematization to this technique and state it's safety in low parametric injuries. Design Video description of the novel technique with clear illustrations of each step. Setting N/A. Patients or Participants The surgery was performed in a 27-year-old woman who suffered from deep endometriosis in the pelvic floor. Her diagnosis was performed through physical examination, with innervation compression symptoms, ultrasound and MRI imaging techniques. Interventions After the identification and release of the central structures, we proceed to the lateral approach with the isolation of the internal iliac artery, which should be medially tractioned, enabling the identification of the bifurcation of the common iliac vein into the internal and external iliac vein. We then start the systematization of the approach with the dissection of the avascular space between the "V" shape formed by the umbilical artery and uterine artery, subsequently heading towards the sacrum. Next, we identify the rectovaginal fascia, being the first structure to be identified, extending from the rectovaginal space to the tendon arch. Behind this structure, we can find the coccygeal muscle and the sacrospinous ligament extending from the sciatic spine towards the sacrococcyx. Measurements and Main Results We conclude the systematization of the pelvic floor approach being able to safely perform the resection of the endometriotic nodules with intact innervation, tension-free muscles and greater damage control. Conclusion In summary this novel approach to the pelvic floor is thought to be a simpler and less risky alternative to treat low parametric injuries afflicting the sacrospinous ligament and the coccygeal muscle.