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2.
N Engl J Med ; 384(13): 1204-1215, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789009

RESUMO

BACKGROUND: Pulmonary arterial hypertension is characterized by pulmonary vascular remodeling, cellular proliferation, and poor long-term outcomes. Dysfunctional bone morphogenetic protein pathway signaling is associated with both hereditary and idiopathic subtypes. Sotatercept, a novel fusion protein, binds activins and growth differentiation factors in the attempt to restore balance between growth-promoting and growth-inhibiting signaling pathways. METHODS: In this 24-week multicenter trial, we randomly assigned 106 adults who were receiving background therapy for pulmonary arterial hypertension to receive subcutaneous sotatercept at a dose of 0.3 mg per kilogram of body weight every 3 weeks or 0.7 mg per kilogram every 3 weeks or placebo. The primary end point was the change from baseline to week 24 in pulmonary vascular resistance. RESULTS: Baseline characteristics were similar among the three groups. The least-squares mean difference between the sotatercept 0.3-mg group and the placebo group in the change from baseline to week 24 in pulmonary vascular resistance was -145.8 dyn · sec · cm-5 (95% confidence interval [CI], -241.0 to -50.6; P = 0.003). The least-squares mean difference between the sotatercept 0.7-mg group and the placebo group was -239.5 dyn · sec · cm-5 (95% CI, -329.3 to -149.7; P<0.001). At 24 weeks, the least-squares mean difference between the sotatercept 0.3-mg group and the placebo group in the change from baseline in 6-minute walk distance was 29.4 m (95% CI, 3.8 to 55.0). The least-squares mean difference between the sotatercept 0.7-mg group and the placebo group was 21.4 m (95% CI, -2.8 to 45.7). Sotatercept was also associated with a decrease in N-terminal pro-B-type natriuretic peptide levels. Thrombocytopenia and an increased hemoglobin level were the most common hematologic adverse events. One patient in the sotatercept 0.7-mg group died from cardiac arrest. CONCLUSIONS: Treatment with sotatercept resulted in a reduction in pulmonary vascular resistance in patients receiving background therapy for pulmonary arterial hypertension. (Funded by Acceleron Pharma; PULSAR ClinicalTrials.gov number, NCT03496207.).


Assuntos
Hipertensão Arterial Pulmonar/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator de Crescimento Transformador beta/antagonistas & inibidores , Resistência Vascular/efeitos dos fármacos , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Humanos , Injeções Subcutâneas , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/fisiopatologia , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Trombocitopenia/induzido quimicamente , Teste de Caminhada
3.
Pan Afr Med J ; 38: 9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33520078

RESUMO

In this paper, we report two cases of induced thrombocytopenia after the infusion of glycoprotein (GP) IIb/IIIa receptors antagonists, following a coronary angioplasty. The first patient is a 65-year-old woman, admitted with acute coronary syndrome requiring percutaneous angioplasty with stenting. The patient was given tirofiban + unfractionated heparin (UFH). Ten hours later, the patient revealed very severe thrombocytopenia and went into hemorrhagic shock (hematemesis and hematoma at the injection site). The patient was transfused with nine units of red blood cells (RBCs), 24 platelets pellets and 4 units of fresh frozen plasma (FFP). The second patient is a 76-year-old woman. She was admitted to hospital for acute coronary syndrome necessitating percutaneous angioplasty with stenting and a glycoprotein IIb/IIIa receptor antagonists, tirofiban + unfractionated (UFH). Four hours later, the patient presented with gingivorrhagia associated thrombocytopenia. She received six platelet pellets transfusion with well clinical and biological improvement. These two observations raise the significance of a close monitoring of platelet count after the initiation of GP IIb/IIIa antagonists infusion, which are sometimes responsible for life-threatening adverse events.


Assuntos
Inibidores da Agregação de Plaquetas/efeitos adversos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Trombocitopenia/induzido quimicamente , Tirofibana/efeitos adversos , Idoso , Angioplastia Coronária com Balão , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Feminino , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Plasma , Inibidores da Agregação de Plaquetas/administração & dosagem , Transfusão de Plaquetas , Trombocitopenia/terapia , Tirofibana/administração & dosagem
4.
Medicine (Baltimore) ; 100(6): e24580, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578556

RESUMO

ABSTRACT: We conducted this retrospective analysis to assess whether oral antiplatelet drugs (APDs) during radiotherapy increase bleeding risk.Patients who underwent radiotherapy for esophageal cancer (EC) in the Third Affiliated Hospital of Soochow University from January 2015 to December 2019 were screened. After the differences in clinical parameters were eliminated by a propensity-score matched (PSM) analysis at a 1:1 ratio, the thrombocytopenia, consumption of platelet-increasing drugs, suspension of radiotherapy, and bleeding in patients taking APDs were compared with those in the control group.A total of 986 patients were included in the original dataset. Of these, 34 patients took APDs during radiotherapy. After matching, the APD and control groups each retained 31 patients. There was no significant difference in platelet concentrations between the two groups before radiotherapy (P = .524). The lowest platelet concentration during radiotherapy in the APD group was significantly lower (P = .033). The consumption of platelet-increasing drugs in the APD group was higher than that in the control group (P  < .05). However, there was no significant difference in the average number of days of radiotherapy suspension because of thrombocytopenia (P = .933) and no significant difference in the incidence of bleeding between the two groups (P = .605).Oral APDs during radiotherapy lead to a further decrease in platelet concentration, but timely and adequate application of platelet-increasing drugs can avoid the increased risk of bleeding and the reduced efficacy of radiotherapy.


Assuntos
Hemorragia/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Radioterapia/efeitos adversos , Trombocitopenia/induzido quimicamente , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Am J Hematol ; 96(3): 320-329, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33326124

RESUMO

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.


Assuntos
Anafilaxia/induzido quimicamente , Anticoagulantes/efeitos adversos , Autoanticorpos/sangue , Autoantígenos/imunologia , Plaquetas/metabolismo , Heparina/efeitos adversos , Técnicas Imunoenzimáticas/métodos , Imunoglobulina G/sangue , Ativação Plaquetária/imunologia , Fator Plaquetário 4/imunologia , Serotonina/sangue , Trombocitopenia/diagnóstico , Adulto , Anticoagulantes/uso terapêutico , Autoanticorpos/imunologia , Quimioterapia Combinada , Reações Falso-Negativas , Feminino , Parada Cardíaca , Heparina/uso terapêutico , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Erros Médicos , Obesidade/complicações , Embolia Pulmonar/complicações , Embolia Pulmonar/tratamento farmacológico , Recidiva , Sensibilidade e Especificidade , Trombocitopenia/induzido quimicamente , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Varfarina/uso terapêutico
8.
Medicine (Baltimore) ; 99(42): e22793, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080751

RESUMO

RATIONALE: Thrombocytepenia, anasarca, fever, renal insufficiency, and organomegaly (TAFRO) syndrome is a novel disease entity characterized by a constellation of symptoms (thrombocytopenia, anasarca, fever, renal insufficiency, and organomegaly). Here, we describe the development of TAFRO syndrome-like features during the treatment of rheumatoid arthritis with a Janus kinase (JAK) inhibitor. PATIENT CONCERNS: In this report, a 74-year-old woman treated with a JAK inhibitor (tofacitinib) for rheumatoid arthritis was admitted because of fever and thrombocytopenia. DIAGNOSES: On laboratory examination, marked thrombocytopenia and elevated creatinine and C-reactive protein levels were present. A computed tomography scan revealed lymphadenopathy, hepato-splenomegaly, and anasarca. A left axillary lymph node biopsy revealed Castleman's disease-like features. These clinical features satisfied the proposed diagnostic criteria for TAFRO syndrome. Since autoimmune disorders should be excluded when diagnosing TAFRO syndrome, it is not strictly correct to diagnose her as TAFRO syndrome. Therefore, we diagnosed her as rheumatoid arthritis complicated by TAFRO syndrome-like features. INTERVENTIONS: The patient was treated with high-dose glucocorticoid, tacrolimus, eltrombopag, intravenous immunoglobulin, and rituximab. OUTCOMES: Her condition was refractory to the above-mentioned treatment, and she eventually died because of multi-organ failure 6 months after the first admission. LESSONS: TAFRO syndrome-like features can develop during treatment with a JAK inhibitor for rheumatoid arthritis. Patients with autoimmune diseases complicated by TAFRO syndrome-like features can follow a fatal clinical course, and thus, an intensive combined treatment is warranted for such patients, especially in cases refractory to glucocorticoid.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/induzido quimicamente , Inibidores de Janus Quinases/efeitos adversos , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Trombocitopenia/induzido quimicamente , Idoso , Evolução Fatal , Feminino , Humanos , Insuficiência de Múltiplos Órgãos/etiologia
9.
Medicine (Baltimore) ; 99(43): e22901, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120841

RESUMO

INTRODUCTION: Chemotherapeutic agents of direct cell damage play a role in initiating thrombotic microangiopathy (TMA), however still being underdiagnosed. Decitabine (DAC) is a pyrimidine analogue of the nucleoside cytidine, which can lead to injury to endothelium. Biopsy-proven DAC-induced kidney injury is rare. PATIENT CONCERNS: A 47-year-old Chinese man with membranous nephropathy presented recurrent edema and acute kidney injury after a 3-day course of low dose DAC infusion because of cyclophosphamide-relating thrombocytopenia. DIAGNOSIS: Laboratory data revealed nephrotic syndrome, hematuria, renal glycosuria and hypokalemia with hyperchloridemia. Renal pathological findings revealed TMA with secondary glomerular crescents formation (28%), partial foot process effacement and acute tubular necrosis. A diagnosis of DAC-induced renal TMA was considered. INTERVENTIONS: As DAC had been timely discontinued before admission, the patient only received supportive treatment. OUTCOMES: The patient achieved rapid remission of acute kidney injury after DAC withdrawal, and his serum creatinine further decreased to normal level after 6 months. CONCLUSION: Careful monitoring of renal function especially serum creatinine should be emphasized during DAC treatment.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Decitabina/efeitos adversos , Glomérulos Renais/patologia , Rim/patologia , Microangiopatias Trombóticas/induzido quimicamente , Lesão Renal Aguda/etiologia , Tratamento Conservador , Ciclofosfamida/efeitos adversos , Glomerulonefrite Membranosa/patologia , Humanos , Imunossupressores/efeitos adversos , Rim/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Trombocitopenia/induzido quimicamente , Suspensão de Tratamento
10.
Arq. bras. cardiol ; 115(4): 717-718, out. 2020.
Artigo em Português | LILACS, Sec. Est. Saúde SP | ID: biblio-1131352

RESUMO

Resumo Baixas doses de edoxabana e enoxaparina sódica foram objeto de uma comparação retrospectiva implementada com a técnica do escore de propensão a fim de mitigar os efeitos das diferenças nas características clínicas basais de duas coortes e minimizar o risco de viés. Posteriormente, usando um modelo de riscos proporcionais de Cox, avaliou-se a associação de cada tipo de terapia com o risco do composto de morte por todas as causas, acidente vascular cerebral/ataque isquêmico transitório, hospitalizações e ocorrência de sangramentos maiores. Para essa análise, um valor de p < 0,05 foi considerado estatisticamente significante. A terapia com enoxaparina e cirrose hepática como causadora de trombocitopenia estiveram associadas ao aumento do risco do endpoint composto (enoxaparina: hazard ratio (HR): 3,31; IC 95%: 1,54 a 7,13; p = 0,0023; cirrose hepática, HR: 1,04; 95% CI: 1,002 a 1,089; p = 0,0410). Por outro lado, a terapia com edoxabana mostrou-se significativamente associada à diminuição do risco do endpoint composto (HR: 0,071; 95% CI: 0,013 a 0,373; p = 0,0019). Com base nessa análise retrospectiva, o edoxaban em doses baixas seria uma ferramenta farmacológica segura e eficaz para a profilaxia de eventos cardioembólicos em pacientes com FA e trombocitopenia.


Abstract Low-dose edoxaban and enoxaparin sodium have been the subject of a retrospective comparison implemented with the propensity score technique in order to mitigate the effects of the differences in the basal clinical features of two cohorts and minimize the risk of bias. Subsequently, using a Cox proportional-hazards model, the association of each type of therapy with the risk of the composite of all-cause death, stroke/transient ischemic attack, hospitalizations and major bleeding events was assessed. For this analysis, a p-value < 0.05 was considered statistically significant. Therapy with enoxaparin and liver cirrhosis as causing thrombocytopenia were associated with increased risk of the composite endpoint (enoxaparin: hazard ratio (HR): 3.31; 95% CI: 1.54 to 7.13; p = 0.0023; liver cirrhosis, HR: 1.04; 95% CI: 1.002 to 1.089; p = 0.0410). Conversely, edoxaban therapy was significantly associated with decreased risk of the composite endpoint (HR: 0.071; 95% CI: 0.013 to 0.373; p = 0.0019). Based on this retrospective analysis, edoxaban at low doses would appear as an effective and safe pharmacological tool for the prophylaxis of cardioembolic events in patients with AF and thrombocytopenia.


Assuntos
Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Fibrinolíticos/efeitos adversos , Anticoagulantes/efeitos adversos
11.
Vnitr Lek ; 66(4): 242-248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972188

RESUMO

Heparin-induced thrombocytopenia (HIT) is an immunologically-mediated complication, which usually follows heparin exposition, less frequently exposition to other drugs or even occurs spontaneously. The type of heparin, its dose and mode of application as well as the exposition time, major trauma or operation, and obesity represent the main risk factors for HIT. The probability of HIT correlates with so-called 4T-score. A confirmatory laboratory diagnostic should be exclusively reserved for patients with a medium to a high probability of HIT development (more than 3 points in 4T-score). The screening method is based on serological detection of antibodies against heparin-platelet factor-4 complexes; confirmation tests aim to identify the activation of platelets. The treatment of HIT requires an immediate interruption of heparin application and rigorous antithrombotic treatment with an alternative agent. Herein authors describe a clinical case of HIT manifested as an extreme urticarial reaction in the location of nadroparin application as well as thrombosis of deep subcutaneous veins in a polymorbid obese patient with an extensive and infected burn. Due to timely diagnosis and fondaparinux treatment, no more severe thrombotic events occurred in this patient.


Assuntos
Trombocitopenia , Trombose , Anticoagulantes/efeitos adversos , Fondaparinux , Heparina/efeitos adversos , Humanos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico
13.
Orv Hetil ; 161(38): 1646-1651, 2020 09.
Artigo em Húngaro | MEDLINE | ID: mdl-32924969

RESUMO

As the topical use of non-steroidal anti-inflammatory drugs (NSAIDs) has gained popularity recently, adverse reactions related to their application have also become more common. The authors present the case of a 49-year-old man, who used etofenamate gel to treat leg pain. Following sun exposure, haemorrhagic, atypical lesions appeared and after rapid spread of the symptoms, the patient was hospitalized. In the area of the etofenamate application as well as on both legs, arms, trunk and face, confluent, erythematous sero-papules and macules were found, along with petechiae on the oral mucosa. Splenomegaly and thrombocytopenia accompanied the skin symptoms, which prompted an oncohematological workup, and the patient was diagnosed with hairy cell leukaemia. Epicutaneous testing (ET) was performed and found a positive reaction to etofenamate gel as well wood tar, propylen glycol, fragrance mix I, methylisothiazolinone, benzoic acid and balsam of Peru. The lymphocyte transformation test (LTT) and CD69 expression were negative for etofenamate. Orv Hetil. 2020; 161(38): 1646-1651.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Ácido Flufenâmico/análogos & derivados , Leucemia de Células Pilosas/diagnóstico , Esplenomegalia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Administração Cutânea , Administração Tópica , Anti-Inflamatórios não Esteroides/administração & dosagem , Ácido Flufenâmico/administração & dosagem , Ácido Flufenâmico/efeitos adversos , Humanos , Leucemia de Células Pilosas/patologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Púrpura/induzido quimicamente
15.
Medicine (Baltimore) ; 99(31): e21490, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756179

RESUMO

BACKGROUND: Whether the combination of gefitinib and chemotherapy is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of gefitinib combined with chemotherapy versus chemotherapy alone for treating advanced NSCLC. METHODS: Literature on comparing the effects of gefitinib combined with chemotherapy and chemotherapy alone in treating NSCLC was retrieved from the PubMed, EMBASE and Cochrane Database. The primary outcome measures included progression-free survival (PFS) and overall survival (OS). Revman 5.3 was used for data processing. RESULTS: Seven randomized controlled trials were included, involving a total of 1418 patients. There appeared a significant improvement in PFS (hazard ratio (HR) = 0.60 [95% CI 0.43, 0.82], P = .001) after treatment with gefitinib combined with chemotherapy when compared with chemotherapy alone. The subgroup analysis showed a significant advantage of sequential administration (HR = 0.67 [95% CI 0.57, 0.79], P < .00001). There was no significant improvement in OS (HR = 0.92 [95% CI 0.71, 1.20], P = .54), and no significant improvement in overall response rate (ORR) (HR = 0.98 [95% CI 0.67, 1.44], P = .93). The risks of rash and diarrhea (odds ratios) were higher in gefitinib combined with chemotherapy group when compared with chemotherapy alone, and there were significant differences on grade 3/4 rash and thrombocytopenia between 2 groups. CONCLUSION: Gefitinib combined with chemotherapy is superior to chemotherapy alone in PFS, sequential administration prolongs the patients' PFS, however, a survival advantage is not shown in OS or ORR. Gefitinib combined with chemotherapy aggravates rash, diarrhea and thrombocytopenia.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gefitinibe/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Exantema/induzido quimicamente , Feminino , Gefitinibe/efeitos adversos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
17.
N Engl J Med ; 383(7): 617-629, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32786187

RESUMO

BACKGROUND: Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study. METHODS: We randomly assigned previously untreated patients with confirmed AML who were ineligible for standard induction therapy because of coexisting conditions, because they were 75 years of age or older, or both to azacitidine plus either venetoclax or placebo. All patients received a standard dose of azacitidine (75 mg per square meter of body-surface area subcutaneously or intravenously on days 1 through 7 every 28-day cycle); venetoclax (target dose, 400 mg) or matching placebo was administered orally, once daily, in 28-day cycles. The primary end point was overall survival. RESULTS: The intention-to-treat population included 431 patients (286 in the azacitidine-venetoclax group and 145 in the azacitidine-placebo [control] group). The median age was 76 years in both groups (range, 49 to 91). At a median follow-up of 20.5 months, the median overall survival was 14.7 months in the azacitidine-venetoclax group and 9.6 months in the control group (hazard ratio for death, 0.66; 95% confidence interval, 0.52 to 0.85; P<0.001). The incidence of complete remission was higher with azacitidine-venetoclax than with the control regimen (36.7% vs. 17.9%; P<0.001), as was the composite complete remission (complete remission or complete remission with incomplete hematologic recovery) (66.4% vs. 28.3%; P<0.001). Key adverse events included nausea of any grade (in 44% of the patients in the azacitidine-venetoclax group and 35% of those in the control group) and grade 3 or higher thrombocytopenia (in 45% and 38%, respectively), neutropenia (in 42% and 28%), and febrile neutropenia (in 42% and 19%). Infections of any grade occurred in 85% of the patients in the azacitidine-venetoclax group and 67% of those in the control group, and serious adverse events occurred in 83% and 73%, respectively. CONCLUSIONS: In previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone. The incidence of febrile neutropenia was higher in the venetoclax-azacitidine group than in the control group. (Funded by AbbVie and Genentech; VIALE-A ClinicalTrials.gov number, NCT02993523.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Azacitidina/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Recidiva , Indução de Remissão , Sulfonamidas/efeitos adversos , Trombocitopenia/induzido quimicamente
18.
Oncology ; 98(11): 771-778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32829332

RESUMO

INTRODUCTION: Because of the increasing age of the general population, there is an increasing number of older patients with lung cancer. Cancer chemotherapy often causes severe hematological toxicity in older patients. OBJECTIVE: This study aimed to explore the risk factors affecting the hematological toxicity of cytotoxic anticancer drugs in patients with lung cancer. METHODS: Data were retrospectively collected from 194 patients with lung cancer at Niigata University Medical and Dental Hospital, Japan, between April 2011 and March 2016, when the patients underwent their first round of cytotoxic chemotherapy. The patients were divided into three groups on the basis of age: <65, 65-74, and ≥75 years. Physiological functions and laboratory data before treatment, as well as hematological adverse events following chemotherapy, were compared among the groups. RESULTS: Patients aged ≥75 years were significantly more likely to experience grade 3 or 4 neutropenia, compared with patients aged <65 years. However, there were no differences in the incidence of anemia or thrombocytopenia among the age groups. The frequency of febrile neutropenia tended to increase with age. Multivariate analysis showed that age ≥75 years, male sex, and a performance status of ≥2 were independent factors for grade 3 or 4 neutropenia. Patients with 2 or 3 of these factors had a significantly higher frequency of neutropenia, compared with patients who had 0 or 1 of these factors. CONCLUSION: We found that age ≥75 years, male sex, and a performance status of ≥2 were independent risk factors for grade 3 or 4 neutropenia.


Assuntos
Doenças Hematológicas/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Fatores Etários , Idoso , Anemia/induzido quimicamente , Neutropenia Febril/induzido quimicamente , Feminino , Doenças Hematológicas/fisiopatologia , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente
19.
Ann Hematol ; 99(8): 1771-1778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32601796

RESUMO

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1-3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia , Linfoma de Célula do Manto/terapia , Sirolimo/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Trombocitopenia/mortalidade , Vincristina/administração & dosagem , Vincristina/efeitos adversos
20.
J Investig Med High Impact Case Rep ; 8: 2324709620944091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32720827

RESUMO

COVID-19 (coronavirus disease-2019) infection is a highly prothrombotic state, resulting from a dysregulation of the coagulation cascade. Therefore, thromboprophylaxis is strongly recommended in these patients, with some experts even advocating for therapeutic dosing to prevent thromboembolic events. Heparin-induced thrombocytopenia (HIT) is a well-known complication of heparin therapy. In this article, we report a case of HIT in a patient with COVID-19. A 63-year-old male presented with 1 week of dry cough and diarrhea. He had a positive nasopharyngeal COVID-19 reverse-transcriptase-polymerase chain reaction. On admission, the platelet count and liver function tests were within normal limits. During his hospitalization, he developed a right femoral deep venous thrombosis and was started on therapeutic anticoagulation. Due to worsening respiratory failure, he was intubated and mechanically ventilated. Between days 11 and 12 of hospitalization, platelet count dropped from 304 000 to 96 000 cells/µL. He had a high pretest probability for HIT with a 4T score of 6 and a positive anti-PF4/heparin antibody. Heparin drip was discontinued and was switched to argatroban. The serotonin release assay eventually returned positive, which confirmed the diagnosis of HIT. We also discuss potential overdiagnosis of HIT in COVID-19 through 4 cases with false-positive HIT antibodies.


Assuntos
Anticoagulantes/efeitos adversos , Infecções por Coronavirus/complicações , Heparina/efeitos adversos , Pneumonia Viral/complicações , Trombocitopenia/induzido quimicamente , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Betacoronavirus , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Pandemias
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