Academic literature on the topic 'Hematologic neoplasm'

Liquid profiling uses circulating tumor DNA (ctDNA) for minimal invasive tumor mutational profiling from peripheral blood. The presence of somatic mutations in peripheral blood cells without further evidence of a hematologic neoplasm defines clonal hematopoiesis of indeterminate potential (CHIP). CHIP-mutations can be found in the cell-free DNA (cfDNA) of plasma, are a potential cause of false positive results in liquid profiling, and thus limit its usage in screening settings. Various strategies are in place to mitigate the effect of CHIP on the performance of ctDNA assays, but the detection of CHIP also represents a clinically significant incidental finding. The sequelae of CHIP comprise the risk of progression to a hematologic neoplasm including therapy-related myeloid neoplasms. While the hematological risk increases with the co-occurrence of unexplained blood count abnormalities, a number of non-hematologic diseases have independently been associated with CHIP. In particular, CHIP represents a major risk factor for cardiovascular disease such as atherosclerosis or heart failure. The management of CHIP requires an interdisciplinary setting and represents a new topic in the field of cardio-oncology. In the future, the information on CHIP may be taken into account for personalized therapy of cancer patients.

Abstract Background With the increasing accessibility of next-generation sequencing (NGS), many institutions are incorporating routine mutational profiling to assist in the evaluation of patients with a variety of hematologic disorders, including cytopenias. Such testing can be helpful in distinguishing neoplastic causes of cytopenias from others. Mutation profiling of peripheral blood is a particularly attractive option because of its potential application as a minimally invasive screen for hematologic malignancies, particularly myeloid neoplasms. However, it is not entirely clear how such molecular data can inform hematology practice as there is limited data on the clinical value of routine NGS testing in cytopenic patients. Here we report the clinical utility of peripheral blood screening by targeted NGS testing in a large institutional cohort of patients with cytopenias. Methods After institutional review board approval, we identified all patients presenting with peripheral blood cytopenias over a 30-month period (January 2015 - June 2017) to the Adult Hematology Clinic at Dana-Farber/Brigham and Women's Cancer Center (n=1491). Of these, 244 patients (median age: 66, range: 22-93) underwent testing of a peripheral blood specimen using a custom 95-gene, amplicon-based sequencing panel (Rapid Heme Panel, Kluk et al., 2016) surveying genes recurrently mutated in hematologic malignancies (Table 1). In addition, these patients also received a complete hematologic work-up to determine the cause for the cytopenia(s). All patients with a known history of a hematologic malignancy were excluded. Results Overall, 60 (25%) patients had a pathogenic somatic mutation in at least one of the 95 genes studied (Figure 1). An underlying hematologic malignancy was identified in 26 (44%) of these patients at the time of presentation, most commonly a myeloid neoplasm (19/26; 73%); 11 (18%) had a non-neoplastic etiology of the cytopenia(s); and 23 (38%) had unexplained cytopenia(s) following complete work-up. The most frequently mutated genes in patients with unexplained cytopenias were TET2, SF3B1 and SRSF2. Of the 184 (75%) patients without a pathogenic somatic mutation, 15 (8%) of these patients were found to have an underlying hematologic malignancy at the time of presentation, most commonly a lymphoid neoplasm (11/15; 73%); 84 (46%) had a non-neoplastic etiology of the cytopenia(s); and 85 (46%) had unexplained cytopenia(s) following complete work-up. With a median follow-up of 22 months, two patients with non-clonal unexplained cytopenias went on to develop MDS and splenic marginal zone lymphoma, respectively. Overall, the presence of a pathogenic mutation was strongly associated with the diagnosis of a myeloid neoplasm (RR 11.6, 95% CI 4.5-29.8). Conversely, if no pathogenic mutation were identified, the likelihood of developing a myeloid neoplasm in 2 years was low (5/184; 2.7%). To further investigate the diagnostic utility of peripheral blood mutational profiling as a screening test in predicting the presence of a myeloid neoplasm on bone marrow biopsy, we studied its diagnostic characteristics using bone marrow biopsy diagnosis within a 6-month interval as the gold standard (n=57). The absence of a pathogenic mutation in peripheral blood was highly predictive of absence of a myeloid neoplasm on bone marrow biopsy (NPV 94%, 95% CI 84-99%). The presence of specific mutations in spliceosome genes (SF3B1, SRSF2, U2AF1) and co-mutation patterns involving DNMT3A, TET2 and ASXL1 genes and other genes were predictive of a myeloid neoplasm with positive predictive values of 75% (95% CI 41-93%) and 70% (95% CI 41-88%) respectively. Finally, larger clone sizes (≥20%) and higher numbers of mutations (≥2) were also predictive of a myeloid neoplasm (PPV: 80%, 95% CI 60-90% and 75%, 95% CI 49-90%, respectively). Conclusions In conclusion, mutation profiling of peripheral blood is a valuable minimally invasive test in the diagnostic work-up of the cytopenic patient. After a complete hematologic work-up and in the absence of a pathogenic somatic mutation, the likelihood of developing a myeloid neoplasm in 2 years is very low. Also, the lack of a pathogenic mutation in peripheral blood is highly predictive of the absence of a myeloid neoplasm on a bone marrow biopsy. Finally, certain molecular features (number and type of mutations, clone size) are predictive of a myeloid neoplasm. Disclosures Kim: LabCorp, Inc.: Consultancy; Papgene, Inc: Consultancy; Aushon Biosciences: Consultancy.

Abstract Context.—In the diagnosis of lymphomas and leukemias, flow cytometry has been considered an essential addition to morphology and immunohistochemistry. The interpretation of immunophenotyping results by flow cytometry involves pattern recognition of different hematologic neoplasms that may have similar immunologic marker profiles. An important factor that creates difficulty in the interpretation process is the lack of consistency in marker expression for a particular neoplasm. For this reason, a definitive diagnostic pattern is usually not available for each specific neoplasm. Consequently, there is a need for decision support tools to assist pathology trainees in learning flow cytometric diagnosis of leukemia and lymphoma. Objective.—Development of a Web-enabled relational database integrated with decision-making tools for teaching flow cytometric diagnosis of hematologic neoplasms. Design.—This database has a knowledge base containing patterns of 44 markers for 37 hematologic neoplasms. We have obtained immunophenotyping data published in the scientific literature and incorporated them into a mathematical algorithm that is integrated to the database for differential diagnostic purposes. The algorithm takes into account the incidence of positive and negative expression of each marker for each disorder. Results.—Validation of this algorithm was performed using 92 clinical cases accumulated from 2 different medical centers. The database also incorporates the latest World Health Organization classification for hematologic neoplasms. Conclusions.—The algorithm developed in this database shows significant improvement in diagnostic accuracy over our previous database prototype. This Web-based database is proposed to be a useful public resource for teaching pathology trainees flow cytometric diagnosis.

Abstract Background: The recent advances in molecular techniques and the adaptation of next generation sequencing (NGS) in routine clinical testing increased our ability to use molecular approaches in the diagnosis and classification of most hematologic diseases. Bone marrow aspiration and biopsy remains necessary for initial confirmation of diagnosis of neoplastic processes in bone marrow, but significant literature suggests that screening or monitoring patients by testing peripheral bloodcfDNAmight be a reliable alternative to marrow biopsy and might reduce the need for a painful bone marrow procedure. Here we report the results of routine clinical testing ofcfDNAthat is ordered by practicing hematologist in the context of the presence or the suspicion of the presence of hematologic neoplasm. Methods: A total of 227 peripheral blood samples were submitted for screeningcfDNAfor mutations in a 54 gene focusedMyeloidpanel using NGS sequencing. DNA was extracted from plasma usingNucliSenSEasyMAGautomated platform and then assayed using theTruSightMyeloid Sequencing Panel (Illumina; San Diego, CA) with an average sequencing depth of 10,000X. The average age patients was 71 (18-96) years. The reason for submitting samples wasruling out MDS in 199 and ruling out AML or other hematologic neoplasms in 28 samples. Of these samples, 12 patients had a follow up testing of bone marrow aspiration sample. Results: Of the 227 tested samples (Figure 1), 126 (55%) showed no evidence of mutation in any of the tested genes. Based on our previous data (see ASH abstract by Albitar et al, 2016), this suggested that MDS can be ruled out in these patients and bone marrow biopsy could be avoided and not recommended. In contrast, 101 (45%) had mutations in one or more genes. Twenty-nine (~12.8%) contained a mutation in a single gene with variant allele frequency (VAF) <20% in one gene and were considered not diagnostic for the presence of clinically significant hematologic neoplasm, but follow up was recommended. Of these patients, one had a mutation in JAK2 at VAF of 6% and a second had a mutation in CALR gene at VAF of 7%, which most likely suggest the presence of early evolvingmyeloproliferativeneoplasms. Seventy-four patients (33%) had mutations in two or more genes or in one gene but with VAF≥20% and considered diagnostic for the presence of hematologic neoplasm and bone marrow morphologic evaluation was recommended. The most commonly mutated gene in these patents was TET2, detected in 30 samples, of which 8 also showed a second mutation in TET2, followed by ASXL1, and DNMT3A mutated in 24 and 26 samples, respectively. Samples containing a TET2 mutation were more likely to have a second mutation in TET2 or another gene, in contrast other genes that were frequently mutated did not show this trend (see Figure). TP53 gene was mutated in 16 samples, 7 of which as a single abnormality with VAF <20% therefore was reported as of unknown significance and recommended ruling out neoplasms in hematologic (lymphoid and myeloid) as well as solid tumors. SF3B1 gene mutations were detected in 19 samples and recommended ruling out refractory anemia with ringsideroblasts(RARS). Despite the small sampling (12 samples), follow up usingcfDNAtesting reliably recapitulated original bone marrow Biopsy's findings. In one patient, additionalsubcloneswere detected incfDNAthat were not detected in the bone marrow aspirate. Conclusions:cfDNAtesting is reliable approach to screen for the presence of Hematologic neoplasm and potentially could avoid the need for bone marrow biopsy in almost half the patients expected to have MDS or otherhematopoeticneoplasms. Positive diagnosis can be confirmed in additional 45% of patients and only 12.8% of patients will be reported with questionable results. Except for those with TP53 mutations, the rest of the 12.8% cases can be classified as Clonal Hematopoiesis of Indeterminate Potential (CHIP). While bone marrow is still the gold standard, our real world experience shows liquid biopsies can be sensitive and non-invasive approach to rule out MDS or other hematological diseases. Disclosures Funari: NeoGenomics Laboratories: Employment. Ma:Neogenomics Laboratories: Employment. Thangavelu:Neogenomics Laboratories: Employment. De Dios:Neogenomics Laboratories: Employment. Albitar:Neogenomics Laboratories: Employment, Equity Ownership.

The purpose of the study was to analyze the cumulative incidence of hematological neoplasia and evaluate the dynamics of this in different regions of Cherkasy oblast in 1980, 1989, 2001, 2014 yy. Materials and methods. The epidemiological parameters of hematological neoplasms in the radiation-contaminated (RC), chemically contaminated (CC), radiation and chemically contaminated (RCC), conditionally clean (CNC) regions of Cherkassy oblast (CO) in 1980, 1989, 2001, 2014 yy. were analyzed. Classification of CO territories to the RC, CC, RCC, CNC regions was conducted based on reports of the dosimetry certification of all settlements of Ukraine after the Chernobyl accident and the results of determination of the level of chemical contamination by the sanitary and epidemiological service during 1980-2014 yy. Results. It was determined, that, at the limit of statistical significant (p = 0.057), on the RC territory of CO in 2001 year the relative risk for the cumulative incidence of hematologic neoplasia was on 1.41 times higher (18,682 (95 % confidence interval (CI) = 14,426 – 16,879) against 13,187 (95 % CI = 9,495 – 16,879)), compared with CNC region. In addition, in the RC territory from 1989 to 2001 year the increasing at 9,342 times (1,999 (95% CI = 0.69–3.305) versus 18,682 (95% CI = 14.426 – 16.879)) of cumulative incidence of the hematopoietic and lymphoid systems neoplasm was detected. It is proved, that in the CNC region from 2001 to 2014 year at 1,791 times (13,187 (95% CI = 9.495 – 16.879) versus 23,619 (95% CI = 18.412 – 28.826)) higher level of the cumulative incidence of hematologic neoplasia was observed. Conclusions. In the CO, which was polluted by the radiation factor because of the Chernobyl nuclear power plant accident, 5 years after that, in 2001 was detected the increasing of the relative risk of hematologic neoplasia, compared to that on the CNC region. In addition, on the RC territory from 1989 to 2001 year the increasing at 9,342 times of the incidence of hematopoietic and lymphoid system tumors was observed. This is evidence of pro-leukemic effects of ionization radiation and, probably, the increase in the diagnostic potential of the hematological service of the CO.

Abstract Background: Secondary tumors has been described in a variety of patients with either hematologic malignancies or solid neoplasm, and most of the time is related to previous chemotherapy and radiation therapy exposure, but little is found in the literature about synchronous or metachronous neoplasm that can be found in patient with a newly diagnosis of hematologic malignancy; we report 45 cases, presented in a single institution from 2007 to present. Methods: A retrospective review of records using our tumor registry data, from patient with hematologic malignancies at John H. Stroger Hospital of Cook County, was performed and 45 patients with either synchronous or metachronous neoplasm were identified. Results: Lung cancer was the most common malignancy representing 22.2%, Colorectal cancer 20%, Prostate cancer 17.7%, Breast cancer 11.1%, Urothelial cancer (Kidney and Bladder) 8.8%, Myelodisplastic syndrome, Pancreatic cancer, Thyroid cancer, Non-Hodgking lymphoma, Acute Myeloide Leukemia, Vulvar cancer, Testicular cancer and Skin Cancers 2.2% each one respectively. Results: We found that in our heterogeneous population of patient with hematologic malignancies, the incidence of synchronous or metachronous neoplasm practically follows a very similar pattern of the general population, despite that many of this patients have been exposed to chemotherapy and radiation therapy. Disclosures No relevant conflicts of interest to declare.

Hematopoietic stem cell aging, through the acquisition of somatic mutations, gives rise to clonal hematopoiesis (CH). While a high prevalence of CH has been described in otherwise healthy older adults, CH confers an increased risk of both hematologic and non-hematologic diseases. Classification of CH into clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS) further describes this neoplastic myeloid precursor state and stratifies individuals at risk of developing clinically significant complications. The sequential acquisition of driver mutations, such as DNMT3A, TET2, and ASXL1, provide a selective advantage and lead to clonal expansion. Inflammation, microbiome signatures, and external selective pressures also contribute to clonal evolution. Despite significant progress in recent years, the precise molecular mechanisms driving CH transformation to hematologic neoplasms are not well defined. Further understanding of these complex mechanisms may improve risk stratification and introduce therapeutic interventions in CH. Here we discuss the genetic drivers underpinning CH, mechanisms for clonal evolution, and transformation to hematologic neoplasm.

Abstract Introduction The occurrence of other neoplasms in patients diagnosed with chronic lymphocytic leukemia (CLL) is a known but insufficiently studied complication, highlighting the need for further research. Our study aims to analyze the incidence of other malignancies in CLL. Methods We performed a retrospective observational study of patients diagnosed with CLL between 2000-2016 at our center. Variables collected included: demographics, stage at diagnosis, treatment, response to treatment, death, other neoplasm (type, date of diagnosis, outcome), biomarker profiles studied by karyotyping, FISH, immunoglobulin heavy chain gene variable region mutational status, and TP53 mutational status. A descriptive study was performed. Quantitative variables are described as medians with their range, and qualitative variables as percentages. The relationship between qualitative variables and the development of second malignancies was performed using Chi-square and Fisher's exact test. Survival analyses were performed using the Kaplan-Meier method and the difference between groups was analyzed using the log-rank test. Results A total of 182 patients were evaluated, 104 men (57%) and 78 women (43%); median age: 74 years (39 - 97). Most patients were diagnosed at early stages (74% at Rai stage 0 and 84% at Binet stage A) and the median CIRS scale score at diagnosis was 4 (0 - 15). With a median follow-up of 76 months (20-212), 77/182 (42%) patients had received ≥1 line(s) of treatment: 1: 53%, 2: 26%, 3: 8%, ≥4: 13%. Forty-nine cases (27%) were reported with other malignancies in addition to CLL; cases with Richter transformation (n=5, 2.7%) were excluded. The diagnosis of CLL preceded the other neoplasm in 33/182 cases (18%): 8 hematologic and 27 non-hematologic neoplasms. Half of the hematologic malignancies involved MGUS (n=4), 1 mutated JAK2 (V617F) cMPN, 1 AML and 1 MALT lymphoma. As for non-hematologic tumors, non-melanoma skin cancer accounted for 30% of cases (n=8), followed by breast cancer (n=5, 18.5%). Neoplasms of the stomach, colon, liver, bladder and prostate together accounted for 37%, in the same proportion each (n=2, 7.4%). The remaining neoplasms corresponded to lung and bronchus, kidney, melanoma and pancreas. Five of the 27 patients had a third solid organ neoplasm, with non-melanoma skin cancer again being the most frequent (n=2). The other neoplasms were lung, small bowel and thyroid. The incidence of second neoplasms was higher in treated patients (26% vs. 12.4%, p=0.019). The incidence of a second hematologic malignancy was related to treatment administration (9%) compared to 1% in untreated patients (p=0.011), especially in those with ≥ 3 lines (37.5% vs. 3%), p=0.024. We could not find any association between the variables analyzed and the development of second non-hematologic malignancies. The development of second neoplasms after the diagnosis of CLL did not have a negative impact on the overall survival of these patients. Conclusions The incidence of second malignancies is high in patients with CLL, being higher in those patients who have received treatment, and especially in those with a greater number of lines received. In contrast, the development of solid tumors did not seem to be affected by treatment administration, which should motivate further investigation in specific subgroups of patients. In our series, the development of second neoplasms after the diagnosis of CLL did not have a negative impact on the overall survival of these patients. Disclosures Gonzalez-Lopez: Novartis: Other: Advisoryboard and speakers honoraria, Research Funding; Amgen: Other: Advisory board and speakers honoraria, Research Funding; Sobi: Other: Advisory board honoraria; Grifols: Other: Advisory board honoraria.

Abstract Abstract 3636 Hodgkin lymphoma, especially the young adult type, is one of the most heritable cancers. We previously reported a high risk of Hodgkin lymphoma to monozygotic (MZ), but not dizygotic (DZ) co-twins of cases, and only a modest difference in risk between MZ and DZ co-twins of non-Hodgkin lymphoma (NHL) cases (Mack, 1995). After an additional 18 years of follow-up, we have now updated the observed occurrence of hematologic malignancies in the initially unaffected co-twins of HL, NHL, multiple myeloma (MM), and chronic lymphocytic leukemia (CLL) twin probands. The number of calendar and age-specific person-years at risk for each co-twin was calculated from the date of diagnosis of the proband to the date of last follow-up of the co-twin, defined by the last date of contact, date of death ascertained directly or from linkage with the National Death Index, or evidence of current vital status from a national tracing program. The expected number of cases was calculated by applying the calendar and age-specific incidence rates by 5-year interval categories for each hematologic neoplasm from the Surveillance, Epidemiology and End-Results Program to the person-years of risk. Diagnoses of hematological neoplasms in the co-twins by age and year were ascertained by direct follow-up augmented by a linkage with the National Death Index, using diagnoses categorized by the ICD-9 codes. The standardized incidence ratio (SIR) was computed as the observed to expected number of cases; 95% confidence intervals (CI) (Breslow and Day, 1987), and the risk ratio (RR) (ratio of the SIR in MZ co-twins compared to that in DZ co-twins) were calculated. Whereas the SIR for DZ co-twins measures the heritable and acquired components of risk to first-degree family members, the RR provides evidence of genetic heritability, based on the additional genomic commonality of MZ twins. A total of 364 (HL), 501 (NHL), 91 (MM), and 45 (CLL) co-twins of probands contributed to the analysis. The risk of developing the same hematologic neoplasm as the proband was generally higher in the MZ compared to the DZ co-twins, with the highest RR observed for HL (13.3) and the lowest for NHL (1.75). Although more than 10,000 person-years were added since the original paper, the RR's for HL and NHL did not change substantially from those reported in 1995. The RR for CLL was 3.3 suggesting moderately strong heritability. One MZ co-twin developed MM producing a large SIR, however chance cannot be easily ruled out. The findings of most interest are the continued very high risk of HL in MZ compared to DZ twins confirming the strong heritability of this neoplasm, and the relatively low RR for NHL. MZ and DZ co-twins of NHL probands had increased but similar SIR's, suggesting that shared environmental factors are more important than heritability. Subtype–specific information on the NHL type was not available from the ICD-9 codes used by the Death Index to identify new cases, so it is possible that stronger NHL heritability would be evident if subtypes were considered separately. Table 1. Occurrence of similar hematologic neoplasms in co-twins of lymphoma and chronic lymphocytic leukemia probands Neoplasm Type Zygosity No. at risk No. Cases Expected No. Cases Observed SIR1 (95% CI2) Risk Ratio: SIR1MZ/SIR1DZ Hodgkin lymphoma MZ 170 0.11 13 114.2 (60.7, 195.3) 13.3 DZ 194 0.12 1 8.6 (0.1, 47.6) Non-Hodgkin lymphoma MZ 213 0.51 6 11.8 (4.3, 25.7) 1.75 DZ 288 0.74 5 6.7 (2.2, 15.7) Multiple myeloma MZ 51 0.03 1 28.8 (0.38, 160,3) NA DZ 40 0.02 0 0 Chronic lymphocytic leukemia MZ 25 0.01 4 260.9 (70.2, 668,0) 3.3 DZ 20 0.01 1 79.8 (1.0, 444.0) 1 Standardized incidence ratio 2 95% Confidence intervals Disclosures: No relevant conflicts of interest to declare.

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Mestrado Acadêmico em Ciências do Cuidado em Saúde
Trata-se de uma pesquisa qualitativa, descritiva do tipo estudo de caso único, que teve como objeto de estudo cuidados de enfermagem aos pacientes onco-hematológicos hospitalizados e os seguintes objetivos: caracterizar o perfil dos pacientes onco-hematológicos hospitalizados na enfermaria de hematologia do Hospital Universitário Antônio Pedro (HUAP), identificar as demandas de cuidado dos pacientes onco-hematológicos hospitalizados na enfermaria de hematologia do HUAP, descrever os cuidados realizados pela equipe de enfermagem aos pacientes onco-hematológicos hospitalizados na enfermaria de hematologia do HUAP, elaborar um protocolo de cuidados de enfermagem aos pacientes onco-hematológicos hospitalizados na enfermaria de hematologia do HUAP, a partir dos relatos dos membros da equipe de enfermagem. O cenário de pesquisa foi à unidade de hematologia do HUAP. Fizeram parte do estudo 17 sujeitos, sendo sete (7) pacientes hospitalizados com diagnóstico médico de LMA, LMC, LLA, LLC, Linfoma de Hodgkin e Não-Hodgkin e dez (10) membros da equipe de enfermagem. A coleta de dados foi através do formulário de identificação e o histórico de enfermagem com os pacientes e a observação participante acerca do cuidado de enfermagem ao paciente onco-hematológico hospitalizado e as entrevistas com a equipe de enfermagem. Os resultados apontaram como demandas de cuidado de enfermagem àqueles relacionados à atenção, cuidados gerais, ambiente de cuidado; orientação à família e ao paciente e equipe especializada. Com relação ao cuidado que a equipe de enfermagem realiza foram identificados: cuidado prevenção; cuidado sensível; cuidado clínico; cuidado atributos; cuidado educativo. E o cuidado específico ao paciente onco-hematológico está atrelado à prevenção, conforto, apoio emocional e orientação e tais cuidados foram os subsídios para a elaboração do protocolo de cuidado de enfermagem a estes pacientes segundo a realidade local do HUAP. Desta forma, tal protocolo consolida o que a enfermagem do serviço de hematologia do HUAP já vem realizando. Além disso, torna-se aos membros desta equipe um apoio na prestação da assistência de enfermagem de modo que possam identificar no protocolo os cuidados específicos direcionados as demandas de cuidados destes pacientes.
This is a qualitative, descriptive research of type single case study, which had as its object of study nursing care to onco-hematological patients hospitalized and the following goals: characterize the profile of onco-hematological patients hospitalized in hematology ward of the University Hospital Antônio Pedro (HUAP), identifying the demands of care of oncohematological patients hospitalized in hematology ward of HUAP, describing the care provided by nursing staff to onco-hematological patients hospitalized in hematology ward of HUAP, draw up a protocol of nursing care to onco-hematological patients hospitalized in hematology ward of HUAP, from reports of the members of the nursing staff. The scenario of research was the Hematology unit of HUAP. Were part of the study 17 subjects, being seven (7) hospitalized patients with medical diagnosis of LMA, LMC, LLA, LLC, Hodgkin's lymphoma and non-Hodgkin lymphoma and ten (10) members of the nursing staff. The data collection was through the identification form and the nursing history with patients and the participant observation about nursing care to the onco-hematological patient hospital and interviews with the nursing staff. The results showed how nursing care as demands related to attention, general care, environment of care; guidance to the family and the patient and expert staff. With respect to the care that nursing staff conducts were identified: preventive care; sensitive care; clinical care; careful attributes; educational care. And patient specific oncohematological care is related to prevention, comfort, emotional support and guidance and such care was the allowances for nursing care protocol to these patients according to the local reality of HUAP. In this way, such a protocol that consolidates what the Hematology nursing service of HUAP already has been performing. Moreover, it becomes to members of this team a support in the provision of nursing care so that they can identify the protocol specific targeted care demands these patients.

As anormalidades hematológicas de origem paraneoplásica são identificadas em diversos tipos de neoplasias que acometem cães e gatos. Nas neoplasias mamárias em cadelas, já foram identificadas anormalidades relacionadas com a coagulação, onde verificou-se que a coagulação intravascular disseminada (CID) clínica e subclínica pode estar presente em 83% das cadelas com carcinoma mamário. Na medicina humana, é dada relevância à investigação de tais alterações uma vez que são fatores indicadores de prognóstico do câncer. Enquanto isso, na medicina veterinária, são escassos os estudos que relacionam as alterações hematológicas com o tipo tumoral, estadiamento e determinação de prognóstico. O objetivo do presente estudo foi realizar a avaliação hematológica, bioquímica e da hemostasia de cadelas acometidas por neoplasia mamária para identificar a alteração mais frequente, além de relacionar as anormalidades com o estadiamento tumoral. Para isso, foram utilizadas 25 cadelas atendidas pelo Grupo de Estudos em Oncologia em pequenos animais (ONCOVET) do Hospital de Clínicas Veterinárias da UFRGS (HCV-UFRGS) durante o período de 4 meses. Foi realizado coleta de sangue para hemograma, contagem de plaquetas, bioquímica sérica (albumina, ALT, cálcio, creatinina, FA, glicose, ureia) e teste de coagulação que constou de TP (tempo de protrombina), TTPa (tempo de tromboplastina parcial ativada), TT (tempo de trombina), fibrinogênio e mensuração do dímero-D. O estadiamento tumoral foi obtido através do exame físico e do resultado da biopsia das mamas. As anormalidades encontradas incluíram anemia, leucocitose neutrofílica, monocitose, eosinofilia, trombocitose, hipoalbuminemia, hipocalcemia, hipoglicemia e diminuição dos níveis de ureia sanguínea. Entretanto, essas alterações não foram relacionadas diretamente com a progressão tumoral, uma vez que não houve diferença entre os grupos avaliados. Apenas as variáveis RDW e ALT apresentaram relação significativa entre os grupos, contudo, sem relevância clínica. No teste de coagulação, houve diferença significativa entre os grupos apenas no TT e fibrinogênio, que foi relacionado com o estadiamento tumoral.
Hematological abnormalities of paraneoplastic origin are identified in several types of cancers that affect dogs and cats. In dogs with mammary neoplasms, abnormalities associated with coagulation have been identified, and verified that disseminated intravascular coagulation (DIC) clinical and subclinical may be present in 83% of dogs with mammary carcinoma. In human medicine, research in this field has been relevant since those factors are indicators of cancer prognosis. Meanwhile, in veterinary medicine, there are few studies that relate hematological changes with tumor type, staging and determination of prognosis. The aim of this study was to evaluate the hematological, biochemical and hemostathic abnormalities in bitches affected by mammary cancer to identify the most frequent alteration and associate with tumor staging. For this, 25 bitches attended by the Oncology Study Group in small animals (ONCOVET) of the Veterinary Hospital of UFRGS (HCV-UFRGS) for the period of 4 months were used. Blood collection for complete blood count, platelet count, serum biochemistry (albumin, ALT, calcium, creatinine, ALP, glucose, urea) and coagulation test that consisted of PT (prothrombin time), aPTT (activated partial thromboplastin time), TT (thrombin time), fibrinogen and D-dimer measurement were performed. Tumor staging was obtained by physical examination and the results of the biopsy of the breast. The abnormalities found included anemia, neutrophilic leukocytosis, monocytosis, eosinophilia, thrombocytosis, hypoalbuminemia, hypocalcemia, hypoglycemia and decreased levels of urea. However, these changes were not associated directly with tumor progression, since there was no difference among the groups. Only the RDW and ALT variables was associated significantly between the groups, however, with no clinical relevance. In the coagulation test, there was significant difference between the groups only in TT and fibrinogen, which was associated with tumor staging.

Abstract The investigation of the web of relationships between the different elements of the immune system has proven instrumental to better understand this complex biological system. This is particularly true in the case of the interactions between B and T lymphocytes, both during cellular development and at the stage of cellular effectors functions. The understanding of the B–T cells interdependency and the possibility to manipulate this relationship may be directly applicable to situations where immunity is deficient, as is the case of cancer or immune suppression after radio and chemotherapy. The work presented here started with the development of a novel and accurate tool to directly assess the diversity of the cellular repertoire (Chapter III). Contractions of T cell receptor diversity have been related with a deficient immune status. This method uses gene chips platforms where nucleic acids coding for lymphocyte receptors are hybridized and is based on the fact that the frequency of hybridization of nucleic acids to the oligonucleotides on a gene chip varies in direct proportion to diversity. Subsequently, and using this new method and other techniques of cell quantification I examined, in an animal model, the role that polyclonal B cells and immunoglobulin exert upon T cell development in the thymus, specifically on the acquisition of a broader repertoire diversity by the T cell receptors (Chapter IV and V). The hypothesis tested was if the presence of more diverse peptides in the thymus, namely polyclonal immunoglobulin, would induce the generation of more diverse T cells precursors. The results obtained demonstrated that the diversity of the T cell compartment is increased by the presence of polyclonal immunoglobulin. Polyclonal immunoglobulin, and particularly the Fab fragments of the molecule, represent the most diverse self-molecules in the body and its peptides are presented by antigen presenting cells to precursor T cells in the thymus during its development. This probably contributes significantly to the generation of receptor diversity. Furthermore, we also demonstrated that a more diverse repertoire of T lymphocytes is associated with a more effective and robust T cell immune function in vivo, as mice with a more diverse T cell receptors reject minor histocompatiblility discordant skin grafts faster than mice with a shrunken T cell receptor repertoire (Chapter V). We believe that a broader T cell receptor diversity allows a more efficient recognition and rejection of a higher range of external and internal aggressions. In this work it is demonstrated that a reduction of TCR diversity by thymectomy in wild type mice significantly increased survival of H-Y incompatible skin grafts, indicating decrease on T cell function. In addiction reconstitution of T-cell diversity in mice with a decreased T cell repertoire diversity with immunoglobulin Fab fragments, lead to a increase on TCR diversity and to a significantly decreased survival of the skin grafts (Chapter V). These results strongly suggest that increases on T cell repertoire diversity contribute to improvement of T cell function. Our results may have important implications on therapy and immune reconstitution in the context of AIDS, cancer, autoimmunity and post myeloablative treatments. Based on the previous results, we tested the clinical hypothesis that patients with haematological malignancies subjected to stem cell transplantation who recovered a robust immune system would have a better survival compared to patients who did not recover such a robust immune system. This study was undertaken by the examination of the progression and overall survival of 42 patients with mantle cell non-Hodgkin lymphoma receiving autologous hematopoietic stem cell transplantation (Chapter VI). The results obtained show that patients who recovered higher numbers of lymphocytes soon after autologous transplantation had a statistically significantly longer progression free and overall survivals. These results demonstrate the positive impact that a more robust immune system reconstitution after stem cell transplantation may have upon the survival of patients with haematological malignancies. In a similar clinical research framework, this dissertation also includes the study of the impact of recovering normal serum levels of polyclonal immunoglobulin on the survival of patients with another B cell haematological malignancy, multiple myeloma, after autologous stem cell transplantation (Chapter VII). The relapse free survival of the 110 patients with multiple myeloma analysed was associated with their ability to recover normal serum levels of the polyclonal compartment of immunoglobulin. These results suggest again the important effect of polyclonal immunoglobulin for the (re)generation of the immune competence. We also studied the impact of a robust immunity for the response to treatment with the antibody anti CD20, rituximab, in patients with non- Hodgkin’s lymphoma (NHL) (Chapter VIII). Patients with higher absolute counts of CD4+ T lymphocytes respond better (in terms of longer progression free survival) to rituximab compared to patients with lower number of CD4+ T lymphocytes. These observations highlight again the fact that a competent immune system is required for the clinical benefit of rituximab therapy in NHL patients. In conclusion, the work presented in this dissertation demonstrates, for the first time, that diverse B cells and polyclonal immunoglobulin promote T cell diversification in the thymus and improve T lymphocyte function. Also, it shows that in the setting of immune reconstitution, as after autologous stem cell transplantation for mantle cell lymphoma and in the setting of immune therapy for NHL, the absolute lymphocyte counts are an independent factor predicting progression free and overall survival. These results can have an important application in the clinical practice since the majority of the current treatments for cancer are immunosuppressive and implicate a subsequent immune recovery. Also, the effects of a number of antineoplastic treatments, including biological agents, depend on the immune system activity. In this way, studies similar to the ones presented here, where methods to improve the immune reconstitution are examined, may prove to be instrumental for a better understanding of the immune system and to guide more efficient treatment options and the design of future clinical trials. Resumo O estudo da rede de inter-relações entre os diversos elementos do sistema immune tem-se mostrado um instrumento essencial para uma melhor compreensão deste complexo sistema biológico. Tal é particularmente verdade no caso das interacções entre os linfócitos B e T, quer durante o desenvolvimento celular, quer ao nível das funções celulares efectoras. A compreensão da interdependência entre linfócitos B e T e a possibilidade de manipular esta relação pode ser directamente aplicável a situações em que a imunidade está deficiente, como é o caso das doenças neoplásicas ou da imunossupressão após radio ou quimioterapia. O trabalho apresentado nesta dissertação iniciou-se com o desenvolvimento de um novo método laboratorial para medir directamente a diversidade do reportório celular (Capítulo III). Reduções da diversidade do reportório dos receptores de células T têm sido relacionadas com um estado de imunodeficiência. O método desenvolvido utiliza “gene chips”, aos quais hibridizam os ácidos nucleicos codificantes das cadeias proteicas dos receptores linfocitários. A diversidade é calculada com base na frequência de hibridização do ácido nucleico da amostra aos oligonucleótidos presentes no “gene chip”. De seguida, e utilizando este novo método e outras técnicas de quantificação celular examinei, num modelo animal, o papel que as células policlonais B e a imunoglobulina exercem sobre o desenvolvimento linfocitário T no timo, especificamente na aquisição de um reportório diverso de receptores T (Capítulos IV e V). Testei, então, a hipótese de que a presença no timo de péptidos mais diversos, como a imunoglobulna policlonal, induzisse a génese de precursores T mais diversos. Demonstrámos que a diversidade do compartimento T é aumentado pela presença de imunoglobulina policlonal. A imunoglobulina policlonal, e particularmente os fragmentos Fab desta molécula, representam as moléculas autólogas mais diversas presentes nos organismos vertebrados. Estes péptidos são apresentados por células apresentadoras de antigénio às células precursoras T no timo, durante o desenvolvimento celular T. Tal, provavelmente, contribui para a génese da diversidade dos receptores. Também demonstrámos que a presença de um reportório mais diverso de linfócitos T se associa a um incremento da função imunológica T in vivo. Uma diversidade de receptores T mais extensa parece permitir um reconhecimento e rejeição mais eficientes de um maior número de agressores internos e externos. Demonstrámos que ratinhos com receptores de células T (RCT) com maior diversidade rejeitam transplantes cutâneos discordantes para antigénios minor de histocompatibilidade mais rapidamente do que ratinhos com um menor reportório T (Capítulo V). Por outro lado, uma redução da diversidade do RCT, causada por timectomia de ratinhos de estirpes selvagens, mostrou aumentar significativamente a sobrevivência de transplantes cutâneos incompatíveis para o antigénio H-Y (antigénio minor de histocompatibilidade), indicando uma diminuição da função linfocitária T. Além disso, a reconstituição da diversidade dos linfócitos T em ratinhos com uma diversidade de reportório T diminuída, induzida pela administração de fragmentos Fab de imunoglobulina, conduz a um aumento da diversidade dos RCT e a uma diminuição significativa da sobrevivência dos enxertos cutâneos (Capítulo V). Estes resultados sugerem que o aumento do reportório de células T contribui para uma melhoria das funções celulares T e poderão ter implicações importantes na terapêutica e reconstitutição imunológica em contexto de SIDA, neoplasias, autoimunidade e após tratamentos mieloablativos. Baseado nos resultados anteriores, decidimos testar a hipótese clínica de que doentes com neoplasias hematológicas sujeitos a transplantação de precursores hematopoiéticos e com recuperação imunológica precoce após transplante teriam uma sobrevivência mais longa do que doentes que não recuperassem tão bem a sua imunidade. Analisámos a sobrevivência global e sobrevivência sem doença de 42 doentes com linfoma não Hodgkin de células do manto sujeitos a transplante autólogo de precursores hematopoiéticos (Capítulo VI). Os resultados obtidos mostraram que os doentes que recuperaram contagens mais elevadas de linfócitos imediatamente após o transplante autólogo, apresentaram uma sobrevivência global e sem progressão mais longa do que doentes que não recuperaram contagens linfocitárias tão precocemente. Estes resultados demonstram o efeito positivo de uma reconstitutição imunológica robusta após transplante de presursores hematopoiéticos, sobre a sobrevivência de doentes com neoplasias hematológicas. Do mesmo modo, estudámos o efeito que a recuperação de níveis séricos normais de imunoglobulina policlonal tem na sobrevivência de doentes com outras neoplasias hematológicas de linfócitos B, como o mieloma múltiplo,após transplante autólogo de precursos hematopoiéticos (Capítulo VII). A sobrevivência livre de doença dos 110 doentes com mieloma múltiplo analizados está associada com a sua capacidade de recuperar níveis séricos normais do compartmento policlonal de imunoglobulina. Estes resultados pioneiros indicam a importância da imunoglobulina policlonal para a génese de competência imunológica. Também estudámos o impacto de um sistema imunitário eficiente sobre a resposta ao tratamento com o anticorpo anti CD20, ituximab, em doentes com linfoma não Hodgkin (LNH) (Capítulo VIII). Os resultados mostram que doentes com valores mais elevados de linfócitos T CD4+ respondem melhor (em termos de maior sobrevida livre de doença) ao rituximab, do que doentes com valores mais baixos. Estas observações ilustram a necessidade de um sistema imunitário competente para o benefício clínico da terapêutica com rituximab em doentes com LNH. Em conclusão, o trabalho apresentado nesta dissertação demonstra que as células B e a imunoglobulina policlonal promovem a diversidade das células T no timo e melhoram a função linfocitária T periférica. Concomitantemente, também demonstrámos que, no contexto de reconstituição imune, por exemplo, após transplante autólogo de precursores hematopoiéticos em doentes com linfomas de células do manto, o número absoluto de linfócitos é uma factor independente da sobrevivência. Os resultados demonstram, também, a importância dos valores de linfocitos T na resposta ao tratamento com rituximab no caso de doentes com LNH. O mesmo princípio se prova pelo facto de que doentes com mieloma múltiplo sujeitos a transplante autólogo de precursores hematopoiéticos que recuperam valores normais séricos de imunoglobulinas policlonais, terem melhores taxas de resposta em comparação com doentes que não recuperam valores normais de imunoglobulinas policlonais. Estes resultados podem ter importantes aplicações na prática clínica dado que a maioria dos tratamentos de doenças neoplásicas implica imunossupressão e, subsequente, recuperação imunológica. Estes estudos podem ser um instrumento fundamental para uma melhor compreensão do sistema imune e guiar uma escolha mais eficiente de opções terapêuticas bem como contribuir para a concepção de futuros estudos clínicos.

The latest version of the World Health Organization guidelines focuses mainly on the genetic and cytogenetic features of hematologic neoplasms as predictors of diagnostic, treatment decision, prognostic outcome, and for treatment monitoring in hematological malignancies. There are different techniques to identify these abnormalities. Live cells are needed for chromosome preparation. The Hematological malignancies include myeloid and lymphoid neoplasms. The myeloid neoplasms include Myelodysplastic syndromes, myeloproliferative neoplasms, and acute myeloid leukemias. The Lymphoid neoplasms include acute and chronic lymphocytic leukemias, plasma cell neoplasms, myeloma, hodgkin, and non-hodgkin lymphomas. The first chromosomal abnormality discovered in connection with cancer is the Philadelphia chromosome, which is an abnormal chromosome 22, formed due to the translocation between chromosomes 9 and 22. The presence of this abnormal chromosome confirms the diagnosis of “CML”. After that, hundreds of chromosomal abnormalities have been identified in hematological malignancies in different parts of the world. In AML, specific abnormalities were identified as having a good prognosis, intermediate prognosis, and poor prognosis. In other hematological malignancies also there some specific chromosome abnormalities are associated with prognostication. Now a day’s clinicians depend mainly on genetic abnormalities for the proper treatment management of hematological malignancies, so the study of chromosomal abnormalities is essential.

Introdução: Leucemia linfoide aguda é um tipo de neoplasia que atinge as células do sangue. A doença surge, primordialmente, na medula óssea, que se dá pela proliferação desregulada na produção de células imaturas. Acomete, sobretudo, crianças de 2 a 5 anos de idade, mas totalmente fatal quando diagnosticada em fase tardia. Os exacerbados índices dessa neoplasia em crianças, causam consequências graves, tanto para a vida pessoal, como no seu desenvolvimento social. Objetivo: Descrever os efeitos da leucemia linfoide aguda na qualidade de vida dos pacientes pediátricos. Material e métodos: Trata-se de uma revisão narrativa da literatura, na qual foram utilizadas as bases de dados do Scielo. Foram selecionados artigos da língua portuguesa e estudos publicados entre os anos de 2019 e 2022. Utilizou- se os descritores: Leucemia, Neoplasia Hematológica e Pediatria. Os critérios de inclusão foram estudos originais, como critérios de exclusão; artigos que não correlacionaram com o objetivo do estudo, totalizando 14 artigos selecionados. Resultados: Após análise minuciosa de literatura, destaca-se que na população infantil a leucemia é o tipo mais comum de neoplasia, com cerca de 75% dos casos sendo de leucemia linfoide aguda. Nesse contexto, ao relacionar com a vivência do público infantil, pode-se afirmar que esta neoplasia hematológica influencia na qualidade do desenvolvimento pessoal e social, pois há necessidade da criança se ausentar do ambiente escolar para cuidados com a saúde. Em resultância do afastamento do lugar primordial para trocas de experiências por conta da doença, tem-se um sujeito com interação social comprometida. Com isso, cresce um indivíduo com comportamento retraído e com dificuldade de expressar sua opinião na sociedade, de modo que doenças psicológicas oportunistas podem surgir, como depressão e ansiedade. Conclusão: É evidente que a leucemia linfoide aguda interfere na qualidade de vida de crianças em âmbito íntimo e social, de forma que favorece o surgimento de mazelas da mente.

Introdução: Atualmente cada vez mais pessoas são diagnosticadas com doenças oncológicas. Dentre o conjunto demais de 100 doenças que envolvem o câncer, as neoplasias hematológicas, por se tratar de doenças com alteração no sangue e em tecidos apresenta uma incidência de 257 mil novos casos ano. O tratamento atualmente é a quimioterapia, com resultados de cura para muitos e aumento de sobrevida, no entanto os efeitos invasivos da terapia oncológica deixam o organismo vulnerável e debilitado, prejudicando a qualidade de vida dos pacientes. Objetivo: Descrever como é a qualidade de vida dos pacientes com neoplasia hematológica, que realizam quimioterapia, e indicar maneiras de melhorar fatores que interfiram na qualidade de vida do paciente. Metodologia: Realizou-se uma pesquisa bibliográfica utilizando artigos originais nas bases de dados Biblioteca Virtual em Saúde e Scielo. Os descritores foram Qualidade de Vida, Quimioterapia e Neoplasia Hematológica. Os critérios de inclusão foram artigos nos idiomas inglês e português, publicados nos últimos cinco anos. Posteriormente, descartou-se estudos duplicados, não gratuitos e que não atendiam ao objetivo proposto. Resultados: Dentre os estudos a média analisada foram de duas a 24 semanas com as sessões de quimioterapia variando de uma a 80 sessões. Sendo que os efeitos colaterais são náuseas, alopecia, mucosite e inapetência. Dentre as analises os pacientes relatam que a sua qualidade de vida é boa, quando questionados sobre a saúde mostraram-se satisfeitos. No entanto, apresentaram um isolamento social, nesse sentido o convívio com os familiares e amigos que estimulam a pratica de atividades são importantes fatores positivos. Outro fator bastante relatado é a falta de remuneração durante o tratamento, muitos pacientes não tem condições de manter seus empregos durante os tratamentos. Dentre os domínios físicos, as limitações e os efeitos colaterais são refletidos na diminuição da função física e qualidade de vida. Conclusões: Ao se tratar de uma doença que provoca debilidade e dificuldades, a convivência familiar, pratica de exercícios ter uma vida social podem contribuir de forma significativa na qualidade de vida do paciente

Introdução: A infecção pelo SARS-CoV-2, têm se mostrado mundialmente perigosa, especialmente para grupos mais vulneráveis. Nesse cenário, pacientes de COVID-19 que apresentam neoplasias hematológicas se mostram mais propícios a um desfecho de quadro mais agressivo ou fatal. Objetivos: Verificar se um histórico de Neoplasia Hematológica (NH) está associado a uma maior taxa de gravidade e de mortalidade em pacientes da COVID-19. Material e métodos: Neste estudo analítico descritivo, foram coletados dados de artigos originais referentes a pesquisas relacionadas à COVID-19, contendo informações a respeito do desenvolvimento do quadro da doença em pacientes acometidos por neoplasias hematológicas. Para critério de inclusão, utilizou-se trabalhos publicados nos anos de 2020 e 2021 nas plataformas Scielo e PubMed, e os termos HEMATOLOGIA, NEOPLASIA HEMATOLÓGICA e COVID-19 foram usados para as buscas. Resultados: Dentre os diversos métodos de pesquisa analisados, há a convergência acerca da maior taxa de ocorrência de mortalidade, e de casos graves, da doença em pacientes que também possuíam neoplasias hematológicas do que na população geral afetada por esse mal; assim como quando comparados com pacientes de neoplasias hematológicas não infectados pelo vírus. A presença do câncer hematológico quando comparada a de tumores sólidos, se mostrou mais fatal, com taxa de mortalidade de 41% e 17%, respectivamente, em estudos com amostragem pequena o que torna a comparação ainda controversa. A maior susceptibilidade de infecção por COVID-19 dos pacientes de Neoplasias Hematológicas não é abordada com profundidade nos resultados, embora seja referida uma menor contagem de plaquetas e hemoglobinas nos pacientes quando infectados, e o prognóstico desses pacientes ainda passa por estudos. É destacado também, que pacientes não tratados contra a malignidade, possuíam mais chance de sobrevivência à infecção pelo SARS-CoV-2 quando comparados aos pacientes que estavam em tratamento, ou passaram por algum tipo de tratamento recente. Conclusão: O risco acentuado de desfecho desfavorável para um paciente com Neoplasia Hematológica frente a COVID-19, mostra a necessidade da manutenção de estratégias preventivas de infecções até a efetivação de um tratamento, mesmo no atual cenário vacinal.

Introdução: A leucemia linfoide aguda (LLA) é uma neoplasia hematológica que acomete a diferenciação celular e a proliferação exacerbada de células precursoras das linhagens B, T e Natural Killer, apresentando maior incidência na faixa pediátrica. O receptor para o fator de crescimento transformador beta (TGFβR) parece estar envolvido em doenças hematológicas, e um polimorfismo de nucleotídeo único foi identificado em sua região promotora (G-875A) parecendo modificar a expressão de TGFβRII nas células. Objetivo: Avaliar o envolvimento do TGFβRII G-875A na LLA infantil brasileira, com foco na suscetibilidade, parâmetros clínico-patológicos e estratificação de risco. Material e métodos: Estudo de associação caso-controle, envolvendo 127 pacientes com LLA e 161 crianças livres de neoplasia. A avaliação foi realizada através da reação em cadeia da polimerase (PCR) seguida da análise do polimorfismo do comprimento do fragmento de restrição (RFLP). Resultados: Em relação à distribuição dos genótipos, não houve diferença estatisticamente significativa entre os subgrupos de LLA e as crianças controle. Verificou-se que o G-875A foi estatisticamente associado ao aumento da suscetibilidade para LLA-B no modelo recessivo (OR = 2,16; IC = 1,02–4,57; p <0,05), também foi observada associação significativamente aumentada para alto risco (AR) para recidiva no mesmo modelo (OR = 5,14; IC = 1,05–25,12; p <0,05). Além disso, foi observada correlação positiva entre o grupo de risco e o polimorfismo G-875A no modelo recessivo na LLA-B (p = 0,02). Em relação à LLA-T, foi observada correlação positiva entre recidiva e G-875A nos modelos aditivo e dominante (p=0,05 e p=0,028, respectivamente). Conclusão: Verificou-se que o G-875A foi associado ao aumento da suscetibilidade para LLA-B e AR para recidiva em modelo recessivo. Também houve correlação positiva entre a recidiva de LLA e G-875A nos modelos aditivo e dominante, podendo este polimorfismo ser um forte candidato a um possível marcador prognóstico na LLA.

Introdução: Linfoma ou doença de Hodgkin, descrito em 1832 por Thomas Hodgkin, é uma neoplasia linfoide caracterizada pela proliferação de células de morfologia anormal, denominadas Células de Reed-Sternberg (CRS) que aparecem quando ocorre a malignização de linfócitos B. A classificação da Organização Mundial da Saúde (OMS), comumente empregada, divide o linfoma de Hodgkin (LH) em duas categorias: LH clássico e LH de predomínio linfocitário nodular. A forma clássica da doença corresponde a cerca de 90% dos casos e apresenta quatro subtipos: rico em linfócitos, celularidade mista, depleção linfocitária e esclerose nodular, sendo esta última a mais recorrente. A manifestação mais comum do LH é a linfadenopatia indolor em região cervical com gânglios de consistência fibroelástica, pode também estar presente nas regiões torácica, axilar, abdominal ou inguinal. Além disso, outros sintomas acompanham o quadro clínico como febre, sudorese noturna, emagrecimento e fraqueza. Já os pacientes com ausência linfadenomegalia periférica mostram uma massa mediastinal em radiografia de tórax. Com a evolução do linfoma podem surgir manifestações como tosse seca, dor torácica e dispneia com piora na posição supina, o que indica comprometimento dos hilos pulmonares e parede torácica. Ainda pode ocorrer, mesmo que raramente, um prurido intenso e disseminado. Objetivo: Descrever as características do linfoma de Hodgkin, e pontuar as manifestações clínicas mais comuns envolvidas no processo de adoecimento/evolução dessa doença. Material e Métodos: O presente trabalho trata-se de uma revisão integrativa da literatura. O levantamento bibliográfico foi realizado através de artigos, coletados nas bases de dados da SciELO, BVS e LILIACS com recorte temporal de 5 anos utilizando o descritor português “doença de Hodgkin” e sua variação na língua inglesa, o qual foi confirmado no DeCS/MeSH, bem como livros específicos na área da hematologia. Resultados: Dentre os documentos analisados destacou-se como apresentação mais comum do LH, a tumoração cervical indolor com aspecto fibroelástico (de borracha). A sintomatologia auxilia no diagnóstico juntamente com a realização de biópsia. Conclusão: Mediante as informações coletadas conclui-se que a Doença de Hodgkin, refere-se a uma neoplasia com bom prognóstico e curável quando tratada de forma adequada.

Introduction: Ovarian fibrothecomas represent an ovarian stromal neoplasm developing in a wide spectrum of clinical settings. These tumors have been described as rare ovarian neoplasm, accounting for about 4% of all ovarian tumors. We report a case whose clinical presentation was highly deceptive and was clinically and radiologically diagnosed as malignant ovarian tumor. Ascitic fluid cytology revealed absence of malignant cells. On histopathological examination, it was diagnosed as benign fibrothecoma with cystic changes. Postoperative follow-up for about six months was uneventful. Case: A 45 year old female presented to the gynae emergency with large abdominal lump of 20 weeks size with acute pain abdomen. She was admitted for initial management and thorough evaluation. Hematological and biochemical parameters were within normal limits. USG revealed a large multilocular, predominantly cystic lesion 20.9x9.6x11.4 cm in pelvis. CECT revealed ovarian cystadencarcinoma left ovary with locoregional mass effect, mild ascites and suspicious metastasis to internal iliac lymph nodes. Radiological and preoperative clinical diagnosis was malignant ovarian tumor. Panhysterectomy and omentectomy was performed. On gross examination, a well encapsulated, multinodular cystic tumor of left ovary about 17x14x7 cm was identified. Cut surface was mostly solid with few cystic areas. Uterus, cervix, right ovary and both tubes were unremarkable. On microscopic examination, multiple sections showed spindle shaped cells in storiform and palisading pattern. No mitotic activity was identified. On special staining, it was positive for vimentin, which is a characteristic feature of ovarian fibrothecoma. Conclusion: The accurate preoperative diagnosis of ovarian fibrothecoma with cystic changes could have prevented the extensive surgical intervention such as bilateral salpingo- oopherectomy with hysterectomy.

Introdução: a leucemia mieloide aguda (LMA) caracteriza-se por mutações genéticas que afetam as células tronco de origem mieloide, resultando na proliferação descontrolada de células neoplásicas e imaturas, os blastos. Estes acumulam-se rapidamente na medula óssea, devido à alta taxa de multiplicação e interferem na hematopoiese normal de células saudáveis. As manifestações orais da LMA são comuns e podem aparecer na fase precoce da doença, sendo indispensável neste cenário o papel da equipe multidisciplinar, na qual o odontólogo pode detectar os sinais de alerta na cavidade oral, suspeitar de leucemia e encaminhar ao Hematologista. Objetivo: por meio de uma revisão integrativa da literatura, avaliar a incidência das manifestações orais como forma de diagnóstico precoce da LMA por meio da equipe multidisciplinar. Material e métodos: levantamento de artigos indexados nas bases de dados PubMed, Lilacs e Scielo a partir de 2000; por meio dos seguintes descritores: Leukemia AND oral manifestations. Primariamente, obtiveram-se 430 referências. Após aplicação dos critérios de exclusão/inclusão, restaram 26 artigos analisados no presente estudo. Resultados: a LMA, caracterizada pelo comprometimento da linhagem mieloide, é uma neoplasia mais frequente na idade adulta, porém, cerca 25% dos casos são pediátricos. Sinais e sintomas orais primários manifestam-se em aproximadamente 90% dos casos e consistem basicamente em: ulcerações, petéquias, púrpuras, sangramento oral espontâneo, hiperplasia gengival (acompanhada ou não de necrose), lábios fissurados, além de infecções oportunistas recorrentes. O grave sarcoma mieloide, um tumor extramedular sólido, surge em apenas 5% dos casos. Alguns autores destacam que pacientes com sangramentos orais ou púrpuras apresentam tempo de sobrevida reduzido em relação aos demais. Tais acometimentos também podem aparecer na leucemia crônica, porém não são específicos como na LMA. Conclusão: Em casos de LMA, as manifestações orais são muito prevalentes e de extrema importância para o diagnóstico precoce por meio da equipe multidisciplinar de saúde.