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1.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 892-896, 2020 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-33047725

RESUMO

OBJECTIVE: To measure the level of serum Semaphorin 3A (Sema3A) and to analyze the relationship between serum Sema3A and systemic lupus erythematosus (SLE) with thrombocytopenia. METHODS: The concentration of serum Sema3A was detected by enzyme-linked immuno sorbent assay (ELISA) in 170 SLE patients, 50 Sjögren's syndrome (SS) patients, 19 hypersplenism (HS) patients and 150 healthy controls (HC). Based on the presence of thrombocytopenia and whether the thrombocytopenia was in remission, the SLE patients were divided into three groups: SLE with thrombocytopenia (41 cases), SLE with thrombocytopenia remission (28 cases), and SLE without thrombocytopenia (101 cases). According to whether there was thrombocytopenia, the SS patients were divided into SS with thrombocytopenia (18 cases) and SS without thrombocytopenia (32 cases). The 28 SLE patients who underwent bone marrow aspiration biopsy were divided into two groups from the aspect of whether the bone marrow hyperplasia was normal (19 cases) or low (9 cases), as well as from the aspect of whether the maturity disturbance of megakaryocyte was positive (8 cases) or negative (20 cases). The serum Sema3A levels in SLE, SS, HS with HC were compared, meanwhile, the correlation between serum Sema3A level and platelet (PLT) in the patients with different diseases analyzed. RESULTS: (1) Serum Sema3A levels in SLE were significantly lower than in HC [(3.84±2.76) µg/L vs. (6.96±2.62) µg/L, P < 0.001], serum Sema3A levels in SS were also obviously lower than in HC [(4.35±3.57) µg/L vs. (6.96±2.62) µg/L, P < 0.001], and in HS it was lower than HC at a certain extant [(5.67±2.26) µg/L vs. (6.96±2.62) µg/L, P=0.041]. (2) Serum Sema3A levels in SLE were slightly lower than in SS, but there was no significant difference [(3.84±2.76) µg/L vs. (4.35±3.57) µg/L, P=0.282]. However, when compared with HS, serum Sema3A levels in SLE were significantly lower [(3.84±2.76) µg/L vs. (5.67±2.26) µg/L, P=0.006]. (3) Serum Sema3A concentration in SLE with thrombocytopenia was significantly lower than in SLE with thrombocytopenia remission [(1.28±1.06) µg/L vs. (3.83±2.65) µg/L, P < 0.001], and in SLE patients without thrombocytopenia [(1.28±1.06) µg/L vs. (4.87±2.60) µg/L, P < 0.001]. There was no significant difference between SLE with thrombocytopenia remission and SLE without thrombocytopenia [(3.83±2.65) µg/L vs. (4.87±2.600 µg/L, P=0.123]. Serum Sema3A concentration in SLE with thrombocytopenia was slightly lower than in SS with thrombocytopenia, but there was no significant difference [(1.28±1.06) µg/L vs. (1.68±1.11) µg/L, P=0.189]. (4) Strong positive correlations were found between serum Sema3A and PLT in SLE (r=0.600, P < 0.001). Positive correlations were also found between serum Sema3A and PLT in SS (r=0.573, P < 0.001). However, there was no such correlation showed in HS patients (P=0.393). (5) There was no significant difference of serum Sema3A concentration in SLE whether the bone marrow hyperplasia was normal or low. And the same situation appeared in the patients whether the maturity disturbance of megakaryocyte was positive or negative (P>0.05). CONCLUSION: Serum Sema3A was significantly reduced in SLE patients, and it was highly correlated with the blood damage. Similar conclusions could be drawn in patients with SS. The serum level of Sema3A was generally decreasing in desmosis which merged thrombocytopenia, and was obviously positive correlated with platelet counts.


Assuntos
Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Trombocitopenia , Ensaio de Imunoadsorção Enzimática , Humanos , Lúpus Eritematoso Sistêmico/complicações , Semaforina-3A , Trombocitopenia/etiologia
2.
Ther Umsch ; 77(8): 379-384, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-33054644

RESUMO

Thrombocytopenia as an incidental finding Abstract. Platelets play an important role in normal hemostasis and their number in the periphereal blood is normally very stable. Thrombocytopenia is frequently encountered in the clinic. As a first step, one has to exclude so called pseudothrombocytopenia due to preanalytic (EDTA as an anticoagulant) conditions. This can be done by determination of platelet counts in citrate or alternative (e. g. Thrombo-Exact) tubes or by performing a blood smear, where platelets are seen clumped. A blood smear is also the mainstay of further work-up as the differential diagnosis is very broad. In bleeding patients early therapeutic interventions have to be considered. Further work-up should be done stepwise and in collaboration with a hematologist. A definite diagnosis is essential in order to define specific therapeutic interventions, mainly in bleeding patients, in patients scheduled for surgery or patients taking antiaggregation and / or anticoagulation therapy.


Assuntos
Achados Incidentais , Trombocitopenia , Anticoagulantes/uso terapêutico , Ácido Edético , Humanos , Contagem de Plaquetas , Trombocitopenia/diagnóstico
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(8): 947-952, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32912408

RESUMO

OBJECTIVE: To analyze the difference of immune damage between patients with severe fever with thrombocytopenia syndrome (SFTS) and patients with tsutsugamushi disease. METHODS: A prospective case-control study was conducted. Thirty-one patients with SFTS and 16 patients with tsutsugamushi disease admitted to the First Affiliated Hospital of Anhui Medical University from October 2014 to June 2017 were enrolled, and another 10 healthy people were enrolled as control. The counts of CD4+ and CD8+ T lymphocytes, and the proportion of CD3+ T lymphocytes, natural kill cells (NK cells), B lymphocytes and plasma cells were detected by flow cytometry. Thirty-four inflammatory mediators were determined by a multiplex Luminex® system synchronously. The differences of lymphocytes and cytokines between the two groups were compared. RESULTS: The proportion of CD3+ T lymphocytes, the counts of CD4+ and CD8+ T lymphocytes in SFTS patients were significantly lower than those in patients with tsutsugamushi disease (t values were 4.860, 9.411 and 5.030, respectively, all P < 0.01), and the proportion of NK cells and B lymphocytes were significantly higher than those in patients with tsutsugamushi disease (t values were 2.344 and 5.896, respectively, both P < 0.05). The proportion of plasma cells in peripheral blood of SFTS patients was (7.7±1.2)%, the highest proportion of plasma cells in severe SFTS patients was up to 30%, and all patients showed λ monoclonal cell group in plasma cells. No plasma cells were detected in tsutsugamushi disease patients. The abnormal expressions of interleukin-1 receptor antibody (IL-1RA), interleukin (IL-6, IL-15, IL-10, IL-8), tumor necrosis factor-α (TNF-α), γ-interferon (IFN-γ), granulocyte colony-stimulating factor (G-CSF), eosinophil chemotactic factor (Eotaxin), IFN-γ-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP-1α, MIP-1ß), platelet-derived growth factor (PDGF-AA, PDGF-AB/BB), activated regulatory normal T cells and secretion factors (RANTES) were found in patients with SFTS and tsutsugamushi disease. The levels of IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, Eotaxin, IL-8, IP-10, MCP-1 and MIP-1α in SFTS patients were significantly higher than those in patients with tsutsugamushi disease (Z values were 2.312, 2.447, 3.660, 5.444, 1.965, 2.402, 2.402, 2.997, 3.525, 2.481, 3.817, and 2.211, respectively, all P < 0.05), while PDGF-AA, PDGF-AB/BB and RANTES were significantly lower than those in patients with tsutsugamushi disease (Z values were 3.728, 2.514, 2.649, respectively, all P < 0.05). Correlation analysis showed that RANTES, PDGF-AA and PDGF-AB/BB levels were significantly positively correlated with the level of platelet in patients with SFTS and tsutsugamushi disease (SFTS: r values were 0.223, 0.365, 0.330; tsutsugamushi disease: r values were 0.263, 0.632, 0.407, respectively, all P < 0.05). In SFTS patients, compared with the survival group (n = 21), the CD3+ and CD4+ T lymphocytes in the death group (n = 10) significantly decreased, while the plasma cells significantly increased (t values were 3.980, 3.314 and 26.692, respectively, all P < 0.01); IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, Eotaxin, IL-8, IP-10, MCP-1, MIP-1α and MIP-1ß significantly increased, while PDGF-AA, PDGF-AB/BB and RANTES significantly decreased (Z values were 3.930, 4.014, 2.832, 3.592, 2.958, 3.508, 2.578, 3.254, 4.270, 3.465, 2.663, 3.085, 3.107, 3.639, 3.043 and 3.825, respectively, all P < 0.05). CONCLUSIONS: The immune function was impaired more seriously in SFTS patients than that in tsutsugamushi disease patients. Excessive humoral immunity and apoptosis of T lymphocytes are closely related to the death in SFTS patients. The detection of CD4 cells, plasma cells and proinflammatory and anti-inflammatory cytokines (e.g. IL-6, IL-10) had great clinical significance for the differentiation and illness evaluation in disease with SFTS or tsutsugamushi disease.


Assuntos
Phlebovirus , Tifo por Ácaros , Trombocitopenia , Estudos de Casos e Controles , Humanos , Estudos Prospectivos
4.
Medicine (Baltimore) ; 99(39): e22299, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991435

RESUMO

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a condition characterized by a hyperinflammatory state and persistent macrophage activation, resulting in reactive phagocytosis of the hematopoietic elements. In children, it is usually a hereditary disorder, while in adults it is usually acquired secondary to viral infections, collagenoses, or tumors. Although accounting for 10% of hematologic malignancies, HLH is rarely associated with multiple myeloma (MM) and other plasmacytic dyscrasias. PATIENT CONCERNS: A 64-year-old Brazilian man seeked medical care with a 3-month history of intermittent fever, weight loss, night sweats, and progressive anemic symptoms. DIAGNOSIS: Total blood count showed severe bicytopenia (normocytic-normochromic anemia and thrombocytopenia), biochemical exams showed elevation of creatinine, as well as monoclonal peak in serum protein electrophoresis, high IgA dosage, and serum immunofixation with IgA kappa paraprotein. Bone marrow biopsy showed 30% of monoclonal and phenotypically anomalous plasmocytes, confirming the diagnosis of MM. Diagnosis of HLH was established by the presence of clinical and laboratory criteria: fever, splenomegaly, cytopenias, hypofibrinogenemia, hyperferritinemia, elevation of triglycerides, and several figures of erythrophagocytosis in bone marrow aspirate. INTERVENTIONS: The patient experienced pulse therapy with methylprednisolone for hemophagocytic lymphohistiocytosis, followed by initial therapy for multiple myeloma with cyclophosphamide and dexamethasone. OUTCOMES: Once the diagnosis of MM and secondary hemophagocytic syndrome was established, the patient had a rapid clinical deterioration despite the established therapeutic measures, evolving with cardiovascular failure, acute liver failure, acute disseminated intravascular coagulation, worsening renal dysfunction requiring dialysis support, respiratory dysfunction, and lowering of consciousness, characterizing rapid multiple organ dysfunction, ultimately leading to the death of the patient. INNOVATION: Here, we aimed to describe the sixth reported case of HLH associated with MM, according to cases cataloged in the PubMed database, and the first case evaluated by 18-fluordeoxyglucose positron emission tomography (18-FDG-PETCT). CONCLUSION: Our case report seeks to provide support for a better clinical and laboratory characterization of this rare paraneoplastic entity associated with MM, and aims to call the attention of hematologists and intensivists to this condition that falls within the scope of the differential diagnosis of rapid onset multiple organ failure in patients with plasmacytic neoplasms.


Assuntos
Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Anemia/sangue , Anemia/etiologia , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Medula Óssea/patologia , Brasil/epidemiologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Quimioterapia Combinada , Evolução Fatal , Febre/diagnóstico , Febre/etiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Insuficiência de Múltiplos Órgãos/complicações , Paraproteinemias/sangue , Plasmócitos/patologia , Esplenomegalia/diagnóstico , Esplenomegalia/etiologia , Trombocitopenia/sangue , Trombocitopenia/etiologia , Perda de Peso
5.
Yonsei Med J ; 61(10): 851-859, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975059

RESUMO

PURPOSE: Thrombocytopenia (platelet count <150×10³/µL) is associated with poor outcomes in various critical illness settings. However, the prognostic value of platelet count in patients with cardiogenic shock (CS) remains unclear. MATERIALS AND METHODS: We enrolled 1202 patients between January 2014 and December 2018 from a multicenter retrospective-prospective cohort registry of CS. Clinical characteristics and treatment outcomes were compared between the patients with and without thrombocytopenia. RESULTS: At presentation with CS, 244 (20.3%) patients had thrombocytopenia. The patients with thrombocytopenia had lower blood pressure, hemoglobin level, and worse liver and renal functions compared to the patients without. During hospitalization, the patients with thrombocytopenia had more frequent gastrointestinal bleeding (10.5% vs. 3.8%, p=0.009), sepsis (8.3% vs. 2.6%, p=0.013), requirement of renal replacement therapy (36.5% vs. 18.9%, p<0.001), requirement of mechanical ventilation (65.2% vs. 54.4%, p=0.003), longer intensive care unit stay (8 days vs. 4 days, p<0.001), and thirty-day mortality (40.2% vs. 28.5%, p<0.001) compared to those without. In addition, the platelet count was an independent predictor of 30-day mortality (per 103/µL decrease; adjusted hazard ratio: 1.002, 95% confidence interval: 1.000-1.003, p=0.021). CONCLUSION: Thrombocytopenia at CS presentation was associated with worse clinical findings, higher frequencies of complications, and longer stay at the intensive care unit. Also, thrombocytopenia was independently associated with increased 30-day mortality. (Clinical trial registration No. NCT02985008).


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Choque Cardiogênico , Trombocitopenia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Estado Terminal , Feminino , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Contagem de Plaquetas , Prevalência , Prognóstico , Estudos Prospectivos , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Sepse/sangue , Sepse/epidemiologia , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Trombocitopenia/diagnóstico , Trombocitopenia/mortalidade , Trombocitopenia/terapia , Resultado do Tratamento
6.
Adv Clin Exp Med ; 29(9): 1051-1056, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32946685

RESUMO

BACKGROUND: Platelets are key players in hemostasis. These blood cells contain different types of granules. Recently, there has been a growing interest in the role of inorganic polyphosphate (polyP) structures stored in dense granules of platelets and secreted during platelet activation. OBJECTIVES: To measure platelet polyP levels in patients with thrombocytopenia and thrombocythemia, and to examine the relationship of this indicator with platelet aggregation. MATERIAL AND METHODS: The study included 36 patients with hematological disorders (26 with primary chronic thrombocytopenia and 10 with essential thrombocythemia (ET)) and 40 healthy subjects. Platelet reactivity was measured using whole blood impedance aggregometry. The polyP levels were isolated from lysed platelets, which were obtained from citrated platelet-rich plasma. The procedure included inactivating endogenous phosphatases, removing phosphate units derived from DNA and proteins, and finally hydrolyzing them into monophosphate units. A colorimetric assay using malachite green and ammonium molybdate was performed in order to quantify polyP levels. RESULTS: The polyP concentrations were significantly higher in the patients with thrombocytopenia than in the patients with thrombocythemia or the controls. The polyP level was not correlated with the level of aggregation. CONCLUSIONS: The higher polyP levels observed in the patients with low platelet counts may indicate the existence of a compensatory mechanism that prevents excessive bleeding in such patients. Our study provides evidence of an essential role of polyP in platelet function and the coagulation process.


Assuntos
Plaquetas , Trombocitopenia , Hemostasia , Humanos , Ativação Plaquetária , Polifosfatos
7.
BMJ Case Rep ; 13(9)2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933915

RESUMO

The SARS-CoV-2 infection has caused a pandemic with a case rate of over 290 000 lab-confirmed cases and over 40 000 deaths in the UK. There is little evidence to inform the optimal management of a patient presenting with new or relapsed acute idiopathic thrombocytopaenic purpura with concurrent SARS-CoV-2 infection. We present a case of severe thrombocytopaenia complicated by subdural haematoma and rectal bleed associated with COVID-19. A 67-year-old man, admitted with a non-productive cough and confusion, was found to be positive for COVID-19. Ten days after admission, his platelets decreased from 146×109/L to 2×109/L. His platelets did not increase despite receiving frequent platelet transfusions. He was non-responsive to corticosteroids and intravenous immunoglobulins. Romiplostim and eltrombopag were given and after 9 weeks of treatment, his platelet count normalised. He was deemed medically fit with outpatient follow-up in a haematology clinic.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Trombocitopenia/virologia , Idoso , Humanos , Masculino , Pandemias , Índice de Gravidade de Doença
8.
Medicine (Baltimore) ; 99(36): e22033, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899059

RESUMO

BACKGROUND: In December 2019, the novel coronavirus pneumonia was detected in Wuhan and named COVID-19. It is an international outbreak of the respiratory illness caused by severe acute respiratory syndrome coronavirus 2. Recent papers pointed out the cytopenia in COVID-19 patients including lymphopenia, neutrophilia, thrombocytopenia and lower level of hemoglobin had prognostic significance. This systemic review and meta-analysis summaries the latest evidence from available data and determine the hematological abnormality caused by severe acute respiratory syndrome coronavirus 2 and potential efficacy on the outcomes in patients with COVID-19. METHODS: This protocol for a systematic reviews and meta-analysis will be performed according to the preferred reporting items for systematic reviews and meta-analysis protocols 2015 guidelines. The database of Cochrane Library, PUBMED, EMBASE, Medline, Web of Science, Google Scholar, CNKI, WanFang, as well as gray literatures from the inception to present will be comprehensively and systematically searched without limitations of regions or language. The main study outcomes will be the mortality of COVID-19 patients. The meta-analysis was performed by RevMan V.5.3 program and Stata V.12.0 software after 2 reviewers independently selected literature, data extraction, bias risk evaluation and study quality assessment. Any disagreement will be resolved by consensus to the third researcher. RESULTS: This systematic review and meta-analysis may help provide clarify on the effect of cytopenia in patients with COVID-19. The result will be published at a peer-reviewed journal. CONCLUSIONS: This proposed study will evaluate the existing evidence on the effectiveness of cytopenia in COVID-19 patients. ETHIC AND DISSEMINATION: The content of this article does not involve moral approval or ethical review because no individual data will be collected. PROSPERO REGISTRATION: CRD42020187524.


Assuntos
Infecções por Coronavirus/complicações , Transtornos Leucocíticos/etiologia , Pneumonia Viral/complicações , Trombocitopenia/etiologia , Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Humanos , Transtornos Leucocíticos/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Trombocitopenia/fisiopatologia
9.
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
10.
Lancet ; 396(10254): 839-852, 2020 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-32888407

RESUMO

BACKGROUND: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas. METHODS: We did a seamless design study at 14 cancer centres in the USA. We enrolled adult patients (aged ≥18 years) with relapsed or refractory large B-cell lymphomas. Eligible histological subgroups included diffuse large B-cell lymphoma, high-grade B-cell lymphoma with rearrangements of MYC and either BCL2, BCL6, or both (double-hit or triple-hit lymphoma), diffuse large B-cell lymphoma transformed from any indolent lymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma grade 3B. Patients were assigned to one of three target dose levels of liso-cel as they were sequentially tested in the trial (50 × 106 CAR+ T cells [one or two doses], 100 × 106 CAR+ T cells, and 150 × 106 CAR+ T cells), which were administered as a sequential infusion of two components (CD8+ and CD4+ CAR+ T cells) at equal target doses. Primary endpoints were adverse events, dose-limiting toxicities, and the objective response rate (assessed per Lugano criteria); endpoints were assessed by an independent review committee in the efficacy-evaluable set (comprising all patients who had confirmed PET-positive disease and received at least one dose of liso-cel). This trial is registered with ClinicalTrials.gov, NCT02631044. FINDINGS: Between Jan 11, 2016, and July 5, 2019, 344 patients underwent leukapheresis for manufacture of CAR+ T cells (liso-cel), of whom 269 patients received at least one dose of liso-cel. Patients had received a median of three (range 1-8) previous lines of systemic treatment, with 260 (97%) patients having had at least two lines. 112 (42%) patients were aged 65 years or older, 181 (67%) had chemotherapy-refractory disease, and seven (3%) had secondary CNS involvement. Median follow-up for overall survival for all 344 patients who had leukapheresis was 18·8 months (95% CI 15·0-19·3). Overall safety and activity of liso-cel did not differ by dose level. The recommended target dose was 100 × 106 CAR+ T cells (50 × 106 CD8+ and 50 × 106 CD4+ CAR+ T cells). Of 256 patients included in the efficacy-evaluable set, an objective response was achieved by 186 (73%, 95% CI 66·8-78·0) patients and a complete response by 136 (53%, 46·8-59·4). The most common grade 3 or worse adverse events were neutropenia in 161 (60%) patients, anaemia in 101 (37%), and thrombocytopenia in 72 (27%). Cytokine release syndrome and neurological events occurred in 113 (42%) and 80 (30%) patients, respectively; grade 3 or worse cytokine release syndrome and neurological events occurred in six (2%) and 27 (10%) patients, respectively. Nine (6%) patients had a dose-limiting toxicity, including one patient who died from diffuse alveolar damage following a dose of 50 × 106 CAR+ T cells. INTERPRETATION: Use of liso-cel resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas, including those with diverse histological subtypes and high-risk features. Liso-cel is under further evaluation at first relapse in large B-cell lymphomas and as a treatment for other relapsed or refractory B-cell malignancies. FUNDING: Juno Therapeutics, a Bristol-Myers Squibb Company.


Assuntos
Antígenos CD19/uso terapêutico , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Idoso , Idoso de 80 Anos ou mais , Anemia/epidemiologia , Antígenos CD19/administração & dosagem , Antígenos CD19/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/transplante , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/transplante , Síndrome da Liberação de Citocina/epidemiologia , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Infusões Intravenosas , Leucaférese/métodos , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Doenças do Sistema Nervoso/epidemiologia , Neutropenia/epidemiologia , Recidiva , Segurança , Análise de Sobrevida , Trombocitopenia/epidemiologia , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(39): e21941, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991402

RESUMO

INTRODUCTION: Diffuse pulmonary lymphangiomatosis (DPL) is a rare condition. Most patients with DPL present dyspnea, cough, expectoration, and hemoptysis. There are few reports of DPL accompanied by thrombocytopenia, whose cause remains unknown. PATIENT CONCERNS: An 18-year-old male patient presented with recurrent cough, expectoration, and dyspnea for 5 years, and thrombocytopenia was observed during a 2-month follow-up. DIAGNOSIS: Chest computed tomography showed diffuse patchy shadows in both lungs, and pleural and pericardial effusions. Immunohistochemical lung tissue staining showed lymphatic and vascular endothelial cells positive for D2-40, CD31 and CD34. Routine blood test revealed platelets at 62 × 10 cells/L during follow-up. Bone marrow biopsy was normal. Ultrasound revealed no hepatosplenomegaly. Finally, the patient was diagnosed with DPL accompanied by thrombocytopenia. INTERVENTIONS: He was treated by subtotal pericardial resection, thoracocentesis, and anti-infective therapy. Oral prednisone was administered for 2 months. OUTCOMES: The symptoms of cough and shortness of breath were improved, but thrombocytopenia persisted. We investigated the cause of thrombocytopenia. Whole-exome sequencing identified a mutation in exon 3 of the TNFRSF13B gene in this patient. CONCLUSION: DPL may present with thrombocytopenia and DIC. Patients with thrombocytopenia but not DIC and splenomegaly should be screened for gene mutations.


Assuntos
Pneumopatias/congênito , Linfangiectasia/congênito , Trombocitopenia/complicações , Adolescente , Criança , Humanos , Pneumopatias/complicações , Pneumopatias/diagnóstico por imagem , Pneumopatias/genética , Pneumopatias/patologia , Linfangiectasia/complicações , Linfangiectasia/diagnóstico por imagem , Linfangiectasia/genética , Linfangiectasia/patologia , Masculino , Mutação de Sentido Incorreto , Trombocitopenia/diagnóstico , Tomografia Computadorizada por Raios X , Proteína Transmembrana Ativadora e Interagente do CAML , Sequenciamento Completo do Exoma
12.
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
13.
Epidemiol Infect ; 148: e175, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32782035

RESUMO

Our study aimed to systematically analyse the risk factors of coronavirus disease 2019 (COVID-19) patients with severe disease. An electronic search in eight databases to identify studies describing severe or critically ill COVID-19 patients from 1 January 2020 to 3 April 2020. In the end, we meta-analysed 40 studies involving 5872 COVID-19 patients. The average age was higher in severe COVID-19 patients (weighted mean difference; WMD = 10.69, 95%CI 7.83-13.54). Patients with severe disease showed significantly lower platelet count (WMD = -18.63, 95%CI -30.86 to -6.40) and lymphocyte count (WMD = -0.35, 95%CI -0.41 to -0.30) but higher C-reactive protein (CRP; WMD = 42.7, 95%CI 31.12-54.28), lactate dehydrogenase (LDH; WMD = 137.4, 95%CI 105.5-169.3), white blood cell count(WBC), procalcitonin(PCT), D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine(Cr). Similarly, patients who died showed significantly higher WBC, D-dimer, ALT, AST and Cr but similar platelet count and LDH as patients who survived. These results indicate that older age, low platelet count, lymphopenia, elevated levels of LDH, ALT, AST, PCT, Cr and D-dimer are associated with severity of COVID-19 and thus could be used as early identification or even prediction of disease progression.


Assuntos
Infecções por Coronavirus/epidemiologia , Linfopenia/epidemiologia , Pneumonia Viral/epidemiologia , Trombocitopenia/epidemiologia , Fatores Etários , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Betacoronavirus , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Creatinina/sangue , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Contagem de Linfócitos , Linfopenia/sangue , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Pró-Calcitonina/sangue , Fatores de Risco , Índice de Gravidade de Doença , Trombocitopenia/sangue
14.
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
16.
BMC Infect Dis ; 20(1): 575, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758175

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with the high case-fatality rate, and lack of vaccines. We aimed to systematically analysed the epidemiological characteristics, clinical signs, routine laboratory diagnosis, risk factors, and outcomes. METHODS: Documents on SFTS were collected by searching the Chinese National Knowledge Infrastructure, Wan Fang Data, PubMed, Embase, and Web of Science databases from 2011 to 2018. Meta-analysis was performed by using Review Manager and Stata software. RESULTS: Twenty-five articles involving 4143 cases were included. Diarrhea (odds ratio (OR) =1.60, 95% confidence interval (CI): 1.06 to 2.42, P = 0.02), and vomiting (OR = 1.56, 95% CI: 1.01 to 2.39, P = 0.04) on admission were associated with the fatal outcomes of SFTS. Compared to patients with mild symptoms, patients with severe symptoms had significantly elevated levels of lactic acid dehydrogenase (standard mean difference (SMD) =1.27, 95% CI: 0.59 to 1.94), alanine aminotransferase (SMD = 0.55, 95% CI: 0.24 to 0.85), aspirate aminotransferase (SMD = 1.01, 95% CI: 0.69 to 1.32), and creatine kinase (SMD = 1.04, 95% CI: 0.74 to 1.33) but had reduced platelet counts (SMD = -0.87, 95% CI: - 1.16 to - 0.58) and albumin levels (SMD = -1.00, 95% CI: - 1.32 to - 0.68). The risk factors for poor prognosis included age (mean difference (MD) =6.88, 95% CI: 5.41 to 8.35) and farming (OR = 2.01, 95% CI: 1.06 to 3.80). For the risk factors of contracting SFTS, the incidence of SFTS related to tick bites was 24% [95% CI: 0.18 to 0.31]. The pooled case-fatality rate of SFTS patients was 18% [95% CI: 0.16 to 0.21]. CONCLUSIONS: China is the country with the highest incidence of SFTS. May to July was the peak of the epidemic, and farmers were a high-risk group. The risk factor for SFTS included age (poor prognosis) and tick bites (contracting SFTS). Patients with severe diarrhea and vomiting symptoms on admission should be noted. Clinicians could use routine laboratory parameters and clinical symptoms as references for clinically suspected cases, classification of SFTS, and timely treatment, especially in basic hospitals.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Epidemias , Febre por Flebótomos/complicações , Febre por Flebótomos/epidemiologia , Phlebovirus/imunologia , Trombocitopenia/complicações , Trombocitopenia/epidemiologia , Idoso , Anticorpos Antivirais/sangue , China/epidemiologia , Doenças Transmissíveis Emergentes/sangue , Doenças Transmissíveis Emergentes/virologia , Fazendeiros , Feminino , Febre/complicações , Humanos , Incidência , Leucopenia/complicações , Masculino , Pessoa de Meia-Idade , Febre por Flebótomos/sangue , Febre por Flebótomos/virologia , Phlebovirus/isolamento & purificação , RNA Viral/sangue , Fatores de Risco , Síndrome , Trombocitopenia/virologia
17.
BMC Infect Dis ; 20(1): 595, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787952

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a severe systemic virus infectious disease usually having multi-organ dysfunction which resembles sepsis. METHODS: Data of 321 patients with laboratory-confirmed SFTS from May 2013 to July 2017 were retrospectively analyzed. Demographic and clinical characteristics, calculated quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for survivors and nonsurvivors were compared. Independent risk factors associated with in-hospital mortality were obtained using multivariable logistic regression analysis. Risk score models containing different risk factors for mortality in stratified patients were established whose predictive values were evaluated using the area under ROC curve (AUC). RESULTS: Of 321 patients, 87 died (27.1%). Age (p < 0.001) and percentage numbers of patients with qSOFA≥2 and SIRS≥2 (p < 0.0001) were profoundly greater in nonsurvivors than in survivors. Age, qSOFA score, SIRS score and aspartate aminotransferase (AST) were independent risk factors for mortality for all patients. qSOFA score was the only common risk factor in all patients, those age ≥ 60 years and those enrolled in the intensive care unit (ICU). A risk score model containing all these risk factors (Model1) has high predictive value for in-hospital mortality in these three groups with AUCs (95% CI): 0.919 (0.883-0.946), 0.929 (0.862-0.944) and 0.815 (0.710-0.894), respectively. A model only including age and qSOFA also has high predictive value for mortality in these groups with AUCs (95% CI): 0.872 (0.830-0.906), 0.885(0.801-0.900) and 0.865 (0.767-0.932), respectively. CONCLUSIONS: Risk models containing qSOFA have high predictive validity for SFTS mortality.


Assuntos
Escores de Disfunção Orgânica , Febre por Flebótomos/complicações , Febre por Flebótomos/mortalidade , Phlebovirus/genética , Trombocitopenia/complicações , Trombocitopenia/mortalidade , Fatores Etários , Idoso , Área Sob a Curva , Aspartato Aminotransferases/sangue , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Febre por Flebótomos/sangue , Prognóstico , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Sepse/mortalidade , Síndrome
18.
Diabetes Metab J ; 44(4): 602-613, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32794386

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. METHODS: We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. RESULTS: Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. CONCLUSION: DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.


Assuntos
Infecções por Coronavirus/mortalidade , Diabetes Mellitus/epidemiologia , Pneumonia Viral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/metabolismo , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aspartato Aminotransferases/metabolismo , Betacoronavirus , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Comorbidade , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Linfocitose , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Quarentena/estatística & dados numéricos , República da Coreia/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Trombocitopenia
19.
Lancet Haematol ; 7(9): e640-e648, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32853584

RESUMO

BACKGROUND: Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin. METHODS: We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 109 cells per L before major surgery or less than 50 × 109 cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 109 cells per L before major surgery or 45 × 109 cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov, NCT01621204. FINDINGS: Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49-55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; pnon-inferiority=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI -2·1%; pnon-inferiority=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred. INTERPRETATION: Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles. FUNDING: GlaxoSmithKline and Novartis.


Assuntos
Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Pirazóis/uso terapêutico , Trombocitopenia/tratamento farmacológico , Administração Oral , Adulto , Idoso , Fibrilação Atrial/etiologia , Benzoatos/efeitos adversos , Feminino , Humanos , Hidrazinas/efeitos adversos , Imunoglobulinas Intravenosas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pancreatite/etiologia , Assistência Perioperatória , Contagem de Plaquetas , Embolia Pulmonar/etiologia , Pirazóis/efeitos adversos , Resultado do Tratamento , Vertigem/etiologia
20.
Lancet Haematol ; 7(9): e649-e659, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32758434

RESUMO

BACKGROUND: Avadomide (CC-122) is a novel oral cereblon-modulating agent with promising activity in non-Hodgkin lymphoma. We aimed to examine the safety and preliminary activity of avadomide plus obinutuzumab in patients with relapsed or refractory non-Hodgkin lymphoma. METHODS: CC-122-NHL-001 was a phase 1b dose escalation and expansion study at eight sites in France, Italy, and the Netherlands. Eligible patients (aged ≥18 years) had histologically confirmed CD20-positive relapsed or refractory non-Hodgkin lymphoma, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had received previous treatment. In the dose expansion phase, only patients with previously treated relapsed or refractory follicular lymphoma (grade 1, 2, or 3a) were included. Avadomide was administered in escalating doses and two formulations: active pharmaceutical ingredient in capsule in 1·0 mg, 2·0 mg, 3·0 mg, and 4·0 mg doses and as formulated capsules in 3·0 mg and 4·0 mg doses orally once daily on days 1-5 followed by 2 days off (5-7-day schedule) every week of each 28-day cycle. Obinutuzumab 1000 mg was administered intravenously on days 2, 8, and 15 of cycle 1 and day 1 of cycles 2-8. Primary objectives were to determine the safety and tolerability, the non-tolerated dose, maximum tolerated dose, and recommended phase 2 dose (RP2D). All patients who received treatment were included in the safety analyses. Efficacy-evaluable patients completed at least one cycle of treatment and had baseline and at least one post-baseline assessment. The study is registered with ClinicalTrials.gov, NCT02417285 and EudraCT 2014-003333-26, and is ongoing. FINDINGS: Between June 24, 2015, and Dec 5, 2018, 73 patients were enrolled and treated; 19 had diffuse large B-cell lymphoma, 53 follicular lymphoma, and one marginal zone lymphoma. Median follow-up was 253 days (IQR 127-448). The median number of previous anticancer regimens was three (IQR 2-4). The maximum tolerated dose and non-tolerated dose were not reached in the dose escalation phase. On the basis of safety and pharmacokinetic-pharmacodynamic data, the avadomide RP2D was established as 3·0 mg as formulated capsules on a 5-7-day schedule in combination with 1000 mg of obinutuzumab. Patients enrolled in the expansion cohort received the established RP2D of avadomide. Across all doses, three patients had dose-limiting toxicities; one patient treated at the RP2D had dose-limiting toxicity (grade 3 sepsis). The most common adverse events of grade 3 and above were neutropenia (41 [56%] of 73) and thrombocytopenia (17 [23%] of 73). 34 (47%) patients had serious adverse events, which were considered to be avadomide-related in 23 (32%) of 73 patients and obinutuzumab-related in 20 (27%) of 73 patients. Two treatment-related deaths occurred, one owing to tumour flare and one from acute myeloid leukaemia after study discontinuation. INTERPRETATION: Avadomide plus obinutuzumab has a manageable toxicity, being a tolerable treatment option for most patients. Although the prespecified threshold for activity was not met in the trial, we believe that the preliminary antitumour activity of cereblon modulators plus next-generation anti-CD20 antibodies in heavily pretreated relapsed or refractory non-Hodgkin lymphoma warrants further investigation as a chemotherapy-free option in this setting. FUNDING: Celgene Corporation.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidonas/uso terapêutico , Quinazolinonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/patologia , Piperidonas/efeitos adversos , Piperidonas/farmacocinética , Quinazolinonas/efeitos adversos , Quinazolinonas/farmacocinética , Recidiva , Índice de Gravidade de Doença , Trombocitopenia/etiologia , Trombocitopenia/patologia , Resultado do Tratamento
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