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Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are widely recognised as being able to induce a potent reduction in lowdensity lipoproteincholesterol. An increasing number of studies have suggested that PCSK9 also influences the haemostatic system by altering platelet function and the coagulation cascade. These findings have significant implications for antiPCSK9 therapy in patients with specific coagulation conditions, including expanded indications, dose adjustments and drug interactions. The present review summarises the changes in PCSK9 levels in individuals with liver diseases, chronic kidney diseases, diabetes mellitus, cancer and other disease states, and discusses their impact on thrombosis and haemostasis. Furthermore, the structure, effects and regulatory mechanisms of PCSK9 on platelets, coagulation factors, inflammatory cells and endothelial cells during coagulation and haemostasis are described.
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Hemostasia , Pró-Proteína Convertase 9 , Trombose , Humanos , Pró-Proteína Convertase 9/metabolismo , Hemostasia/efeitos dos fármacos , Trombose/metabolismo , Trombose/tratamento farmacológico , Animais , Plaquetas/metabolismo , Inibidores de PCSK9 , Metabolismo dos Lipídeos/efeitos dos fármacosRESUMO
In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .
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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/tratamento farmacológico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Aminopiridinas/uso terapêutico , Benzamidas/uso terapêutico , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologia , Transplante Autólogo , Idoso , Taxa de Sobrevida , Adulto Jovem , Quimioterapia de Manutenção , Autoenxertos , Indução de Remissão , AdolescenteRESUMO
Unfit acute myeloid leukemia and high-risk myelodysplastic syndrome patients with prolonged neutropenia demand coadministration of venetoclax and azoles. However, venetoclax dosing under drug-drug interaction with azoles remains controversial. Therapeutic drug monitoring (TDM) is expected to guide drug dosage adjustments. We retrospectively enrolled 17 patients under this coadministration and TDM. Venetoclax dosages were interfered when inappropriate drug concentrations appeared. The primary endpoints were objective response and adverse events. Venetoclax concentration outliers were more frequently evaluated before than after dose adjustment (Cmax 60.87% vs. 0.00%, p < .0001). MRD negativity rate was higher in patients staying within reference range than those having outliers (90.91% vs. 33.33%, p = .028). Objective response rate was 100%. Hematologic adverse events included neutropenia (93.3%), febrile neutropenia (53.3%), and thrombocytopenia (81.3%). Median time to neutropenia and thrombocytopenia recovery was 20 (14-32) and 16.5 (6-34) days, respectively. No invasive fungal and other life-threatening infections were observed.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Neutropenia , Sulfonamidas , Trombocitopenia , Humanos , Antifúngicos/efeitos adversos , Estudos Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/induzido quimicamente , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/tratamento farmacológico , Azóis/uso terapêutico , Trombocitopenia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).
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Hiperplasia do Linfonodo Gigante , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/epidemiologia , Hiperplasia do Linfonodo Gigante/terapia , Estudos Retrospectivos , Pequim/epidemiologia , Prognóstico , China/epidemiologiaRESUMO
BACKGROUND: This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs). METHODS: The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort. RESULTS: A total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7-51.2] in the MTX cohort and 24.3 months (95% CI: 16.6-32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8-35.2) in the MTX cohort and 32 months (95% CI: 27.6-36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts. CONCLUSIONS: This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate - based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.
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Neoplasias do Sistema Nervoso Central , Linfoma , Adulto , Humanos , Metotrexato/uso terapêutico , Teniposídeo/uso terapêutico , Quimioterapia de Indução , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/patologia , Sistema Nervoso CentralRESUMO
Renal impairment (RI) is a very common complication of multiple myeloma (MM) with a negative impact on survival. Herein we retrospectively analyzed 334 MM patients with renal impairment at diagnosis from three hospitals in China. All 334 patients were divided into three groups, including dialysis dependence (n=43), dialysis independence (n=42), and without dialysis (n=249). Compared with dialysis independence and without dialysis groups, dialysis dependence group had the lowest overall hematologic response (48.8% vs. 97.6% vs. 77.1%, P<0.001) and overall renal response (0.0% vs. 97.6% vs. 72.7%, P<0.001), as well as the highest early mortality within 24 months (50.0% vs. 24.4% vs. 26.3%, P=0.006). Dialysis dependence group had similar progression-free survival (24 vs. 26 vs. 27 months, P=0.231) and significantly shorter overall survival (25 vs. 69 vs. 45 months, P=0.001). Dialysis dependence was independently associated with high mortality within 24 months and shorter overall survival. In conclusion, MM patients with dialysis dependence still tend to suffer a dismal disease course, including a high probability to suffer early mortality, worse hematological and renal response, as well as shorter survival. Dialysis independence could be very promising for survival improvement.
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Light chain amyloidosis is a plasma cell dyscrasia characterized by deposition of misfolded amyloid fibrils in tissues, leading to multi-organ dysfunction. We retrospectively analyzed 335 patients (median age, 60 years) with systemic light chain amyloidosis in the First Hospital of Peking University from 2011 to 2021. Involved organs were the kidney (92.8%), heart (57.9%), liver (12.8%) and peripheral nervous system (6.3%). Chemotherapy was administered to 55.8% (187/335) of patients, among whom 94.7% received novel agent-based regimens. Hematologic response (≥ very good partial response) was achieved in 63.4% of patients who received chemotherapy. Only 18.2% of patients received autologous hematopoietic stem cell transplant (ASCT). Among transplant-eligible patients, the overall survival of ASCT recipients was better than those who received chemotherapy only. The median overall survival of the patients with light chain amyloidosis was 77.5 months. Estimated glomerular filtration rate and Mayo 2012 stage were independent prognostic factors for overall survival in multivariate analysis. Although the younger age and high ratio of renal involvement might contribute to the favorable prognosis of this cohort, the role of novel agents and ASCT is also discernible. This study will provide a comprehensive perspective on progress in treatment of light chain amyloidosis in China.
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Amiloidose , Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , População do Leste Asiático , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Prognóstico , Transplante AutólogoRESUMO
BACKGROUND: In the phase 3 LEPUS study, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Here, we report updated efficacy and safety results from LEPUS. PATIENTS AND METHODS: Chinese patients with ≥ 1 prior line of therapy were randomized 2:1 to bortezomib (1.3 mg/m2) and dexamethasone (20 mg) for eight cycles ± daratumumab (16 mg/kg) until disease progression. The primary endpoint was progression-free survival (PFS). RESULTS: In total, 211 patients were randomized to D-Vd (n = 141) or Vd (n = 70). At a 25.1-month median follow-up, D-Vd prolonged PFS versus Vd (median, 14.8 vs. 6.3 months; hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.24-0.51; P < .00001). PFS benefit of D-Vd versus Vd was maintained across prespecified subgroups, including patients with prior bortezomib (HR, 0.36; 95% CI, 0.25-0.53), patients who were refractory to last prior line of therapy (HR, 0.42; 95% CI, 0.27-0.65), and patients with high-risk cytogenetics (HR, 0.41; 95% CI, 0.23-0.71). Overall response rate (84.7% vs.66.7%; P = .00314) and rates of very good partial response or better (71.5% vs. 34.9%; P < .00001) and complete response or better (40.1% vs 14.3%; P = .00016) were higher with D-Vd versus Vd. No new safety concerns were identified. CONCLUSIONS: In this updated analysis, D-Vd maintained significant efficacy benefits versus Vd alone and demonstrated a consistent safety profile, further supporting the use of D-Vd as a standard of care in Chinese patients with RRMM.
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Mieloma Múltiplo , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , População do Leste Asiático , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
Objectives: Myelomatous pleural effusion is a rare presentation of extramedullary disease in multiple myeloma, which has been reported with dismal prognosis. We aimed to explore whether it has distinctive clinical characteristics and outcomes compared to other anatomic locations of extramedullary involvements. Methods: Multiple myeloma patients diagnosed at our institution from 2010 to 2020 were retrieved retrospectively. In total, 42 pairs of patients with and without extramedullary disease were enrolled, including 13 with myelomatous pleural effusion. The clinical and laboratory parameters were collected and compared between different groups. Prognostic effect of myelomatous pleural effusion was assessed in cox regression model and Kaplan-Meier curves. Results: Myelomatous pleural effusion patients presented a higher level of ß2-microglobulin (P = .041), greater prevalence of multisites extramedullary lesions (69.2% vs 38.0%, P = .036) and International Staging System stage III (76.9% vs 44.8%, P = .016). Median overall survival was 60.6 months in patients without extramedullary disease versus 35.0 months in patients with extramedullary disease (P = .045). Notably, median overall survival was 13.0 months in myelomatous pleural effusion patients versus 37.0 months in other extramedullary disease patients with a significant difference (P = .029). Furtherly, multivariate analysis recognized myelomatous pleural effusion as an independent prognostic indicator (Hazard ratio: 2.669, 95% CI [1.132-6.293], P = .025). Conclusion: Myelomatous pleural effusion patients presented heavier tumor burden and worse outcomes than other extramedullary diseases.
Assuntos
Mieloma Múltiplo , Derrame Pleural Maligno , Derrame Pleural , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/etiologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: 5-Hydroxymethylcytosine (5hmC), an important DNA epigenetic modification, plays a vital role in tumorigenesis, progression and prognosis in many cancers. Diffuse large B cell lymphoma (DLBCL) can involve almost any organ, but the prognosis of patients with DLBCL at different primary sites varies greatly. Previous studies have shown that 5hmC displays a tissue-specific atlas, but its role in DLBCLs at different primary sites remains unknown. RESULTS: We found that primary gastric DLBCL (PG-DLBCL) and lymph node-involved DLBCL (LN-DLBCL) patients had a favorable prognosis, while primary central nervous system DLBCL (PCNS-DLBCL) patients faced the worst prognosis, followed by primary testicular DLBCL (PT-DLBCL) and primary intestinal DLBCL (PI-DLBCL) patients. Thus, we used hmC-CATCH, a bisulfite-free and cost-effective 5hmC detection technology, to first generate the 5hmC profiles from plasma cell-free DNA (cfDNA) of DLBCL patients at these five different primary sites. Specifically, we found robust cancer-associated features that could be used to distinguish healthy individuals from DLBCL patients and distinguish among different primary sites. Through functional enrichment analysis of the differentially 5hmC-enriched genes, almost all DLBCL patients were enriched in tumor-related pathways, and DLBCL patients at different primary sites had unique characteristics. Moreover, 5hmC-based biomarkers can also highly reflect clinical features. CONCLUSIONS: Collectively, we revealed the primary site differential 5hmC regions of DLBCL at different primary sites. This new strategy may help develop minimally invasive and effective methods to diagnose and determine the primary sites of DLBCL.
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Ácidos Nucleicos Livres , Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Adulto , Biomarcadores/metabolismo , Neoplasias do Sistema Nervoso Central/diagnóstico , Metilação de DNA , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , PrognósticoRESUMO
Background: Patients with amyloid light-chain (AL) amyloidosis with a bone marrow plasma cell ratio > 10% (AL-PCMM) have a poorer prognosis than patients with AL amyloidosis with a bone marrow plasma cell ratio of <10% (AL-only), similar to that of patients with AL amyloidosis and multiple myeloma (AL-MM). However, the prognostic factors for AL-PCMM and AL-MM have not been studied. Methods: A total of 49 patients with AL-PCMM or AL-MM in the Peking University First Hospital registry in 2010-2018 were enrolled. Clinical and follow-up data were collected. The relationship between clinical parameters and survival time was also assessed. Results: Compared with patients with AL-PCMM, patients with AL-MM only had a higher incidence of bone marrow plasma cell ratio ≥ 20%. In AL-PCMM and AL-MM, the survival time was significantly shorter in patients with alkaline phosphatase (ALP) ≥ 187.5 IU/L, γ-glutamyl transpeptidase (GGT) ≥ 85 IU/L, total bilirubin (TBIL) ≥ 20 µmol/L, cardiac troponin I (CTNI) ≥ 0.1 ng/mL, ejection fraction (EF) < 50%, initial therapeutic effect (ITE) < very good partial response (VGPR), and Boston University (BU) staging system stage ≥ III. ALP at diagnosis was correlated with brain natriuretic peptide (BNP) level, CTNI level, and EF rather than TBIL level. Cox regression analyses revealed that BU staging system stage ≥ III (P=0.001, hazard ratio [HR]=5.579), ALP ≥ 187.5 IU/L (P=0.011, HR=3.563), and ITE < VGPR (P=0.002, HR=7.462) were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM. Conclusion: ALP level, which is related to cardiac amyloidosis rather than liver involvement, can be a prognostic factor for this group of patients. A BU staging system stage ≥ III, ALP ≥ 187.5 IU/L, and ITE < VGPR were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM.
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Amiloidose de Cadeia Leve de Imunoglobulina , Mieloma Múltiplo , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Prognóstico , Estudos Retrospectivos , Troponina IRESUMO
Background: 5-Hydroxymethylcytosine (5-hmC), a stable epigenetic marker, is closely related to tumor staging, recurrence and survival, but the prognostic value of 5-hmC in primary testicular diffuse large B-cell lymphoma (PT-DLBCL) remains unclear. This study aimed to investigate the 5-hmC expression in PT-DLBCL and evaluate its prognostic value. Methods: A total of 34 patients with PT-DLBCL treated in the Department of Hematology from August 2000 to August 2020 were included in this study. The expression of 5-hmC in PT-DLBCL tissues and normal testicular tissues were assessed by immunohistochemistry. 5-hmC staining is estimated as a percentage under every nuclear staining intensity score (0-3), 0 or 1 of which were regarded as 5-hmC reduction. The quantification of 5-hmC reduction is defined as the percentage of cells with 5-hmC staining scores of 0 and 1. According 5-hmC reduction of 80%, a 5-hmC reduction of <80% is regarded as "5-hmC high-level group", and a 5-hmC reduction of ≥80% is regarded as "5-hmC low-level group". Furthermore, Cox regression model was used to evaluate the prognostic value of all covariates. Results: The median percentage of 5-hmC reduction in the PT-DLBCL group was 77.50% (60%-90%), the median 5-hmC reduction in the normal testicular tissues was 30% (20%-50%). Compared with normal testicular tissue, 5-hmC levels in PT-DLBCL tissue were significantly decreased (p<0.05). Of the 34 PT-DLBCL patients, 17 had tumors with relatively low 5-hmC expression (5-hmC reduction of ≥80%) and 17 had tumors with relatively high 5-hmC expression (5-hmC reduction of < 80%). 5-hmC expression was negatively correlated with international prognostic index (p = 0.037), while there was no significant difference in 5-hmC decrease among different groups of age at diagnosis, lactate dehydrogenase, testicular lymphoma involvement (unilateral or bilateral), Ki-67 and tumor diameter. Relatively low 5-hmC expression indicated shorter overall survival (OS) (5-year OS 50.2% vs 81.3%, p=0.022) and progression-free survival (PFS) (5-year PFS 38.5% vs 70.7%, p=0.001). Cox multivariate analysis of IPI (2-3 vs. 0-1), intrathecal prophylaxis (No vs. Yes), and 5-hmC reduction (≥80% vs. <80%) showed that 5-hmC reduction ≥80% (hazard ratio: 7.252, p = 0.005) and not receiving intrathecal prophylaxis (hazard ratio: 7.207, p =0.001) are independent risk factors for poor prognosis of PT-DLBCL. Conclusion: Our results suggested that 5-hmC decline can be identified as a poor prognostic predictor for PT-DLBCL. It is necessary to further explore the underlying mechanism of this epigenetic marker to identify methods to re-establish 5-hmC levels and provide new targets for cancer therapy.
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5-Metilcitosina/análogos & derivados , Linfoma Difuso de Grandes Células B/diagnóstico , Estadiamento de Neoplasias/métodos , Neoplasias Testiculares/diagnóstico , 5-Metilcitosina/análise , Idoso , Biomarcadores Tumorais/genética , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Testiculares/genética , Testículo/metabolismoRESUMO
BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.
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Fragilidade , Mieloma Múltiplo , Idoso , Idoso de 80 Anos ou mais , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Mieloma Múltiplo/diagnóstico , Estudos ProspectivosRESUMO
OBJECTIVE: T cell lymphomas are associated with an aggressive worse prognosis. This study is designed to assess T cell lymphomas using 18F-FDG PET/CT. METHODS: Sixty-four patients with newly diagnosed T cell lymphomas underwent PET/computed tomography (PET/CT) scans, 47 cases who were fully followed up were retrospectively reviewed and analyzed. Overall survival (OS) and progression-free survival (PFS) were recorded for prognosis. We measured the maximum standardized uptake value (SUVmax) in all cases, analyzed the correlation between SUVmax and survival and other clinicopathologic parameters. Kaplan-Meier log-rank tests were then used to compare the survival of high and low PET/CT parameter groups, and multivariate Cox proportional hazards regression analysis was carried out to identify predictors of OS and PFS. RESULTS: With a median follow-up of 26.5 (range 0.7-117.5) months, the 1-, 2- and 3-year OS were 75.6, 61.7 and 49.2%, and PFS were 49.3, 39.9 and 29.9%, respectively in 47 patients. Among them, 33 cases progressed with a median time of 9.5 (0.7-115.0) months, and 26 patients died with a median survival time of 26.5 (0.7-117.5) months. Multivariate analysis showed the following independent prognostic factors for OS: age >60 years (P = 0.002), SUVmax >9.7 (P = 0.009) and extranodal involvement of more than one site (P = 0.018). In addition, lactate dehydrogenase level (P = 0.003) and B symptoms (P = 0.018) were independent risk factors for PFS. CONCLUSION: Pretherapy SUVmax may serve as an independent predictor of outcome in patients with newly diagnosed T cell lymphomas.
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Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
BACKGROUND: Myelomatous pleural effusion (MPE), as a presentation of extramedullary infiltration of multiple myeloma (MM), is rare and currently associated with poor outcomes without effective therapy. The potential value of cytokine detection in pleural effusion to MPE has not been reported to date. CASE PRESENTATION: We herein report a case of refractory and relapsed multiple myeloma that developed bilateral MPE due to disease progression caused by intolerance to various chemotherapy regimens. Cytomorphology and flow cytometry were adopted for diagnosis confirmation. Chemotherapy containing immunomodulators combined with thoracic catheterization drainage was applied to the patient, showing a certain therapeutic effect. During the course of disease, the change of cytokine profile in pleural effusion was monitored by cytometric bead array (CBA) technology, revealing that cytokines related to tumor load such as interleukin 6 (IL-6) and interleukin 10 (IL-10) in pleural effusion decreased with the improvement of disease, while other cytokines such as interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 17A (IL-17A), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), granzyme A, granzyme B, perforin and granulysin increased with the improvement of disease. CONCLUSION: There is a prospect that cytokine level in pleural effusion may indicate treatment response of MPE, and in light of this case, immunomodulators may be utilized in treating patients suffering MPE. Due to limitations of our single case, we urge more groups to evaluate the potential role of cytokine profile in MPE.
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BACKGROUND: Daratumumab plus bortezomib/dexamethasone (D-Vd) significantly improved outcomes versus Vd in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 CASTOR study. We report the results of a prespecified interim analysis of the phase 3 LEPUS study of D-Vd versus Vd in Chinese patients with RRMM. PATIENTS AND METHODS: Chinese patients with ≥ 1 prior line of therapy were randomized 2:1 to receive 8 cycles (21 days/cycle) of bortezomib (1.3 mg/m2 subcutaneously) and dexamethasone (20 mg orally/intravenously) ± daratumumab (16 mg/kg intravenously). The primary endpoint was progression-free survival (PFS). RESULTS: A total of 211 patients were randomized (D-Vd, 141; Vd, 70). After an 8.2-month median follow-up, D-Vd significantly prolonged PFS versus Vd (median, not reached vs. 6.3 months; hazard ratio, 0.28; 95% confidence interval, 0.17-0.47; P < .00001) and significantly improved the rates of overall response (83% vs. 65%; Pâ¯=â¯.00527), ≥ very good partial response (65% vs. 33%; Pâ¯=â¯.00002), ≥ complete response (33% vs. 11%; Pâ¯=â¯.00079), and minimal residual disease negativity (10-5 sensitivity; 22% vs. 3%; Pâ¯=â¯.0002). The PFS benefit of D-Vd versus Vd was maintained across prespecified subgroups, including patients with prior bortezomib treatment and with high-risk cytogenetics. Thrombocytopenia (D-Vd, 51%; Vd, 37%), lymphopenia (44%; 29%), and lung infection (30%; 22%) were the 3 most common grade 3/4 treatment-emergent adverse events. Although patients in both treatment groups experienced higher rates of grade 3/4 lymphopenia and infections versus patients in CASTOR, the safety profile was generally consistent with that of CASTOR. CONCLUSION: These data support the use of D-Vd in Chinese patients with RRMM.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Bortezomib/farmacologia , China , Dexametasona/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: Monoclonal immunoglobulin-associated renal lesions in patients with newly diagnosed myeloma vary. We aimed to determine the pathological spectrum and analyze associated prognostic factors. METHODS: Fifty-six patients with newly diagnosed multiple myeloma and biopsy-proven renal lesions were enrolled. Kidney biopsies were reanalyzed, and the baseline clinical characteristics, treatments and outcomes were recorded. RESULTS: Fifty-one patients had monoclonal immunoglobulin-associated renal lesions, with myeloma cast nephropathy (MCN) being the most common pattern. We divided our cohort into pure MCN, MCN+ other pathologies and non-MCN. Patients with MCN had more severe renal injury than those with non-MCN. In our cohort, none of the patients with pure MCN or MCN + other pathologies presented with nephrotic syndrome. Patients with non-MCN had better renal and overall survival than those with pure MCN but similar survivals to those with MCN + other pathologies. Number of myeloma casts (HR 1.08, p = 0.012) was the only independent prognostic factor for renal survival. Male sex (HR: 3.64; p = 0.015) and number of casts (HR: 1.17; p = 0.001) were independent prognostic factors for overall survival. CONCLUSION: Patients with MCN had more severe renal injury than those with non-MCN. Patients with non-MCN had better renal and overall outcomes than those with pure MCN, but their outcomes were similar to those with MCN + other pathologies. The independent predictors of overall survival were male sex and number of myeloma casts.
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OBJECTIVE: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL). METHODS: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS). RESULTS: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable. CONCLUSIONS: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
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BACKGROUND: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis are not particularly clear. METHODS: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information was collected from first presentation to death or until the last available clinical follow-up. The patients' survival and outcomes were analyzed, and the relationship between the clinical parameters and survival was also assessed. RESULTS: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNPâ§700pg/mL (P<0.001), ALP>187.5IU/L (P=0.032) and ALB<25g/L (P<0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNPâ§700pg/mL (P=0.030) and Alb<25g/L (P=0.024). The existence of AL amyloidosis, especially those with the heart involvement, was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on the symptomatic multiple myeloma. Cox regression model for overall survival detected BNPâ§700pg/mL in symptomatic multiple myeloma having independent poorer prognostic significance (HR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P<0.001). Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent poorer prognostic significance (HR=8.741, P=0.002). CONCLUSION: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma. It is mainly because of involvement of important organs, especially the heart. AL amyloidosis probably has a greater impact on the prognosis of smoldering multiple myeloma than on the symptomatic multiple myeloma.
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BACKGROUND: This study assessed the clinical characteristics of gastrointestinal bleeding (GIB), obstruction (GIO), and perforation (GIP) in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and the influence on long-term survival. METHODS: A retrospective analysis was performed of 148 patients with PGI-DLBCL admitted to Peking University First Hospital from August 1994 to May 2018. The clinical characteristics of GIB, GIO, and GIP before and after chemotherapy were recorded. The associated overall survival and progression-free survival were analyzed. RESULTS: Among 148 patients, 56.8% had gastrointestinal complications (GICs), including GIB, GIO, GIP, and multiple complications, and 22.6% of them occurred after chemotherapy, mostly during the first 4 cycles. The most common clinical manifestations of patients with GICs were abdominal pain or discomfort (79.8%), hematemesis or melena (22.6%), and abnormal bowel habits (17.9%). Patients with Eastern Cooperative Oncology Group (ECOG) score ≥2, tumor mass ≥10 cm, or intestinal involvement had significantly higher risk of severe GICs as initial manifestations. Among 130 patients who received chemotherapy, B symptoms, tumor mass ≥10 cm, and Lugano stage (IIE, IV) strongly correlated with GICs after chemotherapy (P < 0.05). Rituximab did not increase the risk of GICs. GICs which occurred before or after chemotherapy reduced the objective response rate at the end of chemotherapy. The prognosis of patients was significantly worsened by GIP, GIB, or multiple complications after chemotherapy (P < 0.05). GIB at presentation or GIO before or after chemotherapy had no prognostic value (both P > 0.05). CONCLUSION: GICs adversely affect the quality of life, prolong the length of hospitalization, and shorten the long-term survival of patients with PGI-DLBCL.