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1.
Jpn J Clin Oncol ; 51(1): 70-77, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33029633

RESUMO

OBJECTIVE: A phase 1 dose-escalation study of polatuzumab vedotin (pola) was conducted to assess safety, pharmacokinetics and preliminary antitumor activity of pola in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. METHODS: Patients received pola (1.0 or 1.8 mg/kg) intravenously every 21 days until disease progression or intolerance. Intra-patient dose escalation was prohibited. Tolerability was determined by the standard 3 + 3 rule. Blood sampling was performed to characterize pharmacokinetics. Antitumor activity was evaluated through computed tomography and bone marrow sampling. RESULTS: Four patients received pola 1.0 mg/kg; three received 1.8 mg/kg. Patients had follicular lymphoma (n = 4) or diffuse large B-cell lymphoma (n = 3), median age of 62 years, received a median of 3 prior therapies; six were female. Pola was well tolerated in both cohorts, with no dose-limiting toxicities observed. The most common adverse event was peripheral sensory neuropathy (n = 4). Grade 3 adverse events were cholecystitis and neutrophil count decreased (one each; both 1.0 mg/kg), and syncope and cataract (one each; both 1.8 mg/kg). The plasma half-life of antibody-conjugate monomethyl auristatin E was 4.43-7.98 days, and systemic exposure of unconjugated monomethyl auristatin E was limited in both cohorts. Four patients achieved objective responses (three complete, one partial) without disease progression during the study. CONCLUSIONS: This phase 1 dose-escalation study demonstrated that pola has an acceptable safety profile and offers encouraging antitumor activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Pola 1.8 mg/kg, the recommended phase 2 dose, was tolerable in Japanese patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoconjugados/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Feminino , Humanos , Imunoconjugados/efeitos adversos , Imunoconjugados/farmacocinética , Masculino , Pessoa de Meia-Idade , Recidiva
2.
Lancet Haematol ; 8(1): e80-e93, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357487

RESUMO

This Review focuses on the use of 18F-fluorodeoxyglucose (18F-FDG) PET in the assessment of diffuse large B-cell lymphoma, follicular lymphoma, and peripheral T-cell lymphoma. PET is important for staging and prognostication with stage migration compared with CT. Better outcomes for patients with early stage diffuse large B-cell lymphoma and follicular lymphoma suggests better delineation of disease has translated to improved outcomes in such patients beyond simple stage migration. The aim of treatment of diffuse large B-cell lymphoma and peripheral T-cell lymphoma is potential cure, during which PET is mainly used to assess remission. Interim PET can assess chemosensitivity in these lymphomas, but it does not predict treatment success sufficiently well to enable treatment modification, particularly in the absence of more effective therapies for patients who remain PET-positive on interim scanning. In follicular lymphoma, traditionally viewed as an incurable lymphoma, the aim of treatment is to control disease for several years, while maintaining quality of life. PET can predict prognosis for patients with follicular lymphoma with high tumour burden at the end of induction chemotherapy, and it is being evaluated as a platform for response-adapted treatment of follicular lymphoma.


Assuntos
Fluordesoxiglucose F18/uso terapêutico , Quimioterapia de Indução , Linfoma Folicular , Linfoma Difuso de Grandes Células B , Linfoma de Células T Periférico , Tomografia por Emissão de Pósitrons , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma de Células T Periférico/diagnóstico por imagem , Linfoma de Células T Periférico/tratamento farmacológico
3.
Clin Nucl Med ; 46(1): 1-7, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33181743

RESUMO

PURPOSE: The aim was to explore whether baseline total lesion glycolysis (TLG) can improve the prognostic value of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients treated with an R-CHOP-like regimen. MATERIALS AND METHODS: Ninety-four PG-DLBCL patients who underwent baseline PET/CT between July 2010 and May 2019 were included in this retrospective study. FDG-avid lesions in each patient were segmented to calculate the SUVmax, total metabolic tumor volume (TMTV), and TLG. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate prognosis. RESULTS: During the follow-up period of 5 to 108 months (35.3 ± 23.5 months), high TLG and a high NCCN-IPI were significantly associated with poor PFS and OS. Total lesion glycolysis and the NCCN-IPI were independent predictors of PFS and OS. Patients were stratified into 3 groups according to the combination of TLG and the NCCN-IPI for PFS (P < 0.001) and OS (P < 0.001): high-risk group (TLG > 1159.1 and NCCN-IPI 4-8) (PFS and OS, 57.7% and 61.5%, respectively, n = 42), intermediate-risk group (TLG > 1159.1 or NCCN-IPI 4-8) (PFS and OS, both 76.9%, n = 26), and low-risk group (TLG ≤ 1159.1 and NCCN-IPI 0-3) (PFS and OS, 97.6% and 100.0%, respectively, n = 26). CONCLUSIONS: Both TLG and the NCCN-IPI are independent predictors of PG-DLBCL patient survival. Moreover, the combination of TLG and the NCCN-IPI improved patient risk stratification and might help personalize therapeutic regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Glicólise/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prednisolona/farmacologia , Prednisolona/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo , Vincristina/farmacologia , Vincristina/uso terapêutico
4.
BMJ Case Rep ; 13(12)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33370928

RESUMO

We describe a case of a 71-year-old otherwise healthy man who presented to the dental clinic with the chief complaint of mobility involving his upper left molar teeth. The patient was a febrile, and clinical oral examination revealed localised grade II mobility and absence of gingival swelling, erythema or sinus tract. Orthopantogram revealed a poorly defined radiolucency involving the upper left second and third molar teeth. Surgical exploration of the involved area was performed and revealed the presence of a 'jelly like' brown tissue that fragments easily. Pathological examination confirmed the diagnosis of diffuse large B cell lymphoma.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Linfoma Difuso de Grandes Células B , Dente Serotino , Radioterapia/métodos , Mobilidade Dentária , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia/métodos , Diagnóstico Diferencial , Humanos , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Dente Serotino/diagnóstico por imagem , Dente Serotino/fisiopatologia , Dente Serotino/cirurgia , Radiografia Panorâmica/métodos , Extração Dentária/métodos , Mobilidade Dentária/diagnóstico , Mobilidade Dentária/etiologia , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(50): e23501, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327289

RESUMO

INTRODUCTION: Primary pulmonary lymphoma (PPL) is a rare extranodal lymphoma. Only 5% to 20% of patients suffering from PPL have diffuse large ß-cell lymphoma (DLBCL), and their chest computed tomography (CT) findings show single- or double-lung patchy or flocculated shadows, isolated or multifocal nodules, or masses. In this research paper, we report an older woman having multiple ground-glass nodules, who was eventually diagnosed with primary pulmonary diffuse large ß-cell lymphoma (PPDLBCL). PATIENT CONCERNS: A 69-year-old woman suffering from cough was admitted to the Second Hospital of Jilin University. DIAGNOSES: A chest CT scan showed multiple ground-glass nodules. She had received 2 weeks of antibiotic treatment, but the multiple ground-glass nodules were still present. Lung biopsy was performed by tracheoscopy, which showed non-Hodgkin diffuse large ß-cell lymphoma. INTERVENTIONS: The patient received R-CHOP-21 chemotherapy. OUTCOMES: The multiple ground-glass nodules were absorbed. CONCLUSION: The current study shows that spotting multiple ground-glass nodules in the lungs is a clear indication of the presence of PPDLBCL. It is important to spread awareness of PPDLBCL, which needs timely diagnosis and management.


Assuntos
Neoplasias Pulmonares/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tosse/etiologia , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Doxorrubicina/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Tomografia Computadorizada por Raios X , Vincristina/uso terapêutico
6.
Zhonghua Zhong Liu Za Zhi ; 42(12): 989-995, 2020 Dec 23.
Artigo em Chinês | MEDLINE | ID: mdl-33342153

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy. A variety of indicators have been identified to predict the prognosis of DLBCL. However, with the emerging new drugs and new therapeutic options in recent years, the prognostic value of these risk prediction models becomes limited, failing to accurately guide treatment. The rapid development of high throughput technologies has led to dramatic improvement in understanding of the biology of DLBCL. The emergence of various new biomarkers contributes to further understanding the pathogenesis, treatment optimization and prognostic stratification of this disease. This review summarizes the prognostic biomarkers related to DLBCL, which mainly covers the hematological, genetic and tumor microenvironment factors, aiming to provide some theoretical basis for the precision treatment of DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , Biomarcadores Tumorais , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Prognóstico
7.
Zhonghua Zhong Liu Za Zhi ; 42(12): 1034-1039, 2020 Dec 23.
Artigo em Chinês | MEDLINE | ID: mdl-33342160

RESUMO

Objective: To investigate the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitor combined with rituximab in the treatment of refractory or relapsed diffuse large B-cell lymphoma (rrDLBCL) patients. Methods: The efficacy and safety of rrDLBCL patients treated with PD-1 inhibitor combined with rituximab as salvage therapeutic regimen after initially treated with rituximab, cyclophosphamide, anthracycline, vincristine and prednisone (R-CHOP) regimen in Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College from October 2018 to Janurary 2020 were retrospectively analyzed.Patient who received at least one dose of PD-1 inhibitor combined with rituximab treatment and obtained the efficacy and safety evaluation were included. Results: A total of 22 patients were enrolled in this study. The median age was 51.5 years and the median number of prior treatment regimen was 2. The median time to progression (TTP) for the initial R-CHOP treatment was 9.3 months and the median interval time of rituximab administrations between the previous and the research regimen was 5.5 months. Patients were classified as germinal center B cell (GCB) origin (n=8), non-GCB origin (n=9) and primary mediastinal large B cell lymphoma (PMBCL, n=5). Four patients were double-expression lymphoma, one patient were triple-hit lymphoma. Nine patients had PD-L1 immunohistochemical staining and the proportion of PD-L1 positive tumor cells were 1%-90% for eight patients and negative for one patient.The objective response rate (ORR) and complete response rate (CR) were 72.7% (16/22) and 13.6% (3/22), respectively. The median progression free survival (PFS) was 8.0 (95%CI: 7.0-14.5) months, and overall survival (OS) was not reached. For the 17 patients of non-specific DLBCL, the ORR was 64.7% (11/17), the estimated median PFS was 4.0 (95%CI: 0-8.8) months, the 1-year PFS and OS rates were 39.2% (95%CI: 19.4%-43.4%)and 81.3% (95%CI: 71.4%-91.1%), respectively. All of 5 PMBCL cases achieved ORR, among them, one case was CR and 4 cases were partial responase (PR), and their PFS were 16.4, 9.3, 8.3, 7.9and 3.0 months, respectively. One patient had National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 grade 3 hypophysitis and one patient had NCI CTCAE grade 3 interstitial pneumonia. Conclusion: For rrDLBCL patients who have underwent rituximab treatment previously, PD-1 inhibitor combined with rituximab regimen shows a promising efficacy and tolerability, which can be a potential treatment option.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Receptor de Morte Celular Programada 1 , Rituximab , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1912-1918, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283719

RESUMO

OBJECTIVE: To analyze the efficacy of rituximab combined with CHOP/EPOCH regimen for treatment of diffuse large B-cell lymphoma(DLBCL) patients, and to explore the high risk factors of refractory and relapsed patients. METHODS: The clinical data of 72 patients with de novo DLBCL from December 2012 to December 2018 in the Department of Hematology, Zhongda Hospital Affiliated to Southeast University were retrospectively analyzed. The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH was analyzed, and survival analysis was conducted to explore the risk factors influencing refractory recurrence. RESULTS: 45 cases among 72 patients achieved complete remission (CR), 11 cases achieved partial remission (PR), the total remission rate was 77.78%. 25 cases (34.2%) refractory and relapsed. Single factor analysis showed that the B symptoms, low Hb, high NLR, low MLR, high ß2-MG, high ESR, high hs-CRP, high LDH, low ALB, low HDL were high risk factors of refractory and relapsed DLBCL. Multivariate Logistic analysis showed B symptoms, low Hb, high ß2-MG, high ESR, and high hs-CRP were significantly related with refractory relapse. Survival analysis showed that OS of refractory and relapsed group was significantly worse than that in remission group. In addition, OS of patients with B symptoms, anemia, low LMR, high ß2-MG, high hs-CRP, high LDH, low ALB and low HDL was significantly worse than that of control group. CONCLUSION: The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH regimen is high, but about one third of the patients still show refractory and relapsed. B Symptoms, anemia, high ß2-MG, ESR and hs-CRP are the independent prognostic factors.


Assuntos
Linfoma Difuso de Grandes Células B , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1919-1922, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283720

RESUMO

OBJECTIVE: To summarize and analyze the clinical characteristics, treatment and prognosis of acute lung injury in patients with diffuse large B-cell lymphoma (DLBCL) after chemotherapy with rituximab chemotherapy, so as to improve the understanding of the disease and guide the clinical treatment. METHODS: Twenty-Six patients with DLBCL were treated with rituximab chemotherapy and developed to acute lung injury in Third Hospital of Peking University from January 2013 to September 2018 were selected. The clinical features, imaging findings, chemotherapy course, therapeutic effect and prognosis were analyzed. RESULTS: The main clinical symptoms of patients were fever, cough and chest tightness, among which 12 patients showed hypoxia and 3 patients showed respiratory failure type I. The mainly manifested chest CT was diffusive glass grinding in both lungs, and some patients were complicated with a small amount of pleural effusion. The onset chemotherapy time was mainly distributed in 2 to 4 courses, the time between the onset of symptoms and the infusion of rituximab was 8 to 49 days. 25 patients shows no obvious limitation in daily life after effective treatment, and 1 patient died of ineffective treatment. CONCLUSION: There are no typical clinical symptoms in the early stage of acute lung injury after rituximab chemotherapy in DLBCL. Early detection and early hormone therapy are very important to achieve good therapeutic effect.


Assuntos
Lesão Pulmonar Aguda , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prognóstico , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1923-1932, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283721

RESUMO

OBJECTIVE: To evaluate the clinical value of serum amyloid A (SAA1/2) and misfolded transthyretin (TTR) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients. METHODS: 30 R/R DLBCL patients were enrolled as observation group, 20 remission/stabilization DLBCL and 10 chronic lymphadenitis patients were enrolled as control group. SELDI technique, Tris-Tricine sodium dodecyl sulfate-polyacrylamide gel electro-phoresis, the shotgun-LTQ-MS method, and bioinformatics technique were used to detected and analyzed SAA and TTR in R/R DLBCL patients. SPSS 21.0 software was used to analyze the relationship between the high expression of SAA, misfolded TTR in serum and the clinicopathological features, survival time of R/R DLBCL. patients Chi-square test was used to analyze clinical count data, Kaplan-Meier curve was used for survival analysis, and Log-Rank test was used to compare single-factor survival differences. RESULTS: The high expression of SAA and TTR (SAA+TTR+) was significantly associated with extranodal lesion, high level of LDH, and NCCN-IPI scores, and also correlated with non-GCB type. TTR+ was correlated with C-MYC in pathological tissue, while SAA+ was also associated with B-symptoms. The survival time of patients in SAA+, TTR+, and SAA+TTR+ group were shorter than that in control group. CONCLUSION: Both SAA and misfolded TTR are poor prognosis factors of R/R DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B , Pré-Albumina , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pacientes , Pré-Albumina/uso terapêutico , Prognóstico , Proteína Amiloide A Sérica
11.
Zhonghua Yi Xue Za Zhi ; 100(42): 3296-3302, 2020 Nov 17.
Artigo em Chinês | MEDLINE | ID: mdl-33202490

RESUMO

Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage Ⅲ or Ⅳ, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade Ⅲ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
12.
Nat Commun ; 11(1): 6004, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33244018

RESUMO

Diagnostic histopathology is a gold standard for diagnosing hematopoietic malignancies. Pathologic diagnosis requires labor-intensive reading of a large number of tissue slides with high diagnostic accuracy equal or close to 100 percent to guide treatment options, but this requirement is difficult to meet. Although artificial intelligence (AI) helps to reduce the labor of reading pathologic slides, diagnostic accuracy has not reached a clinically usable level. Establishment of an AI model often demands big datasets and an ability to handle large variations in sample preparation and image collection. Here, we establish a highly accurate deep learning platform, consisting of multiple convolutional neural networks, to classify pathologic images by using smaller datasets. We analyze human diffuse large B-cell lymphoma (DLBCL) and non-DLBCL pathologic images from three hospitals separately using AI models, and obtain a diagnostic rate of close to 100 percent (100% for hospital A, 99.71% for hospital B and 100% for hospital C). The technical variability introduced by slide preparation and image collection reduces AI model performance in cross-hospital tests, but the 100% diagnostic accuracy is maintained after its elimination. It is now clinically practical to utilize deep learning models for diagnosis of DLBCL and ultimately other human hematopoietic malignancies.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Biópsia , Corantes/química , Diagnóstico Diferencial , Amarelo de Eosina-(YS)/química , Estudos de Viabilidade , Hematoxilina/química , Hospitais , Humanos , Linfoma Difuso de Grandes Células B/patologia , Microscopia , Coloração e Rotulagem/métodos
13.
PLoS One ; 15(11): e0241634, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33180881

RESUMO

AIM: Lymphoplasmacytic lymphoma (LPL) is an indolent mature B-cell-neoplasm with involvement of the bone marrow. At least 90% of LPLs carry MYD88-L265P mutation and some of them (~10%) transform into diffuse large B-cell-lymphoma (DLBCL). MATERIAL AND METHODS: Over the past 15 years we have collected 7 cases where the both LPL and DLBCL were diagnosed in the same patient. Clinical records, analytical data and histopathological specimens were reviewed. FISH studies on paraffin-embedded tissue for MYC, BCL2 and BCL6 genes were performed, as well as MYD88-L265P mutation and IGH rearrangement analysis by PCR. A mutational study was done by massive next generation sequencing (NGS). RESULTS: There were 4 women and 3 men between 36-91 years of age. Diagnoses were made simultaneously in 4 patients. In two cases the LPL appeared before the DLBCL and in the remaining case the high-grade component was discovered 5 years before the LPL. In 6 cases both samples shared the MYD88-L265P mutation. IGH rearrangement analysis showed overlapping features in two of 6 cases tested. Mutational study was evaluable in three cases for both samples showing shared and divergent mutations. CONCLUSIONS: These data suggest different mechanisms of DLBCL development in LPL patients.


Assuntos
Heterogeneidade Genética , Linfoma Difuso de Grandes Células B/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Evolução Clonal , Progressão da Doença , Feminino , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Fator 88 de Diferenciação Mieloide/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética
14.
Nat Genet ; 52(11): 1247-1255, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33077914

RESUMO

Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes is fundamental to understanding of evolutionary and regulatory mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity (CHESS), an algorithm for the comparison of chromatin contact maps and automatic differential feature extraction. We demonstrate the robustness of CHESS to experimental variability and showcase its biological applications on (1) interspecies comparisons of syntenic regions in human and mouse models; (2) intraspecies identification of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and (4) the systematic identification of chromatin contact differences in high-resolution Capture-C data. In summary, CHESS is a computationally efficient method for the comparison and classification of changes in chromatin contact data.


Assuntos
Algoritmos , Cromatina , Animais , Cromatina/química , Cromatina/fisiologia , Drosophila , Humanos , Processamento de Imagem Assistida por Computador , Linfoma Difuso de Grandes Células B/genética , Camundongos , Modelos Genéticos , Conformação Proteica , Relação Quantitativa Estrutura-Atividade , Especificidade da Espécie
16.
Medicine (Baltimore) ; 99(43): e22510, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120740

RESUMO

INTRODUCTION: Chimeric antigen receptor T cells (CAR-T) targeting CD19 have shown great potential for treatment of B-cell malignancies. For those patients who can not achieve complete remission (CR) or suffer from relapse after CAR-T therapy, further therapeutic strategies still remain elusive. Whether existing CAR-T cells can revitalize in vivo and eradicate tumor cells is still unknown. PATIENT CONCERNS: We report a case of diffused large B-cell lymphoma patient who had achieved CR after CD19 targeted CAR-T therapy but relapsed after 5 months. DIAGNOSIS: Five months after CAR-T cell infusion, the patient was confirmed a relapse by follow-up PET/CT scan and a mass biopsy. Flow cytometry showed a dramatically decreased percentage of CAR-T cells in peripheral blood (PB). INTERVENTIONS: A second anti-CD19 CAR-T therapy was planned with deliberation. Firstly, the patient received lymphodepletion chemotherapy with fludarabine (25 mg/m, d1-d3) and cyclophosphamide (500 mg/m d2-d3). OUTCOMES: After fludarabine and cyclophosphamide (FC) lymphodepletion chemotherapy, pre-existing CAR-T cells were revitalized and the patient developed grade 2 cytokine release syndrome (CRS) contributing to the regression of relapsed B-cell lymphoma. CONCLUSIONS: This case suggested that FC chemotherapy could revitalize CAR-T cells contributing to the regression of relapsed B-cell lymphoma. Nevertheless, further researches are required in the future as this report described only a single case.


Assuntos
Ciclofosfamida/uso terapêutico , Depleção Linfocítica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão , Linfócitos T/imunologia , Vidarabina/análogos & derivados , Adulto , Antígenos CD19/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Síndrome da Liberação de Citocina/etiologia , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Vidarabina/uso terapêutico
17.
Medicine (Baltimore) ; 99(43): e22788, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120793

RESUMO

RATIONALE: The prognosis of patients with aggressive relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) remains poor. Both immunomodulatory drugs and histone deacetylase inhibitors have demonstrated activity against R/R NHL; yet, the combination of these 2 targeted therapies has rarely been explored. PATIENT CONCERNS: Here, we report 3 cases. Case 1 was a 68-year-old woman who presented to our hospital with dyspnea. Case 2 was a 75-year-old man with massive upper gastrointestinal bleeding. Case 3 was a 62-year-old woman with cough, dyspnea, and lymphadenopathy. DIAGNOSIS: The biopsy results revealed diffuse large B cell lymphoma (DLBCL), DLBCL, and angioimmunoblastic T-cell lymphoma, for Case 1, 2, and 3 respectively. INTERVENTION: All 3 patients experienced relapse after first-line therapy and multiple lines of salvage therapy. Finally, they all received lenalidomide combined with chidamide. OUTCOMES: All 3 patients achieved complete and durable remission. Case 1 relapsed again after 3 months, while the other 2 cases remained in complete remission. LESSONS: To our knowledge, this is the first report of lenalidomide combined with chidamide for the treatment of R/R NHL. Our findings warrant further evaluation of this novel chemo-free therapy in future prospective clinical trials.


Assuntos
Aminopiridinas/uso terapêutico , Benzamidas/uso terapêutico , Lenalidomida/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Aminopiridinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/administração & dosagem , Feminino , Humanos , Lenalidomida/administração & dosagem , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Terapia de Salvação
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1570-1577, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067956

RESUMO

AbstractObjective:To investigate the expression of miR-215 and KDM1B in DLBCL patients, and to analysis its clinical significance. METHODS: Fifty patients with DLBCL treated in our hospital were selected as DLBCL group, and 30 cases of reactive proliferative lymphadenitis(RPL) were selected as controls. RQ-PCR was used to detect the expression level of miR-215, and immunohistochemistry was used to detect the expression of KDM1B protein. The expression of miR-215 and KDM1B in patients with different clinical characteristics and the survival rate of patients with different expression of miR-215 and KDM1B was compared. miR-215 mimics was transfected into SU-DHL-4 cells. Cell proliferation was detected by CCK-8. Cell apoptosis was measured by flow cytometry. The expression of KDM1B protein was detected by Western blot. RESULTS: The expression of miR-215 in DLBCL patients was significantly lower than that in control group, and the positive expression of KDM1B protein was higher, the difference was statistically significant(P<0.01). Spearman rank correlation analysis showed that the expression of miR-215 negatively correlated with KDM1B (r=-0.751,P<0.05). There was significant correlation of miR-215, KDM1B expression with symptoms of B,Serum level of LDH, International Prognostic Index(IPI), Ann Arbor stage,Tumor size, respectively in patients(P<0.05). Kaplan-Meier showed that 5-year overall survival rate of patients with high miR-215 expression was significantly longer than that with low miR-215 expression (P=0.013). The 5-year survival rate of the patients with high positive KDM1B expression was significantly lower than that with low positive expression(P=0.024). KDM1B protein was suppressed by the transfection of miR-215 mimics for 72 h, the cell proliferation rate in miR-215 mimics group was significantly lower than that in control group and NC mimics group (P<0.05), but cell apoptotic rate of miR-215 mimics were significantly higher(P<0.05). The expression of KDM1B protein was significantly lower than that in control and NC group(P<0.05). CONCLUSION: There are low expression of miR-215 and high expression of KDM1B protein in patients with DLBCL, suggesting that they may be the diagnostic and prognostic indicators of DLBCL. miR-215 can directly target KDM1B to inhibit cell growth and induce apoptosis.


Assuntos
Linfoma Difuso de Grandes Células B , MicroRNAs , Apoptose , Proliferação de Células , Humanos , Oxirredutases N-Desmetilantes , Prognóstico
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1551-1557, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067953

RESUMO

OBJECTIVE: To investigate the clinical characteristics of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and the factors affecting overall survival (OS) time. METHODS: The clinical data of 14 R/R DLBCL patients admitted to the Hainan Hospital of Chinese PLA General Hospital from April 2012 to March 2019 were analyzed retrospectively and the overall response rate (ORR) after the end of different treatments was estimated. Kaplan-Meier method was used to describe the survival curve, and Log-rank test was used to compare whether different survival curves showed statistically different. RESULTS: There were 8 males and 6 females with a median age of 51 (26-75) years old and the median course of treatment before R/R was 7 (4-13). Finally, 11 patients achieved remission, 6 patients of which showed complete remission, and 5 patients showed partial remission, with the median ORR duration at 2.5 (0-51) months. All patients in the group of ibrutinib combined with second-line chemotherapy achieved remission (4/4), it was equivalent to the high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC-AHSCT) group (4/4), which was significantly higher than that of the other second-line group (3/6). The median OS time of patients was 17 (6-76) months. The survival of patients receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT was significantly better than that of patients not receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT. Normal lactate dehydrogenase, IPI score<3 at diagnosis, and CR/PR after treatment could improve the survival time of patients. CONCLUSION: The duration of remission for R/R DLBCL patients is short and the prognosis is very poor. The survival time of patients with high level of lactate dehydrogenase, IPI score≥3 at diagnosis and SD/PD after treatment is significantly shortened. Ibrutinib combined second-line chemotherapy and HDC-AHSCT can improve the efficacy and survival of R/R DLBCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Autólogo
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