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3.
Medicine (Baltimore) ; 99(33): e21736, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872060

RESUMO

RATIONALE: Pilot studies have reported that patients with systemic lupus erythematosus (SLE) appear more likely to develop into neoplasia, especially lymphatic hyperplasia diseases. To our knowledge, this is the first case report of the concomitant onset of SLE and primary breast diffuse large B-cell lymphoma (PB-DLBCL). PATIENT CONCERNS: We reported an unusual case of the occurrence of primary breast diffuse large B-cell lymphoma in a 25-year-old female patient who had been diagnosed with SLE and treated with immunosuppressive drugs for about 4 years. She presented a 7-week history of a painless mass above the left breast and no history suggestive of any nipple discharge, fever, and weight loss. DIAGNOSIS: Ultrasonography of the breast showed that there was 1 mass in the left breast. After breast mass surgical resection, histopathological examinations were performed and revealed that it was primary breast diffuse large B-cell lymphoma. INTERVENTIONS: Treatment strategy with vincristine and dexamethasone was used to improve symptoms. However, the patient's renal function deteriorated and the blood potassium rose continuously and she and their family members refused the follow-up treatments. OUTCOMES: The patient died 8 months after she was discharged from the hospital. LESSONS: PB-DLBCL is a rare occurrence in SLE patients. Therefore, a careful examination is very important in SLE cohort, as activity of the disease and malignancy may mimic each other. Meanwhile, when symptoms cannot be explained or insensitive to treatment, the occurrence of malignant tumors must be highly considered.


Assuntos
Neoplasias da Mama/complicações , Mama/patologia , Falência Renal Crônica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Linfoma Difuso de Grandes Células B/complicações , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Evolução Fatal , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Radiografia , Ultrassonografia
4.
Medicine (Baltimore) ; 99(35): e21704, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871888

RESUMO

To explore the relationship between C3435T polymorphism of multi-drug resistance gene (MDR1) gene and susceptibility, clinicopathological characteristics, curative effect and hematological toxicity of diffuse large B-cell lymphoma (DLBCL) in XinJiang.The peripheral venous blood samples of 54 patients with DLBCL and 60 healthy controls were collected. The alleles and genotypes of MDR1 gene C3435T were detected by DNA direct extraction with PCR technique, and the frequency of C3435T allele and genotypes were detected by the chi-square test. The relationship between the allele and genotype distribution of C3435T locus and the susceptibility, clinicopathological characteristics, curative effect and hematological toxicity of DLBCL were analyzed.1 the frequency of CT heterozygote and CC homozygote mutation was significantly higher in the case group (46.3% in CT genotype and 42.6% in CC genotype) compared to the control group (P < 0.05). The frequency of CC genotype mutation in the case group was 42.6%, which was significantly higher than that in the control group (P < 0.05, OR 3.209, 95% CI: 1.288-7.997). 2 the genotypes of C3435T locus of MDR1 gene were distributed in age, sex, nationality, pathological characteristics, clinical-stage, IPI index, B symptoms, infection with EB virus, clinicopathological characteristics and clinical efficacy of hepatitis B in patients with DLBCL. There was no significant difference in myelosuppression (P > 0.05).The homozygous mutation genotype of CC is the risk genotype of DLBCL. The alleles and genotypes are not associated with the clinicopathological characteristics, efficacy and myelosuppression toxicity of DLBCL.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , China , Feminino , Heterozigoto , Homozigoto , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
5.
Medicine (Baltimore) ; 99(35): e21844, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871907

RESUMO

RATIONALE: The heart transplantation is the most important treatment for patients with end-stage severe heart disease who failed to conventional therapy. Post-transplant lymphoproliferative disorder is the second most common malignancy in heart transplant recipients. However, primary central nervous system lymphoma (PCNSL) after heart transplantation is an extremely rare condition. PATIENTS CONCERNS: This report described a 53-year-old male who was diagnosed as PCNSL 17 months after heart transplantation. DIAGNOSES: The patient was admitted to the local hospital presenting with dizziness, headache, and reduced left-sided power and sensation for 1 week. He had a medical history of heart transplantation because of the dilated cardiomyopathy 17 months ago and had a 17-month history of immunosuppressive therapy with tacrolimus. A computed tomography scan of the brain revealed a bulky mass in the right temporal lobe. The emergency intracranial mass resection and cerebral decompression were performed in our hospital. The histopathology of the brain lesions showed diffuse large B-cell lymphoma. A further FDG positron emission tomography-computed tomography scan of the whole body showed no significantly increased metabolic activity in other regions. The final diagnosis of this patient was PCNSL after heart transplantation. INTERVENTIONS: Given the poor health condition, with the patient's consent, the whole brain radiotherapy was performed with supportive care. OUTCOMES: The disease deteriorated rapidly during the period of receiving radiotherapy, and he died within 2 months from the diagnosis. LESSONS: PCNSL after heart transplantation is an extremely rare phenomenon with extremely poor prognosis. We should pay close attention to the heart recipients, especially when the patients present with neurological symptoms and signs. The available treatment options for PCNS-post-transplant lymphoproliferative disorder include the reduction of immunosuppressive drugs, immune-chemotherapy, operation, radiotherapy. However, individual treatments for heart transplant recipients with PCNSL should be based on the performance status and tolerance to treatment, combined with the doctor's experience and supportive care.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Transplante de Coração , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Tacrolimo/uso terapêutico , Tomografia Computadorizada por Raios X
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1189-1196, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798397

RESUMO

OBJECTIVE: To investigate the prognosis prediction value of PET/CT in DLBCL patients treated with CAR-T therapy. METHODS: The effects of PET/CT were retrospectively explored on 13 R/R DLBCL patients who were treated with CAR-T therapy. Parameters reflecting tumor metabolic burden, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured before and after CAR-T treatment. RESULTS: Patients with larger baseline MTV or longer sum of longest diameters showed shorter overall survival (OS) time than those with low tumor burden. Patients achieved complete remission (CR), partial remission (PR) and minor remission (MR) determined by response evaluation criteria in lymphoma (RECIL) in 12 weeks showed progression-free survival and OS time superior to those of patients with no remission. In addition, it was found that 2 patients with residual masses classified as PR by contrast-enhanced CT of patients were evaluated as complete metabolic response by PET/CT imaging. CONCLUSION: PET/CT shows a great value in the evaluation of prognosis and response in CAR-T-treated R/R DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Terapia Baseada em Transplante de Células e Tecidos , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons , Prognóstico , Receptores de Antígenos Quiméricos , Estudos Retrospectivos
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1210-1214, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798400

RESUMO

OBJECTIVE: To analyze the clinical efficacy and safety of rituximab therapy for patients with Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL), and to explore the factors influencing the clinical efficacy. METHODS: According to therapeutic regimen, 66 patients with EBV-positive DLBCL were divided into two groups: CHOP group (32 cases) and R-CHOP group (CHOP+ rituximab, 34 cases). The clinical efficacy and the incidence of complication were compared between two groups. The clinical risk factors for the clinical efficacy in patients with EBV-positive DLBCL were confirmed by multivariate Logistic analysis. RESULTS: Compared with CHOP group, the complete remission rate, partial remission rate and the overall effective rate in R-CHOP group all were high (P<0.05), moreover the disease progression rate in R-CHOP group were low (P<0.05). The occurrences rate of myelotoxicity, hepatic injury and gastrointestinal reaction were not statistically significantly different between two groups (P>0.05). Multivariate Logistic analysis showed that the Ann Arbor staging, IPI risk score and Ki-67 positive rate were independent risk factors for the clinical efficacy in patients with EBV-positive DLBCL (OR=2.689, P=0.038; OR=3.232, P=0.025; OR=2.919, P=0.023). CONCLUSION: The clinical efficacy and safety of the therapy with rituximab on the patients with EBV-positive DLBCL are better. The poor Ann Arbor stage, high IPI risk score and the Ki-67 positive rate are factors affecting the clinical efficacy for the patients with EBV-positive DLBCL.


Assuntos
Herpesvirus Humano 4 , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
9.
Lancet Haematol ; 7(9): e649-e659, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32758434

RESUMO

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


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidonas/uso terapêutico , Quinazolinonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/patologia , Piperidonas/efeitos adversos , Piperidonas/farmacocinética , Quinazolinonas/efeitos adversos , Quinazolinonas/farmacocinética , Recidiva , Índice de Gravidade de Doença , Trombocitopenia/etiologia , Trombocitopenia/patologia , Resultado do Tratamento
10.
Gerodontology ; 37(3): 307-311, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32809252

RESUMO

INTRODUCTION: Lymphomas are a heterogeneous group of malignant neoplasms of lymphocytes and their precursor cells. Lymphoma is seen 3.5% of all intraoral malignancies and is the second most common neoplasm after the squamous cell carcinoma in the head and neck region. Diffuse large B-cell lymphomas (DLBCL), which is a subtype of non-Hodgkin lymphoma, are seen mostly in the paraoral region. CASE PRESENTATION: An 82-year-old woman was referred with a localised swelling of the mandibular buccal mucosa for 3 months. Excisional biopsy revealed the diagnosis of DLBCL in the mandible and chemotherapy regimen started immediately. However, patient died during treatment. CONCLUSIONS: Non-Hodgkin's lymphomas would be late- or misdiagnosed in the perioral region that may result poor prognosis.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Mandíbula , Mucosa Bucal
11.
Nat Commun ; 11(1): 3651, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686676

RESUMO

Lesion-based targeting strategies underlie cancer precision medicine. However, biological principles - such as cellular senescence - remain difficult to implement in molecularly informed treatment decisions. Functional analyses in syngeneic mouse models and cross-species validation in patient datasets might uncover clinically relevant genetics of biological response programs. Here, we show that chemotherapy-exposed primary Eµ-myc transgenic lymphomas - with and without defined genetic lesions - recapitulate molecular signatures of patients with diffuse large B-cell lymphoma (DLBCL). Importantly, we interrogate the murine lymphoma capacity to senesce and its epigenetic control via the histone H3 lysine 9 (H3K9)-methyltransferase Suv(ar)39h1 and H3K9me3-active demethylases by loss- and gain-of-function genetics, and an unbiased clinical trial-like approach. A mouse-derived senescence-indicating gene signature, termed "SUVARness", as well as high-level H3K9me3 lymphoma expression, predict favorable DLBCL patient outcome. Our data support the use of functional genetics in transgenic mouse models to incorporate basic biology knowledge into cancer precision medicine in the clinic.


Assuntos
Senescência Celular , Histona Metiltransferases , Linfoma Difuso de Grandes Células B , Células 3T3 , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Epigênese Genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Histona Metiltransferases/genética , Histona Metiltransferases/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Camundongos , Camundongos Transgênicos , Prognóstico
12.
PLoS One ; 15(7): e0235786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32639975

RESUMO

In front-line treatment of diffuse large B-cell lymphoma (DLBCL), prior studies suggest that concordant but not discordant involvement of the bone marrow (BM) portends a poor prognosis. The prognostic impact of bone marrow infiltration (BMI) in recurrent or refractory DLBCL (r/rDLBCL) and transformed indolent lymphoma (r/rTRIL) patients is less clear. Thus, we examined the prognostic significance of the infiltration of bone marrow (BMI) by concordant, large B-cells (conBMI) and discordant, small B-cells (disBMI) in this patient group. We performed a single center retrospective analysis of the prognostic impact of BMI diagnosed before start of second-line treatment as well as multiple clinicopathologic variables in 82 patients with r/rDLBCL or r/rTRIL intended to treat with autologous SCT. Twenty-five of 82 patients (30.5%) had BMI. Out of these, 19 (76%) had conBMI and 6 (24%) had disBMI. In patients with conBMI but not disBMI, uni- and multivariate analysis revealed inferior progression free survival (PFS) and overall survival (OS) compared to patients without BMI (median PFS, 9.2 vs 17.45 months, log rank: p = 0.049; Hazard Ratio, 2.34 (Confidence Interval, 1.24-4.44), p = 0.009; median OS 14.72 vs 28.91 months, log rank: p = 0.017; Hazard Ratio, 2.76 (Confidence Interval, 1.43-5.31), p = 0.002). ConBMI was strongly associated with nonGCB subtype as classified by the Hans algorithm (82.4% vs 17.6%, p = 0.01). ConBMI comprised an independent predictor of poor prognosis in primary and secondary r/rDLBCL. Incorporating conBMI in the pretherapeutic risk assessment for r/rDLBCL and r/rTRIL patients may be useful for prognostication, for stratification in clinical trials, and to assess new therapies for this high-risk patient subset that might not benefit from SCT in second-line treatment.


Assuntos
Medula Óssea/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Linfócitos B/patologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
13.
Tokai J Exp Clin Med ; 45(2): 58-62, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32602102

RESUMO

Here, we report the case of cutaneous metastases from testicular diffuse large B-cell malignant lymphoma (DLBCL) concurrent with Bowen disease evaluated with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT). A 60-year-old male underwent orchiectomy to remove his left testicle because of DLBCL. Multiple skin lesions appeared 1 month postoperatively. Furthermore, an intractable erythematous plaque localized to the right lower leg was present from 2 years before the operation. 18F-FDG PET-CT images revealed multiple skin lesions with marked FDG uptakes in the face, neck, and thigh of this patient, as well as a lower leg lesion with minimal FDG uptake. Biopsy of both lesions revealed cutaneous metastases from DLBCL and Bowen disease (BD) of the lower leg lesion. 18F-FDG PET-CT images following chemotherapy and resection of BD demonstrated no FDG uptake.


Assuntos
Doença de Bowen , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/terapia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/secundário , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/terapia , Doença de Bowen/cirurgia , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos
14.
Ann Hematol ; 99(9): 2125-2132, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32613279

RESUMO

High-grade B cell lymphomas with rearrangements on C-MYC and BCL2 and/or BCL6 (HGBL with MYC and BCL2 and/or Bcl6 rearrangement) are associated with worse clinical outcomes and thus were introduced as a separate new category in the recently updated WHO classification. From 2012 to 2016, we analyzed a consecutive cohort of large B cell lymphomas (LBCLs) for C-MYC, BCL2, and BCL6 rearrangements and correlated our results with clinical-pathological parameters. Ten of 78 (13%) cases had a C-MYC and BCL2 and/or BCL6 rearrangement, so-called double or triple hit (DH), while double/triple copy number gains (CNGs) were found in eight (10%) patients. Patients with a high-grade lymphoma with DH or CNG progressed significantly more often after first-line chemotherapy (p = 0.005). When treated with standard chemotherapy, patients with a DH or CNG had a significantly worse overall (OS) and recurrence free survival (RFS) compared with all other patients (p = 0.033 and p < 0.001, respectively). Thus, patients with a diffuse large B cell lymphoma, harboring a double/triple CNG, seem to have a similar poor prognosis than those with a DH. Though our data can only be regarded as preliminary, our results warrant further investigations to fully elucidate the role of CNGs as well as underlying molecular mechanisms resulting in aggressive behavior in LBCL.


Assuntos
Variações do Número de Cópias de DNA/genética , Proteínas de Ligação a DNA/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/mortalidade , Prognóstico , Estudos Retrospectivos
15.
Medicine (Baltimore) ; 99(28): e20938, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664092

RESUMO

RATIONALE: Primary adrenal lymphoma (PAL) is an extremely rare and highly invasive malignant disease. Imaging examination usually shows bilateral adrenal involvement with large tumor masses and local infiltration. However, it is unclear how lymphoma dynamically develops into huge tumor masses in the adrenal glands. The overall survival rate of PAL is generally poor, and the underlying mechanism might be related to prooncogenic mutation but not fully elucidated. PATIENT CONCERNS: A 52-year-old woman complaining of a large mass in the left adrenal region for 1 month was admitted to our department. DIAGNOSIS: Computed tomography firstly showed a huge mass (8.9 × 7.5 cm) in the left adrenal gland and diffusely enlarged right adrenal gland. A month later, the mass in the left adrenal gland further enlarged (9.5x7.5 cm) with infiltration of the left renal artery and retroperitoneal lymphadenopathy, and the right adrenal gland rapidly progressed into a huge mass (8.0x4.7 cm). Additionally, her chest computed tomography revealed mediastinal and bilateral hilar lymphadenopathy. Then an adrenal biopsy confirmed the diagnosis of diffuse large B-cell lymphoma, nongerminal center B-cell type, stage IV by Ann Arbor staging system. Immunohistochemistry showed positivity for Ki-67 (approximately 90%), BCL2 (approximately 80%) and MYC (approximately 70%) double-expressor lymphoma. INTERVENTIONS: The patient's condition progressed rapidly, there was no opportunity to use pathology-based chemotherapy. Dexamethasone was given intravenously by thoracic and intraperitoneal injection; antibiotics and supporting treatment were also given. OUTCOMES: The patient's condition progressed rapidly, with the development of malignant chest and abdominal cavity fluid and lung infection, and eventually developed septic shock and respiratory failure. She responded poorly to treatment regimens, and eventually died 8 days after the diagnosis of PAL. LESSONS: PAL grows progressively throughout the adrenal glands, high Ki-67 positivity and BCL2/ MYC co-expression predict rapid progress and poor prognosis.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Linfoma Difuso de Grandes Células B/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica
16.
Anticancer Res ; 40(7): 3781-3792, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32620617

RESUMO

BACKGROUND/AIM: Canine B-cell lymphoma represents a useful in vivo model for human diffuse large B-cell lymphoma (DLBCL). Pan-Bromodomain and extra-terminal (BET) inhibition targeting BRD2/3/4 and selective inhibition of BRD4, as well as spleen tyrosine kinase (SYK) inhibition, are currently evaluated as haematologic cancer therapy. Herein, we characterized the differences in the biologic response of isoform-specific or pan-BET inhibition alone or in combination with SYK inhibition. MATERIALS AND METHODS: I-BET151 (pan-inhibitor) and AZD5153 (BRD4 inhibitor) were combined with Entospletinib (SYK inhibitor) and comparatively analysed in the canine DLBCL cell line CLBL-1. Dose- and time-dependent cellular responses were analysed by cell number, metabolic activity, apoptosis/necrosis, and cell morphology. The synergistic potential was evaluated through the Bliss independence model. RESULTS: I-BET151 and AZD5153 showed significant dose- and time-dependent inhibitory effects. Adding Entospletinib to I-BET151 or AZD5153 had no additional synergistic effects. CONCLUSION: Entospletinib did not enhance the inhibitory effects of the pan- or isoform-specific BET.


Assuntos
Indazóis/farmacologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteínas Nucleares/antagonistas & inibidores , Isoformas de Proteínas/antagonistas & inibidores , Pirazinas/farmacologia , Animais , Linhagem Celular Tumoral , Cães , Compostos Heterocíclicos com 2 Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Linfoma Difuso de Grandes Células B/metabolismo , Piperazinas/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Quinase Syk/metabolismo
17.
Medicine (Baltimore) ; 99(21): e19883, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481253

RESUMO

Although Indoleamine 2,3-dioxygenase (IDO), tryptophan-2,3-dioxygenase (TDO), and aryl hydrocarbon receptor (AHR) are involved in cancer immune escape, their prognostic impact on diffuse large B-cell lymphoma (DLBCL) is unknown.To examine the prognostic impact of IDO, TDO, and AHR on patients with DLBCL.This was a retrospective study on treatment-naïve patients with newly diagnosed DLBCL at the Henan Province People's Hospital between 01/2012 and 06/2015. Patients with inflammatory reactive lymph nodes were included as controls. All cases were reviewed by 2 pathologists. IDO, TDO, and AHR positivity was determined through immunochemistry. Survival was examined using the Kaplan-Meier method and multivariable Cox analyses.The positive expression of TDO (50.0% vs 16.7%, P = .005) and AHR (60.0% vs 8.3%, P < .001) were higher in DLBCL than in inflammatory control. The overall survival of IDO, TDO, and AHR positive expression in DLBCL patients was 34.6, 26.7, and 32.2 months, respectively, which is significantly shorter than that of the corresponding negative patients (49.0 months, P = .04; 58.2 months, P < .001; 58.0 months, P < .001; respectively). The multivariable analysis showed that TDO expression and Ann-Arbor stage were independently associated with PFS (TDO: HR = 8.347, 95%CI: 2.992-23.289, P < .001; stage: HR = 2.729, 95%CI: 1.571-4.739, P < .001) and OS (TDO: HR = 9.953, 95%CI: 3.228-30.686, P < .001; stage: HR = 2.681, 95%CI: 1.524-4.719, P = .001) in DLBCL patients.Overexpression of IDO, TDO, and AHR is associated with poor survival of patients with DLBCL and could be involved in the immune escape of cancer cells. Further studies are necessary to determine whether these proteins can be targeted by treatment regimens.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Indolamina-Pirrol 2,3,-Dioxigenase/fisiologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Receptores de Hidrocarboneto Arílico/fisiologia , Rituximab/uso terapêutico , Triptofano Oxigenase/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de Hidrocarboneto Arílico/biossíntese , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Triptofano Oxigenase/biossíntese , Adulto Jovem
18.
Clin Nucl Med ; 45(8): e383-e385, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32520513

RESUMO

The incidence of COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, is rapidly growing worldwide. In this pandemic period, the chance of incidental pulmonary findings suggestive of COVID-19 at F-FDG PET/CT in asymptomatic oncological patients is not negligible. To suspect COVID-19 is more demanding whether its presentation is atypical. We describe the incidental PET/CT detection of an F-FDG-avid isolated centrilobular pulmonary consolidation in an asymptomatic lymphoma patient, which later resulted in an unexpected and atypical COVID-19 presentation. The nuclear medicine physicians should be prepared to suspect COVID-19 even in asymptomatic patients presenting with a "far-from-COVID-19" finding at PET/CT.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/complicações , Pneumonia Viral/diagnóstico por imagem , Infecções por Coronavirus/complicações , Fluordesoxiglucose F18 , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
19.
Ann Hematol ; 99(8): 1823-1831, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32577843

RESUMO

Although overall survival in diffuse large B cell lymphomas (DLBCL) has improved, central nervous system (CNS) relapse is still a fatal complication of DLBCL. For this reason, CNS prophylaxis is recommended for patients at high risk of CNS disease. However, no consensus exists on definition of high-risk patient and optimal CNS prophylaxis. Systemic high-dose methotrexate in combination with R-CHOP has been suggested as a potential prophylactic method, since methotrexate penetrates the blood-brain barrier and achieves high concentration in the CNS. In this retrospective analysis, we report treatment outcome of 95 high-risk DLBCL/FL grade 3B patients treated with R-CHOP or its derivatives with (N = 57) or without (N = 38) CNS prophylaxis. At a median follow-up time (51 months), CNS relapses were detected in twelve patients (12.6%). Ten out of twelve (83%) of CNS events were confined to CNS system only. Median overall survival after CNS relapse was 9 months. Five-year isolated CNS relapse rates were 5% in the prophylaxis group and 26% in the group without prophylaxis. These findings suggest that high-dose methotrexate-containing prophylaxis decreases the risk of CNS failure.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/prevenção & controle , Linfoma Difuso de Grandes Células B/prevenção & controle , Metotrexato/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/mortalidade , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Incidência , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Recidiva , Rituximab/administração & dosagem , Vincristina/administração & dosagem
20.
Ann Hematol ; 99(7): 1583-1594, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32506244

RESUMO

Relapsing diffuse large B cell lymphomas (rDLBCL) represent a heterogeneous disease. This heterogeneity should be recognized and reflected, because it can deform the interpretation of clinical trial results. DLBCL patients with the first relapse and without CNS involvement were identified in the Czech Lymphoma Study Group (CLSG) database. Interval-to-therapy (ITT) was defined as the time between the first manifestation of rDLBCL and the start of any treatment. The overall survival (OS) of different ITT cohorts (< 7 vs. 7-21 vs. > 21 days) was compared. In total, 587 rDLBCLs (51.8% males) progressed with a median of 12.8 months (range 1.6 to 152.3) since the initial diagnosis (2000-2017). At the time of relapse, the median age was 67 years (range 22-95). First-line therapy was administered in 99.3% of the patients; CHOP and anti-CD20 were given to 69.2% and 84.7% of the patients, respectively. The salvage immune/chemotherapy was administered in 88.1% of the patients (39.2% platinum-based regimen). The median ITT was 20 days (range 1-851), but 23.2% of patients initiated therapy within 7 days. The 5-year OS was 17.4% (range 10-24.5%) vs. 20.5% (range 13.5-27.4%) vs. 42.2% (range 35.5-48.8%) for ITT < 7 vs. 7-21 vs. > 21 days (p < 0.001). ITT was associated with B symptoms (p 0.004), ECOG (p < 0.001), stage (p 0.002), bulky disease (p 0.005), elevated LDH (p < 0.001), and IPI (p < 0.001). The ITT mirrors the real clinical behavior of rDLBCL. There are patients (ITT < 7 days) with aggressive disease and a poor outcome. Conversely, there are rDLBCLs with ITT ≥ 21 days who survive for a long time.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Ciclofosfamida/uso terapêutico , República Tcheca/epidemiologia , Bases de Dados Factuais , Progressão da Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Prednisona/uso terapêutico , Prognóstico , Recidiva , Estudos Retrospectivos , Rituximab/administração & dosagem , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto Jovem
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