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1.
Medicine (Baltimore) ; 100(46): e27898, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797341

RESUMO

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a critical thrombotic microangiopathy involving multiple organs. To the best of our knowledge, there are no reports of TTP complicated by acute aortic dissection. PATIENT CONCERNS: We herein described a 53-year-old male with TTP who did not have a significant medical history. After immediate plasma exchange and glucocorticoid therapy, the patient's clinical condition improved. However, the patient suddenly experienced chest pain with elevated blood pressure. DIAGNOSES: Computed tomography angiography suggested acute type B aortic dissection. INTERVENTIONS: The patient was immediately transferred to the cardiac aortic surgery department for thoracic aortic endovascular repair. OUTCOMES: The patient was discharged after successful thoracic aortic endovascular repair. Unfortunately, 3 months later, the patient experienced chest and back pain at home and died suddenly, possibly due to the recurrence of aortic dissection. LESSONS: Even if patients have no identifiable risk factors, physicians should be aware of this rare and life-threatening acute complication of TTP, which may have multiple causes, including preexisting connective tissue disease, abnormal blood pressure fluctuations, and increased risk of hemorrhage. Early identification and timely treatment of acute aortic dissection are critical for improving prognosis.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1601-1605, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627447

RESUMO

OBJECTIVE: To analyze the clinical efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH), and preliminarily explore the role of an improved post-transplantation cyclophosphamide (PTCy) based conditioning regimen in PNH patients receiving transplantation. METHODS: Clinical related data of PNH sufferers receiving allo-HSCT in Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected, and hematopoietic reconstitution, chimerism, PNH cloning, graft-versus-host disease (GVHD), infection, and survival were analyzed. RESULTS: Totally five PNH patients receiving allo-HSCT were enrolled, including 1 case with classic PNH, 3 cases with aplastic anemia-PNH syndrome, 1 case with myelodysplastic syndrome, three of them (case 1-3) received the improved PTCy based conditioning regimen before HSCT. All sufferers engrafted successfully within 28 days, the median time of neutrophil and platelet engraftment was 11 days and 12 days, respectively, no patient occurred acute or chronic GVHD, after a median follow-up of 16 months, all recipients survived and completely eliminated PNH cloning. CONCLUSION: Allo-HSCT can completely clear PNH cloning and restore hematopoietic function with controllable complications, and the improved PTCy based conditioning regimen is proved to be effective in PNH transplantation.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística , Anemia Aplástica/terapia , Hemoglobinúria Paroxística/terapia , Humanos , Condicionamento Pré-Transplante
4.
Biomed Res Int ; 2021: 8569921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34327238

RESUMO

Doxorubicin is a cornerstone chemotherapeutic drug widely used to treat various cancers; its dose-dependent cardiomyopathy, however, is one of the leading causes of treatment-associated mortality in cancer survivors. Patients' threshold doses leading to doxorubicin-induced cardiomyopathy (DIC) and heart failure are highly variable, mostly due to genetic variations in individuals' genomes. However, genetic susceptibility to DIC remains largely unidentified. Here, we combined a genetic approach in the zebrafish (Danio rerio) animal model with a genome-wide association study (GWAS) in humans to identify genetic susceptibility to DIC and heart failure. We firstly reported the cardiac and skeletal muscle-specific expression and sarcomeric localization of the microtubule-associated protein 7 domain-containing protein 1b (Map7d1b) in zebrafish, followed by expression validation in mice. We then revealed that disruption of the map7d1b gene function exaggerated DIC effects in adult zebrafish. Mechanistically, the exacerbated DIC are likely conveyed by impaired autophagic degradation and elevated protein aggregation. Lastly, we identified 2 MAP7D1 gene variants associated with cardiac functional decline and heart failure in cancer patients who received doxorubicin therapy. Together, this study identifies MAP7D1 as a clinically relevant susceptibility gene to DIC and heart failure, providing useful information to stratify cancer patients with a high risk of incurring severe cardiomyopathy and heart failure after receiving chemotherapy.


Assuntos
Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Apoptose , Autofagia , Elementos de DNA Transponíveis/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca/fisiopatologia , Modelos Biológicos , Músculo Esquelético/metabolismo , Mutação/genética , Miocárdio/metabolismo , Miócitos Cardíacos/patologia , Polimorfismo de Nucleotídeo Único/genética , Agregados Proteicos , Fatores de Risco , Estresse Fisiológico
5.
Curr Med Sci ; 41(3): 474-481, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34169427

RESUMO

Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy is effective and well-tolerated for refractory or relapsed multiple myeloma (RRMM). The purpose of the present study was to analyze efficacy in RRMM patients with renal impairment treated by anti-BCMA CAR-T cell therapy. A total of 59 RRMM patients were selected, and divided into impaired renal function (IRF) group [baseline estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (n=18)] and normal renal function (NRF) group (baseline eGFR ≥ 90 mL/min/1.73 m2, n=41). For patients with IRF, eGFR at the 6th month post-CAR-T cells infusion was significantly higher than the baseline (P<0.05). The multivariate analysis showed that light chain type and beta-2 micro-globulin (beta-2M) were associated factors with the decrease of serum creatinine. Median progression-free survival (PFS) in the NRF group and IRF group was 266 days and 181 days respectively. Overall survival (OS) in the NRF group and IRF group was 877 days and 238 days respectively. There was no significant difference in the objective response rate (ORR) between the IRF group and the NRF group. It is suggested that CAR-T cells therapy could improve the renal function during the treatment of RRMM. The renal function could be more significantly improved in RRMM patients with light chain type than with other types.

6.
Curr Med Sci ; 41(3): 482-490, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34170459

RESUMO

Epstein-Barr virus (EBV) T/NK-cell lymphoproliferative diseases are characterized by clonal expansion of EBV-infected T or NK cells, including chronic active EBV infection of T/NK-cell type (CAEBV+T/NK), EBV-associated hemophagocytic lymphohistiocytosis (EBV+HLH), extranodal NK/T-cell lymphoma of nasal type (ENKTL), and aggressive NK-cell leukemia (ANKL). However, the role of inherited genetic variants to EBV+T/NK-LPDs susceptibility is still unknown. A total of 171 nonimmunosuppressed patients with EBV+T/NK-LPDs and 104 healthy donors were retrospectively collected and a targeted sequencing study covering 15 genes associated with lymphocyte cytotoxicity was performed. The 94 gene variants, mostly located in UNC13D, LYST, ITK, and PRF1 genes were detected, and mutations covered 28/50 (56.00%) of CAEBV-T/NK, 31/51 (60.78%) of EBV+HLH, 13/28 (46.42%) of ENKTL, and 13/48 (27.09%) of ANKL. Most mutations represented monoallelic and missense. Three-year overall survival rate of patients with CAEBV-T/NK and EBV+HLH was significantly lower in patients with germline mutations than in those without germline mutations (P=0.0284, P=0.0137). Our study provided novel insights into understanding a spectrum of nonimmunosuppressed EBV+T/NK-LPDs with respect to genetic defects associated with lymphocyte cytotoxicity and reminded us that the gene sequencing may be an auxiliary test for diagnosis and risk stratification of EBV+T/NK-LPDs.

7.
8.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33495363

RESUMO

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Trióxido de Arsênio/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trióxido de Arsênio/efeitos adversos , Quimioterapia de Consolidação/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento , Tretinoína/efeitos adversos
9.
BMC Cancer ; 20(1): 714, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736575

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a spectrum of disease comprising more than 30% of non-Hodgkin lymphomas. Although studies have identified several molecular subgroups, the heterogeneous genetic background of DLBCL remains ambiguous. In this study we aimed to develop a novel approach and to provide a distinctive classification system to unravel its molecular features. METHOD: A cohort of 342 patient samples diagnosed with DLBCL in our hospital were retrospectively enrolled in this study. A total of 46 genes were included in next-generation sequencing panel. Non-mutually exclusive genetic signatures for the factorization of complex genomic patterns were generated by random forest algorithm. RESULTS: A total of four non-mutually exclusive signatures were generated, including those with MYC-translocation (MYC-trans) (n = 62), with BCL2-translocation (BCL2-trans) (n = 69), with BCL6-translocation (BCL6-trans) (n = 108), and those with MYD88 and/or CD79B mutations (MC) signatures (n = 115). Comparison analysis between our model and traditional mutually exclusive Schmitz's model demonstrated consistent classification pattern. And prognostic heterogeneity existed within EZB subgroup of de novo DLBCL patients. As for prognostic impact, MYC-trans signature was an independent unfavorable prognostic factor. Furthermore, tumors carrying three different signature markers exhibited significantly inferior prognoses compared with their counterparts with no genetic signature. CONCLUSION: Compared with traditional mutually exclusive molecular sub-classification, non-mutually exclusive genetic fingerprint model generated from our study provided novel insight into not only the complex genetic features, but also the prognostic heterogeneity of DLBCL patients.


Assuntos
Algoritmos , Genes Neoplásicos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Linfoma Difuso de Grandes Células B/genética , Transcriptoma/genética , Adulto , Idoso , Inteligência Artificial , Antígenos CD79/genética , China , Estudos de Coortes , Análise Mutacional de DNA/métodos , Feminino , Genes bcl-2 , Genes myc , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/classificação , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Estudos Retrospectivos , Translocação Genética
10.
J Clin Oncol ; 38(29): 3367-3376, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650683

RESUMO

PURPOSE: The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial. PATIENTS AND METHODS: We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.5 mg/kg thymoglobulin plus cyclosporine [CsA], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (CsA, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. RESULTS: From November 2013 to April 2018, 263 patients were enrolled. The cumulative incidence rate of grade 2-4 aGVHD was significantly reduced in the ATG group (13.7%; 95% CI, 13.5% to 13.9%) compared with the control group (27.0%; 95% CI, 26.7% to 27.3%; P = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 27.6% to 28.2%] v 52.5% [95% CI, 52.1% to 52.9%]; P < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 8.4% to 8.6%] v 23.2% [95% CI, 22.9% to 23.5%]; P = .029) than the control group. There were no differences between the ATG and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality (NRM), 3-year cumulative incidence of relapse (CIR), 3-year overall survival, or 3-year leukemia-free survival. Three-year GVHD relapse-free survival was significantly improved in the ATG group (38.7%; 95% CI, 29.9% to 47.5%) compared with the control group (24.5%; 95% CI, 16.9% to 32.1%; P = .003). CONCLUSION: Our study is the first prospective RCT in our knowledge to demonstrate that ATG can effectively decrease the incidence of aGVHD after MSDT in the CsA era without affecting the CIR or NRM.


Assuntos
Soro Antilinfocitário/administração & dosagem , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Ciclosporina/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Irmãos , Doadores de Tecidos
11.
Curr Med Sci ; 39(6): 874-882, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31845217

RESUMO

As a rapidly progressing field in oncology, the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors (CARs) has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials. Of note, CAR T cell therapy has shown extraordinary potential, especially in relapsed/refractory patients. However, there are still challenges regarding the further development of this strategy, spanning from engineering and manufacturing issues, to limited applications, to accompanying toxicities. In this review, we will summarize the general knowledge of this novel method, including receptor composition, applications, adverse events and challenges. Additionally, we will propose several comprehensive recommendations.


Assuntos
Neoplasias Hematológicas/terapia , Imunoterapia Adotiva/métodos , Ensaios Clínicos como Assunto , Neoplasias Hematológicas/imunologia , Humanos , Imunoterapia Adotiva/efeitos adversos , Engenharia de Proteínas , Receptores de Antígenos Quiméricos/imunologia , Resultado do Tratamento
12.
Front Oncol ; 9: 1133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31709191

RESUMO

Background: DNA methyltransferase 3A (DNMT3A) plays a unique role in hematopoiesis and acute myeloid leukemia (AML) pathogenesis. While the influences of DNMT3A mutation subtypes are still under debate. Purpose: Exploration of the clinical and molecular differences between AML patients carrying DNMT3A R882 mutations and DNMT3A frameshift mutations. Methods: Next generation of sequencing (NGS) and clinical data of 118 AML patients in our center were analyzed and compared. NGS, mRNA and miRNA profiling and clinical data from 12 patients in TCGA database were integrative analyzed. Results: Among all patients enrolled, 113 patients were positive for the variants of interest. Overall, a total of 295 variants were discovered, among which 24 DNMT3A mutations were detected, including 1 non-sense, 20 missense, 3 frameshift mutations. And 7 DNMT3A R882 mutations (3 R882H, 2 R882C, and 2 R882P) were found. Clinical analysis from our cohort and TCGA database indicated that patients carrying DNMT3A R882 mutation exhibited significantly higher levels of peripheral blood hemoglobin and non-significantly inferior prognosis compared with patients with DNMT3A frameshift mutations. Integrative analysis indicated that miR-10b, miR-143, and miR-30a were significantly decreased in the DNMT3A R882 group. High miR-143 expression is significantly associated with better prognosis in AML patients with DNMT3A mutations. Conclusion: Different molecular and clinical characteristics existed between patients with DNMT3A variant subtypes. The distinct microRNA expression pattern for DNMT3A R882 AML patients might not only act as markers to predict disease prognosis, but also could be further investigated to develop novel therapeutic targets for patients with DNMT3A mutations.

13.
Chin J Dent Res ; 22(3): 181-188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508606

RESUMO

OBJECTIVE: To evaluate the effect of provisional restorations using ovate pontics on the hard and soft tissues of the alveolar ridge after tooth extraction. METHODS: Patients with intact buccal bone after extraction of a maxillary incisor underwent a series of treatments. The protocol included tooth extraction and provisional restoration using ovate pontics. The outcomes were assessed 1, 3 and 6 months after the procedure, regarding changes in bone volume and soft tissue dimension. RESULTS: A total of 11 patients (6 female and 5 male) were treated using an ovate pontic provisional restoration after tooth extraction. After 6 months, bone loss at level 1, 3 and 5 mm below the most coronal section of the bone crest was 2.28 ± 0.53 mm, 1.51 ± 0.30 mm and 1.46 ± 0.41 mm, respectively. Changes in bone volume of these three levels were significantly lower (P < 0.01) than changes previously reported in the literature. The mesial and distal papillae recessed 0.47 ± 0.24 mm and 0.88 ± 0.57 mm, respectively, whereas the midfacial shrinkage was 0.86 ± 0.44 mm. The dimension of the ridge contour around the socket reduced mostly at 3 and 5 mm below the coronal section and the gingival mucosa, with values of 1.68 ± 0.48 mm and 1.61 ± 0.48 mm, respectively. CONCLUSION: Using a provisional restoration with ovate pontics after tooth extraction may preserve the alveolar ridge by sustaining the soft tissue, in particular the gingival papilla.


Assuntos
Perda do Osso Alveolar , Prótese Parcial Fixa , Processo Alveolar , Feminino , Gengiva , Humanos , Masculino , Maxila , Extração Dentária
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(2): 170-174, 2019 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-31060670

RESUMO

Objective To assess the efficacy and safety of apatinib in the treatment of advanced colorectal cancer(CRC). Methods The clinical data of 16 CRC patients treated with apatinib after failure of prior lines of treatment were retrospectively analyzed in terms of objective response rate,disease control rate,progression-free survival,overall survival,adverse events,and prognostic factors. Results The efficacy was evaluable in 14 patients,among whom the objective response rate was 7.1% and the disease control rate was 50%.The median progression-free survival was 3 months(95%CI=1.57-4.42),and the median overall survival was 6.5 months(95%CI=4.10-8.89).The safety was evaluable in 16 patients,among whom the most common grade 3 adverse events were hypertensinon(37.5%)and proteinuria(25%).No grade 4 adverse event was observed.Multivariate analysis did not show any factor directly related to survival.Conclusion Apatinib may be effective in treating advanced CRC,with tolerable side effects.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Piridinas/uso terapêutico , Antineoplásicos/efeitos adversos , Humanos , Piridinas/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida
15.
Lancet Haematol ; 6(6): e328-e337, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126528

RESUMO

BACKGROUND: Anthracycline dose optimisation in the treatment of diffuse large B-cell lymphoma has rarely been tested. We aimed to find out whether R-CEOP70 was non-inferior to R-CHOP50 with less cardiotoxicity, and whether R-CEOP90 had a superior efficacy to R-CHOP50 or R-CEOP70 with acceptable toxic effects. METHODS: In this multicentre, phase 3, randomised, controlled study (NHL-001), patients with newly diagnosed diffuse large B-cell lymphoma or follicular lymphoma grade 3B were enrolled from 20 centres of the Multicenter Hematology-Oncology Programs Evaluation System in China. Young patients (16-60 years) were randomly assigned 1:1:1 (block size of six) to six courses of R-CHOP50, R-CEOP70, or R-CEOP90, and older patients (61-80 years) were assigned 1:1 (block size of four) to R-CHOP50 or R-CEOP70. Patients were randomly assigned using computer-assisted permuted-block randomisation. Investigators and patients were not masked to treatment assignment. In the R-CHOP50 group, patients were given rituximab 375 mg/m2 intravenously on day 0, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum dose 2 mg) intravenously on day 1, and prednisone 60 mg/m2 (maximum dose 100 mg) orally from day 1-5; in the R-CEOP70 group, epirubicin 70 mg/m2 replaced doxorubicin; and in the R-CEOP90 group, high dose epirubicin 90 mg/m2 replaced doxorubicin. All patients received two additional courses of rituximab 375 mg/m2 intravenously every 21 days. Consolidation radiotherapy was given to patients with bulky disease at diagnosis or residual disease at the end of treatment. The primary endpoint was 2-year progression-free survival. The non-inferiority margin for R-CEOP70 versus R-CHOP50 was defined by hazard ratio [HR] as the upper limit of its 95% CI being no greater than 1·50. Analysis of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01852435. FINDINGS: From May 15, 2013, to March 16, 2016, a total of 648 patients were enrolled, including 404 (62%) young patients (R-CHOP50 [n=135], R-CEOP70 [n=134], or R-CEOP90 [n=135]), and 244 (38%) older patients (R-CHOP50 [n=122] or R-CEOP70 [n=122]). Four patients were excluded from the study for consent withdrawal and one patient for misdiagnosis before treatment. The 2-year progression-free survival in the R-CHOP50 group was 72·5% (95% CI 66·6-77·6) and in the R-CEOP70 group was 72·4% ([66·5-77·5]; HR 1·00 [0·73-1·38]; p=0·99). The non-inferiority was met and adverse events were similar between the two groups. Fewer patients in the R-CEOP70 group (14 [13%] of 110) presented with over 10% decrease in left ventricular ejection fraction (LVEF) than those in the R-CHOP50 group (31 [29%] of 108) at 3 years after remission. For young patients, the 2-year progression-free survival in the R-CEOP90 group was 88·8% (82·1-93·1) and was significantly improved compared with the R-CHOP50 group (75·9% [67·7-82·3]; 0·44 [0·25-0·76]; p=0·0047) and the R-CEOP70 group (77·4% [69·4-83·7%]; 0·49 [0·27-0·86]; p=0·017). Grade 3-4 neutropenia occurred more frequently in the R-CEOP90 group (97 [72%] of 134) than in the R-CHOP50 group (87 [65%] of 133) and R-CEOP70 group (84 [63%] of 133) in young patients but without further increase of clinically significant infections. Fewer patients in the R-CEOP70 group (7 [11%] of 66) and in the R-CEOP90 group (10 [13%] of 79) presented with more than 10% decrease in LVEF than those in the R-CHOP50 group (17 [26%] of 66) at 3 years after remission. INTERPRETATION: R-CEOP70 could serve as an alternative regimen to R-CHOP50 with mild long-term cardiotoxicity. Young patients with diffuse large B-cell lymphoma might benefit from high-dose epirubicin. Epirubicin is an alternative drug to doxorubicin in regular R-CHOP with mild long-term cardiotoxicity. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Shanghai Commission of Science and Technology, Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of Shanghai Hospital Development Center, and Chang Jiang Scholars Program.


Assuntos
Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neutropenia/etiologia , Modelos de Riscos Proporcionais , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
16.
Curr Med Sci ; 39(2): 211-216, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016512

RESUMO

Discontinuation of tyrosine kinase inhibitor (TKI) therapy after achieving a persistent deep molecular response (DMR) is an urgently needed treatment goal for chronic myeloid leukemia (CML) patients and has been included in the National Comprehensive Cancer Network (NCCN) guidelines (version 2.2017) for CML. Indeed, various studies have confirmed the feasibility of discontinuing TKI therapy. In this study, we analyzed data from 45 CML patients who had discontinued TKI therapy. Univariate analysis was performed to predict factors that were potentially related to treatment-free remission (TFR) and identify the differences between early relapse and late relapse. Out of the 45 patients, 20 exhibited molecular relapse after a median follow-up of 18 months (range, 1-54 months), and the estimated TFR at 24 months was 40%. The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes. Our results indicate that TKI discontinuation could be successfully put into practice in China.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(5): 660-666, 2018 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-30404699

RESUMO

Objective To explore the efficacy and prognostic factors of cetuximab therapy for KRAS or all RAS wild-type(WT)metastatic colorectal cancer(mCRC).Methods We screened mCRC patients receiving at least two cycles of cetuximb and chemotherapy from those with KRAS WT(before November 2013)or all-RAS-WT(after November 2013)in the Department of Medical Oncology,Peking Union Medical College Hospital from November 2007 to December 2016. The relationship between the clinicopathological characteristics and the efficacy was retrospectively analyzed.Results A total of 60 patients were included. For the 34 patients receiving cetuximab as first-line treatment,the objective response rate(ORR)was 55.9%,and the progression-free survival and overall survival(OS)was 10 and 24 months,respectively. All-RAS-WT mCRC had significantly lower risk of progression than those with KRAS-only-WT(P=0.012),and left-sided colorectal cancer had higher ORR than right-sided colon cancer(62.1% vs. 0,P=0.033)during the first-line treatment. The median OS of the eight patients continuing cetuximab beyond first-line progression was 35.0(95%CI:23.6-46.4)months.Conclusions The efficacy of cetuximab for left-sided colorectal cancer was better than for right-sided colon cancer,and patients with all-RAS-WT have lower risk of progression than those with KRAS-only-WT. Patients benefiting from first-line cetuximab and continuing cetuximab beyond progression survive longer.


Assuntos
Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Humanos , Mutação , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
18.
Oncotarget ; 9(82): 35343-35355, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30450162

RESUMO

Anti-PD1 antibodies exhibit satisfactory efficacy in treating certain types of lymphoma. We conducted this meta-analysis to explore subtypes benefiting from this treatment and the best anti-PD1 therapeutic modalities. Methods: A quantitative meta-analysis was performed via a systematic search in PubMed, Web of Science, and The Cochrane Library. The pooled overall response rate (ORR), progression-free survival (PFS), complete remission rate (CRR), overall survival (OS) and adverse events (AEs) were calculated and compared. Data were analyzed using a random-effects meta-analysis to determine risk ratios. Heterogeneity across studies was analyzed using Q and I2 statistics. Results: Thirteen articles were selected, and 9 studies were included in the meta-analysis. There was evidence of significant heterogeneity among the studies. According to PD-L1 expression subgroup analysis, the PD-L1-positive group exhibited significantly better outcomes than the PD-L1-negative group (Z=5.481, p=0.000), with pooled ORRs of 0.74 (95% CI: 0.67-0.81) and 0.2 (95% CI: 0.11-0.3), respectively. For PD-L1-positive and PD-L1-negative patients, the pooled CRRs, PFS and OS were 0.21 (95% CI: 0.14-0.29), 0.76 (95% CI: 0.71-0.81) and 1.0 (95% CI: 0.98-1.0) and 0.05 (95% CI: 0.01-0.11), 0.20 (95% CI: 0.09-0.39) and 0.64 (95% CI: 0.45-0.80), respectively; differences were all statistically significant (Z=2.248, p=0.025; Z=3.555, p=0.000; and Z=3.039, p=0.002, respectively). The pooled incidence of treatment-related all-grade AEs and grade-3/4 AEs was 0.84 (95% CI: 0.75-0.92) and 0.21 (95% CI: 0.15-0.29), respectively. Conclusion: Patients with PD-L1 overexpression in relapsed or refractory lymphoma benefited more from anti-PD-1 therapy. Moreover, treatment with approved PD-1 inhibitors was well tolerated.

19.
Medicine (Baltimore) ; 97(45): e12750, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30407280

RESUMO

The aim of the present study was to assess the effect of Endostar and temozolomide or dacarbazine plus 5-fluorouracil (5-FU) in patients with advanced pancreatic neuroendocrine tumors (pNETs).Phase II study of 14 patients with locally advanced or metastatic well-differentiated pNETs treated between April 2013 and September 2016. Patients received temozolomide or dacarbazine plus 5-FU, and Endostar. The primary outcome was the radiographic response rate.All 14 patients had nonfunctional pNETs. Six patients received temozolomide and 8 received dacarbazine + 5-FU, combined with Endostar. Thirteen patients were assessable for treatment response: 1(7%) with complete response, 5 (39%) with partial response, 5 (39%) with stable disease, and 2 (15%) with progression. The median progression-free survival was 12 months. The most common grade 1/2 toxicities were neutropenia (43%) and leucopenia (21%).Endostar combined with temozolomide or dacarbazine + 5-FU was effective in the treatment of advanced pNETs. The combinations were well tolerated.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Endostatinas/administração & dosagem , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Recombinantes/administração & dosagem , Adulto , Idoso , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Temozolomida , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
20.
FEBS J ; 285(18): 3464-3484, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30073783

RESUMO

Craniofacial malformations are common congenital birth defects and usually caused by abnormal development of the cranial neural crest cells. Some nucleolar ribosome biogenesis factors are implicated in neural crest disorders also known as neurocristopathies. However, the underlying mechanisms linking ribosome biogenesis and neural crest cell (NCC) development remain to be elucidated. Here we report a novel zebrafish model with a CRISPR/Cas9-generated esf1 mutation, which exhibits severe NCC-derived pharyngeal cartilage loss and defects in the eyes, brain, and heart. The expression of several typical NCC markers, including sox10, dlx2a, nrp2b, crestin, vgll2a, and sox9a, was reduced in the head of the esf1 mutants, which indicates that esf1 plays a role in the development of zebrafish NCCs. We demonstrate that, similar to the yeast, loss of esf1 in zebrafish leads to defects in 18S rRNA biogenesis and ribosome biogenesis. We also show strong upregulation of p53 signaling as well as apoptosis, and poor proliferation in mutants. Inactivation of p53 rescues the early tissue defects and pharyngeal cartilage loss observed in esf1 mutants, indicating that increased cell death and pharyngeal cartilage defects observed in esf1 mutants are mediated via upregulated p53 signaling pathways. Based on transplantation analysis, we found esf1 functions in NCC in a cell autonomous fashion. Together, our results suggest that esf1 is required for NCC development and pharyngeal cartilage formation. These studies provide a potential model for investigating the relationship between ribosome biogenesis defects and craniofacial neurocristopathies.


Assuntos
Cartilagem/embriologia , Embrião não Mamífero/citologia , Proteínas Nucleares/metabolismo , Faringe/embriologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados/embriologia , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/metabolismo , Padronização Corporal , Cartilagem/metabolismo , Embrião não Mamífero/metabolismo , Mutação , Proteínas Nucleares/genética , Faringe/metabolismo , Ribossomos/metabolismo , Proteína Supressora de Tumor p53/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética
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