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INTRODUCTION: CMML is a rare neoplasm with overlapping myelodysplastic and myeloproliferative features whose only potential cure is allogeneic hematopoietic cell transplantation (allo-HCT). METHODS: This retrospective study examined 27 CMML patients with high-risk clinical features who underwent first allo-HCT at our institution between 2004 and 2022. RESULTS: Nineteen patients were diagnosed with the proliferative subtype (CMML-MPN) and 8 with the dysplastic subtype (CMML-MDS). Median OS was 15 months post-HCT (95% CI: 5-71); OS at 1, 3, and 5 years was 52%, 35%, and 35%, respectively. Compared to those with CMML-MPN, patients with CMML-MDS had longer OS (median, 8.6 vs. 0.9 years; p = 0.025), RFS (4.4 vs. 0.5 years; p = 0.021), and GVHD-free, relapse-free survival (GRFS, 9.4 vs. 3.4 months; p = 0.033) as well as lower 1-year NRM (13 vs. 47%; p = 0.043), with the statistical significance of this CMML subtype effect maintained in multivariable models. High-risk cytogenetics were associated with shorter GRFS in the univariable (median, 3.1 vs. 6.2 months; p = 0.013) and multivariable (HR = 4.88; p = 0.006) settings. CONCLUSIONS: Patients who underwent transplant for CMML-MDS experienced substantially better outcomes than those transplanted for CMML-MPN. Future studies are needed for transplantation optimization in CMML, especially CMML-MPN.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. RESULTS: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (Pâ =â .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6â ±â 0.3 vs -2.6â ±â 0.4, Pâ =â .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (Pâ =â .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, Pâ =â .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group. CONCLUSION: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT04579393.
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Tratamento Farmacológico da COVID-19 , Adulto , Aminopiridinas , Método Duplo-Cego , Hospitalização , Humanos , Morfolinas , Oxazinas/uso terapêutico , Oxigênio , Piridinas/uso terapêutico , Pirimidinas , SARS-CoV-2 , Resultado do TratamentoRESUMO
BACKGROUND: Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion-related major morbidity and mortality. Diagnosing TACO is difficult because there are no pathognomonic signs and symptoms. TACO biomarkers may aid in diagnosis, decrease time to treatment, and differentiate from other causes of posttransfusion dyspnea such a transfusion-related acute lung injury. STUDY DESIGN AND METHODS: A systematic review of literature was performed in EMBASE, PubMed, the TRIP Database, and the Cochrane Library, from inception to June 2018. All articles discussing diagnostic markers for TACO were included. Non-English articles or conference abstracts were excluded. RESULTS: Twenty articles discussing biomarkers for TACO were included. The majority investigated B-type natriuretic peptide (BNP) and the N-terminal prohormone cleavage fragment of BNP (NT-proBNP), markers of hydrostatic pressure that can be determined within 1 hour. The data indicate that a post/pretransfusion NT-proBNP ratio > 1.5 can aid in the diagnosis of TACO. Posttransfusion levels of BNP less than 300 or NT-proBNP less than 2000 pg/mL, drawn within 24 hours of the reaction, make TACO unlikely. Cut-off levels that exclude TACO are currently unclear. In critically ill patients, the specificity of natriuretic peptides for circulatory overload is poor. Other biomarkers, such as cytokine profiles, cannot discriminate between TACO and transfusion-related acute lung injury. CONCLUSION: Currently, BNP and NT-proBNP are the primary diagnostic biomarkers researched for TACO. An NT-proBNP ratio greater than 1.5 is supportive of TACO, and low levels of BNP or NT-proBNP can exclude TACO. However, they are unreliable in critically ill patients. Other biomarkers, including cytokines and pulmonary edema fluid-to-serum protein ratio have not yet been sufficiently investigated for clinical use.
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Transfusão de Sangue , Dispneia/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Edema Pulmonar/sangue , Reação Transfusional/sangue , Estado Terminal , Dispneia/etiologia , Feminino , Humanos , Masculino , Edema Pulmonar/etiologiaRESUMO
IMT504 is a novel immunomodulatory oligonucleotide that has shown immunotherapeutic properties in early preclinical and clinical studies. IMT504 was tested in a neutropenic rat model of Pseudomonas aeruginosa bacteremia and sepsis. This animal system recapitulates many of the pathological processes found in neutropenic patients with Gram-negative, bacterial infections. The research was conducted in the setting of an academic research laboratory. The test subjects were Sprague-Dawley rats. Animals were rendered neutropenic by administration of cyclophosphamide, colonized with P. aeruginosa by oral feeding, and then randomized to receive IMT504 over a range of doses and treatment regimens representing early and late therapeutic interventions. IMT504 immunotherapy conferred a significant survival advantage over the 12-day study period compared with the results seen with placebo-treated animals when the therapy was administered at the onset of neutropenia and even in the absence of antibiotics and after the onset of fever and systemic infection. Notably, even late salvage IMT504 monotherapy was highly effective (13/14 surviving rats with IMT504 therapy versus 2/14 controls, P=<0.001). Moreover, late salvage IMT504 monotherapy was as effective as antibiotic therapy (13/14 surviving rats versus 21/21 rats, P=0.88). In addition, no antagonism or loss of therapeutic efficacy was noted with combination therapy of IMT504 plus antibiotics. IMT504 immunotherapy provides a remarkable survival advantage in bacteremia and sepsis in neutropenic animals and deserves further study as a new treatment option in patients with, or at risk for, severe Gram-negative bacterial infections and sepsis.
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Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Neutropenia/tratamento farmacológico , Oligodesoxirribonucleotídeos/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Sepse/microbiologia , Sepse/prevenção & controle , Animais , Feminino , RatosRESUMO
Previous studies have reported higher recurrence rates in T1a/b N0 breast cancers characterized by high-risk biology (HER2+ or triple-negative), but the benefits of adjuvant chemotherapy in these patients have not been established. This study was designed to determine whether recurrence risk is reduced with chemotherapy and to define a group of patients most appropriate for treatment based on retrospective data. We pooled cases from two multi-institutional databases spanning the period of 1996-2010. A propensity score model adjusted unbalanced confounders between the groups treated or untreated with adjuvant chemotherapy and, in case of HER2-positive disease, with trastuzumab. Competing risk analysis was utilized to study effects of chemotherapy on cancer recurrences in the matched populations. Among the 318 patients identified, 41 % received adjuvant chemotherapy and 54 % of HER2+ patients received it with trastuzumab. The cumulative risk of recurrence at 5 years was 7.3 %. Age less than 35 years and triple-negative status were the only significant prognostic factors. Overall, administration of chemotherapy was not associated with a significant decrease in the risk of recurrence (HR 0.93, p = 0.91). The rate of recurrence in HER2+ patients who received trastuzumab was lower but not statistically significant (HR 0.50, p = 0.63). Clinical characteristics are of limited prognostic value for stratifying risk of recurrence in very small, node-negative HER2+, or triple-negative cancers. While limited by the small number of events, our analysis does not support the increasingly prevalent practice of administering adjuvant chemotherapy in this population without more accurate prognostic and predictive factors.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Receptor ErbB-2/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Recidiva , Estudos Retrospectivos , TrastuzumabRESUMO
ABSTRACT: Myelodysplastic syndromes (MDSs) are characterized by a clonal proliferation of hematopoietic stem cells with potential life-threatening cytopenia(s) and transformation to acute myeloid leukemia. Individualized risk stratification is evolving with new molecular models, such as the Molecular International Prognostic Scoring System, for better estimation of leukemic transformation and overall survival. The only potential cure for MDSs is allogeneic transplant, although it is underutilized in MDSs because of advanced patient age and multiple comorbidities. Optimization of transplant relies on improved identification of high-risk patients pretransplant, using targeted therapies leading to deeper molecular response, developing lower toxicity conditioning regimens, engineering better molecular tools for early detection and relapse monitoring, and adding maintenance treatment strategies for high-risk patients posttransplant. This review provides an overview of transplant in MDSs with updates, future directions, and role for novel therapies.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndromes Mielodisplásicas/terapia , Leucemia Mieloide Aguda/terapia , Transplante Homólogo , Recidiva , Condicionamento Pré-TransplanteRESUMO
A molecular scoring system (IPSS-M) was recently proposed for myelodysplastic syndrome (MDS). We conducted a retrospective study of adults with MDS referred 2019-2021. The primary outcomes were leukemia-free survival (LFS) and overall survival (OS). One hundred and forty-four patients diagnosed between 2011 and 2021 were analyzed. After IPSS-M re-stratification, 33% of patients were up-staged and 11% down-staged. Median follow-up was 2.8 years and 53 patients died (37%). Cumulative incidence of acute myeloid leukemia (AML) transformation was 20% at 3 years post-diagnosis. International Prognostic Scoring System (IPSS), revised version (IPSS-R) was significantly associated with LFS (log-rank p = 9.2e-05; 'very high' vs. 'low' risk HR = 3.85, p = 5.8e-04) and OS (log-rank p = 7.2e-06; 'very high' vs. 'low' HR = 5.09, p = 1.7e-04). IPSS-M was also a significant predictor of LFS (log-rank p = 1.1e-06; 'very high' vs. 'low' HR = 4.97, p = 2.2e-05) and OS (log-rank p = 4.8e-07; 'very high' vs. 'low' HR = 6.42, p = 2.5e-05) while providing better discrimination than IPSS-R for both outcomes. This mutation-incorporating prognostic index has greater discriminative potential than IPSS-R to predict AML transformation and any-cause mortality.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Humanos , Estudos Retrospectivos , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/genética , Prognóstico , Risco , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/genéticaRESUMO
Anemia after allogeneic hematopoietic stem cell transplantation (HSCT) can be immune or non-immune mediated. Auto- or alloimmunity resulting from blood group incompatibility remains an important cause in post-HSCT immune-mediated anemia. ABO incompatibility is commonly encountered in HSCT and may lead to serious clinical complications, including acute hemolysis, pure red cell aplasia, and passenger lymphocyte syndrome. It remains controversial whether ABO incompatibility may affect HSCT outcomes, such as relapse, nonrelapse mortality, graft-versus-host disease, and survival. Non-ABO incompatibility is less frequently encountered but can have similar complications to ABO incompatibility, causing adverse clinical outcomes. It is crucial to identify the driving etiology of post-HSCT anemia in order to prevent and treat this condition. This requires a comprehensive understanding of the mechanism of anemia in blood group-incompatible HSCT and the temporal association between HSCT and anemia. In this review, we summarize the literature on post-HSCT immune-mediated anemia with a focus on ABO and non-ABO blood group incompatibility, describe the underlying mechanism of anemia, and outline preventive and treatment approaches.
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Anemia Hemolítica Autoimune , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Aplasia Pura de Série Vermelha , Sistema ABO de Grupos Sanguíneos , Anemia Hemolítica Autoimune/complicações , Incompatibilidade de Grupos Sanguíneos/complicações , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , HumanosRESUMO
For 30 years, transfusion-associated circulatory overload (TACO) has been recognized as a serious transfusion complication. Currently, TACO is the leading cause of transfusion-related morbidity and mortality worldwide which occurs in 1% to 12% of at-risk populations. Despite an incomplete understanding of the underlying pathophysiology, TACO is defined as a collection of signs and symptoms of acute pulmonary edema due to circulatory overload occurring within 6 to 12â¯hours of transfusion. In the past decade, large observational cohort studies resulted in better insight into the associated transfusion risk factors leading to the development of TACO. In this clinical review, we critically analyze the pathogenesis of TACO, associated risk factors, clinical presentation, diagnostic modalities, and treatment options to guide clinicians with early detection of this syndrome and intervention to improve clinical outcomes. Future research should focus on better understanding of the pathogenesis to help advance the field of volume kinetics and endothelial barrier function.
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Transfusão de Eritrócitos/efeitos adversos , Reação Transfusional/diagnóstico , Reação Transfusional/terapia , Algoritmos , Biomarcadores , Transfusão de Sangue , Bases de Dados Factuais , Mortalidade Hospitalar , Humanos , Cooperação do Paciente , Modelos de Riscos Proporcionais , Edema Pulmonar/prevenção & controle , Fatores de Risco , Reação Transfusional/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors. METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material were selected for PD-L1 IHC analysis using clone E1L3N. PD-L1 expression was evaluated using the combined positive score (CPS). Retrospective chart review was performed. We evaluated the incidence and prognostic value of PD-L1 expression in ESCC at our institution. RESULTS: Twelve out 34 cases (35%) had PD-L1 CPS scores ≥1. Ten cases had CPS scores ranging 1-5, whereas 2 cases had CPS scores > 80. The overall response rate to the standard chemotherapy with/without radiotherapy in the PD-L1 positive group was 80% versus 67% for the PDL-1 negative group (p-value 0.67). The median overall survival for the PD-L1 positive group, regardless of stage, was 11.5 months versus 7 months for PD-L1 negative group (p-value 0.34). Patients with limited stage disease with positive PD-L1 had a median survival of 53 months compared to 15 months for patients with PD-L1 negative limited stage (p-value 0.80). CONCLUSIONS: This study showed that at least one third of our ESCC tissue samples expressed PD-L1. There was a trend for higher response rates to the standard chemotherapy with/without radiotherapy and improved survival in PD-L1 positive patients. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients.
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Antígeno B7-H1/uso terapêutico , Carcinoma de Células Pequenas/imunologia , Imuno-Histoquímica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/farmacologia , Carcinoma de Células Pequenas/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
BACKGROUND: Recurrent somatic mutations in SF3B1 have been identified in patients with myelodysplastic syndromes (MDS) and are associated with ring sideroblasts (RS) and relatively favorable clinical outcomes. The 2016 World Health Organization classification categorizes patients with ≥ 5% RS and SF3B1 mutation as MDS-RS, in contrast to its prior MDS-RS classification (≥ 15% RS, no genotyping data). Treatment responses in MDS patients with mutated SF3B1 are not well described. PATIENTS AND METHODS: Patients with MDS and known SF3B1 mutational status were identified from MDS Clinical Research Consortium institutions and grouped when possible as 5% to 15% or ≥ 15% RS. Patients with wild-type versus mutated SF3B1 were matched 2:1 to analyze treatment response. RESULTS: Of 471 patients identified, 16% showed SF3B1 mutation. More patients with mutated SF3B1 were lower-risk MDS. We found that 50% were RS-positive compared to 19% of wild-type patients (P < .001). Having the mutation was associated with better overall survival (hazard ratio = 0.48, P = .001) and longer leukemia-free survival (hazard ratio = 0.5, P < .005). Patients with RS and the mutation had the best outcome. Regarding treatment response, 14 (35%) of 40 erythroid-stimulating agent-treated patients with mutation experienced response versus 9 (16%) of 56 wild-type patients (P = .032), with no differences in response to hypomethylating agents or lenalidomide. CONCLUSION: SF3B1 mutations in MDS are commonly associated with RS and show better outcomes, with mutated/positive RS presence being significantly better than isolated RS or presence of mutation or neither. Patients with mutation showed better responses to an erythroid-stimulating agent. A new categorization incorporating SF3B1 mutation status, regardless of RS percentage, shows clinical value.
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Biomarcadores Tumorais/genética , Eritroblastos/patologia , Mutação , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Fosfoproteínas/genética , Fatores de Processamento de RNA/genética , Idoso , Antineoplásicos/uso terapêutico , Eritroblastos/efeitos dos fármacos , Feminino , Predisposição Genética para Doença , Fármacos Hematológicos/uso terapêutico , Humanos , Masculino , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Fenótipo , Intervalo Livre de Progressão , Fatores de Risco , Fatores de TempoRESUMO
We evaluated the association of baseline prognostic factors with conditional net survival among survivors of six subtypes non-Hodgkin lymphoma using the SEER program data from 2000-2012. Among 2-year survivors, further prognosis markedly improved in Burkitt's (BL) and diffuse large B-cell lymphoma (DLBCL), and became the same as for follicular lymphoma (5-year net survival ≥ 85%). Mantle cell lymphoma (MCL) demonstrated the worst prognosis of all studied histologies up to 5 years of survivorship. Age and stage lost prognostic significance in BL within 2 years from diagnosis. Racial disparities in net survival disappeared within 2 years for all subtypes, except in chronic lymphocytic leukemia, where black patients had persistently worse prognosis, and in MCL, where they had unexpectedly better prognosis than other races after 2 years. Many baseline factors may lose their initial prognostic value for lymphoma survivors, which should be considered when counseling patients about their prognosis and long-term surveillance.
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Linfoma não Hodgkin/mortalidade , Vigilância da População , Sobreviventes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Adulto JovemRESUMO
The greatest challenge in treating acute myeloid leukemia (AML) is refractory disease. With approximately 60-80% of AML patients dying of relapsed disease, there is an urgent need to define and target mechanisms of drug resistance. Unfortunately, targeting cell-intrinsic resistance has failed to improve clinical outcomes in AML. Emerging data show that cell-extrinsic factors in the bone marrow microenvironment protect and support AML cells. The vascular niche, in particular, regulates AML cell survival and cell cycling by both paracrine secretion and adhesive contact with endothelial cells. Moreover, AML cells can functionally integrate within vascular endothelia, undergo quiescence, and resist cytotoxic chemotherapy. Together, these findings support the notion of blood vessels as sanctuary sites for AML. Therefore, vascular targeting agents may serve to remit AML. Several early phase clinical trials have tested anti-angiogenic agents, leukemia mobilizing agents, and vascular disrupting agents in AML patients. In general, these agents can be safely administered to AML patients and cardiovascular side effects were reported. Response rates to vascular targeting agents in AML have been modest; however, a majority of vascular targeting trials in AML are monotherapy in design and indiscriminate in patient recruitment. When considering the chemosensitizing effects of targeting the microenvironment, there is a strong rationale to build upon these early phase clinical trials and initiate phase IB/II trials of combination therapy where vascular targeting agents are positioned as priming agents for cytotoxic chemotherapy.
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Inibidores da Angiogênese/uso terapêutico , Medula Óssea/irrigação sanguínea , Células Endoteliais/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Microambiente Tumoral , Inibidores da Angiogênese/efeitos adversos , Animais , Resistencia a Medicamentos Antineoplásicos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Comunicação Parácrina/efeitos dos fármacos , Recidiva , Transdução de Sinais/efeitos dos fármacosRESUMO
We assessed practice patterns and the impact of systemic adjuvant therapy on human epidermal growth factor receptor 2 (HER2)-positive or triple-negative, node-negative breast cancers up to 10 mm in size. Records of 161 patients identified among 1415 cases diagnosed in our institutions between 2000 and 2010 were assessed for factors associated with recommendation for chemotherapy and survival outcomes. Adjuvant chemotherapy was recommended in 53% of patients, more commonly in patients with younger age, stage T1b, high grade, HER2+/ER- status and diagnosis after 2006. With a median follow-up of 54 months, the 5-year cumulative incidence of recurrence was 5.3% and overall survival was 93.2%. Age less than 40 and presence of lymphovascular invasion (LVI) were associated with higher risk of recurrence. In a univariate analysis administration of adjuvant chemotherapy was not associated with a significantly better recurrence rate (P = 0.33).
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/patologia , Padrões de Prática Médica , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/patologia , Neoplasias da Mama/química , Quimioterapia Adjuvante/tendências , Feminino , Humanos , Vasos Linfáticos/patologia , Mastectomia Segmentar , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
We report the case of a 37-year old man presenting with a left ventricular cardiac thrombus in the setting of subclinical paroxysmal nocturnal hemoglobinura (PNH) developing two years after immunosuppressive therapy for thymoma-associated aplastic anemia. The literature regarding the interplay between autoimmunity and immunosuppression, aplastic anemia, thymoma and the emergence of PNH is reviewed.