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1.
BMC Infect Dis ; 21(1): 17, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407199

RESUMO

BACKGROUND: Hydroa Vacciniforme-like Lymphoproliferative Disorder (HV-LPD) is the name given to a group of Epstein-Barr virus (EBV)-associated diseases. It resembles hydroa vacciniforme (HV), the rarest form of photosensitivity, and is a T-cell disorder associated with an Epstein-Barr virus infection. The majority of diagnosed cases occur in East Asia and South America. It is rare in the United States and Europe. Multiple studies have revealed the clinical manifestation of an enlarged liver, but no gold standard such as pathology has yet supported this as a clinical sign of HV-LPD. CASE PRESENTATION: Here, we report a case of a 34-year-old Asian female with definite liver invasion. The patient had complained of a recurring facial rash for many years. The patient was admitted to the hospital because of an enlarged liver. After hospitalization, she was given an EB virus nucleic acid test. The EB virus nucleic acid test was positive, and pathological examination suggested that HV-LPD had invaded the skin, bone marrow, and liver. After being given antiviral treatment, the patient's symptoms were mitigated. CONCLUSIONS: Our case confirms the liver damage was caused by HV-LPD and the effectiveness of antiviral treatment.


Assuntos
Medula Óssea/patologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Hidroa Vaciniforme/complicações , Hidroa Vaciniforme/diagnóstico , Fígado/patologia , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/diagnóstico , Adulto , Antivirais/uso terapêutico , Pequim , Medula Óssea/virologia , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Exantema/complicações , Exantema/tratamento farmacológico , Feminino , Hepatomegalia/tratamento farmacológico , Hepatomegalia/virologia , Humanos , Hidroa Vaciniforme/tratamento farmacológico , Hidroa Vaciniforme/patologia , Fígado/virologia , Linfoma de Células T/complicações , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/virologia , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/patologia , Pele/patologia , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(42): e22629, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080699

RESUMO

RATIONALE: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma, which was first defined as a clinical entity in 1991 as a cytotoxic T-cell lymphoma preferentially infiltrating subcutaneous tissue. Herein, we report 2 patients of SPTCL who are a pair of twin brothers. PATIENT CONCERNS: The disease afflicted the monozygotic twin brothers at different time with an interval period of 5 years. The older twin brother had disease onset at 27 years of age. In June 2012, he developed prolonged fever accompanied by subcutaneous nodules in the left upper arm and left chest due to unknown origin. The younger twin brother had disease onset at 32 years of age. In June 2017, the younger brother presented with repeated high fever for more than 10 days, accompanied by head distension. DIAGNOSIS: On August 7, 2012, skin biopsy was performed on the lesion of left upper arm of the older twin brother, and then, a diagnosis of subcutaneous panniculitis-like T cell lymphoma (SPTCL) was made. On June 19, 2017, the younger twin brother underwent whole-body fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for diagnosis. Soon afterwards, abdominal subcutaneous nodule resection and biopsy was performed on June 28, 2018, and the specimen was diagnosed as SPTCL. INTERVENTIONS: For the older brother, a total of 14 systemic chemotherapy sessions were performed from August 16, 2012, to September 21, 2014. For the younger brother, a total of 9 systemic chemotherapy sessions were performed from July 14, 2017, to March 8, 2018, then he was switched to oral chemotherapy with chidamide twice a week for 6 months. OUTCOMES: The older twin brother died in March 2015, the younger brother has recovered well and is no longer receiving any treatment LESSONS:: To the best of our knowledge, twin brothers both having this disease has never been previously reported. Moreover, some of the involved areas are also extremely rare detected by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography at initial stage. It is beneficial to people to gain some new understanding for SPTCL by this special case and some extremely unusual involved sites in the younger twin brother.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Fluordesoxiglucose F18 , Linfoma de Células T/diagnóstico por imagem , Paniculite/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Humanos , Linfoma de Células T/tratamento farmacológico , Masculino , Paniculite/tratamento farmacológico , Gêmeos Monozigóticos
3.
Medicine (Baltimore) ; 99(44): e22490, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126303

RESUMO

RATIONALE: ALL is the most common form of leukemia (75% to 80%), it is characterized by clonal expansion of the lymphoid blasts in bone marrow, blood, and other tissues, which can be divided into T lineage and B lineage. Although relapse of acute leukemia is common, a change of immunophenotype at relapse only occurs rarely. Some of these cases have been labeled "lineage switch". PATIENT CONCERNS: A 31-year-old man had multiple lymph nodes in the neck, and the lymph nodes on the right side adhered to the surrounding tissues. His lymphocytes ratio in blood was up to 86.3%. Flow cytometry of the bone marrow aspirate showed positive results for CD2, CD5, CD7, cCD3, TDT, CD4, CD8, and CD10, negative results for CD34, CD117, CD33, HLA-DR, CD19, and CD20. Twenty six months later, the patient felt pain in the neck and shoulder after touching. His lymphocytes of blood were 109.9×109 /L. 43 fusion genes and positive BCR/ABL was detected. Flow cytometry of the bone marrow aspirate showed pro B lymphocytes accounted for 85.54%, and positive expression of CD38, CD10, CD34, CD33, TDT, CD9, and HLA-DR. Moreover, the RT-PCR data showed the patient expressed high level of T cell and B cell development transcription factors. DIAGNOSES: Upon examination, the patient was initially diagnosed with T-lineage pro cell ALL. BM morphologic analysis presented complete remission (CR) after systemic chemotherapy. Twenty six months later, we discovered the patient was diagnosed with B-lineage acute lymphocytic leukemia. INTERVENTIONS: Systemic chemotherapy is first given when a patient was diagnosed with T-cell acute lymphoblastic leukemia. After the patient happened linage switch, we adjusted the treatment plan, and the patient was complete remission after 1 course of treatment. OUTCOMES: Our case provides information of lineage switch from T-ALL to B-ALL in this report, which is never seen in our knowledge. LESSONS: This lineage switch from T-ALL to B-ALL is never reported beforemoreover, the RT-PCR data showed the patient expressed high level of T cell and B cell development transcription factors. Its early recognition can let doctor provides appropriate therapy to patient.


Assuntos
Leucemia Aguda Bifenotípica/sangue , Linfoma de Células B/sangue , Linfoma de Células T/sangue , Doença Aguda , Adulto , Linfócitos B , Linhagem da Célula , Humanos , Leucemia Aguda Bifenotípica/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Masculino , Linfócitos T
4.
Anticancer Res ; 40(9): 4921-4928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878780

RESUMO

BACKGROUND/AIM: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. MATERIALS AND METHODS: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. RESULTS: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 µM). Thioridazine was the most potent among the three phenothiazines. CONCLUSION: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.


Assuntos
Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Fenotiazinas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Camundongos , Estrutura Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/química , Fenotiazinas/síntese química , Fenotiazinas/química
5.
Zhonghua Bing Li Xue Za Zhi ; 49(10): 1021-1026, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-32992416

RESUMO

Objective: To investigate the clinicopathological characteristics of the T cell lymphomas with CD20 expression, and to better understand this rare entity. Methods: Two-hundred cases of T-cell lymphoma diagnosed in the Department of Pathology of the Affiliated Hospital of Qingdao University from November 2016 to February 2020 were examined, and 5 cases of CD20-positive T-cell lymphomas were identified and included. Combined with clinical data and review of the literature, the clinicopathological characteristics of the disease were analyzed. Results: The five patients were all male, and had an average age of 56 years (range, 47 to 64 years). There were 2 cases of monomorphic epitheliotropic intestinal T-cell lymphoma, 2 cases of mycosis fungoides (1 case was plaque stage and the other was tumor stage) and 1 case of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Immunohistochemistry showed that all 5 cases expressed multiple T cell markers (CD3/CD4/CD5/CD7/CD8) and only one of B cell markers (CD20). Three of the 5 cases were negative for CD20 at the first diagnosis, while CD20 was diffusely positive on the second biopsy from the recurrence or progression of the disease, without expression of CD79a or PAX5. Epstein-Barr encoding region (EBER) in situ hybridization was negative in all 5 cases. T-cell receptor gene analysis showed monoclonal rearrangement of ß or/and δ chains;Ig rearrangements were all polyclonal. None of the five patients were treated with rituximab, and 4 patients survived with disease and 1 patient survived without disease at the end of follow-up. Among them, the patient with mycosis fungoides at the cancerous stage has progressed rapidly and had poor quality of life. Conclusions: CD20-positive T-cell lymphoma is extremely rare. Its prognosis is closely related to the type of T-cell lymphoma, clinical stage and initial therapeutic effect. However, the expression of CD20 indicates the recurrence or progression of the disease, and the prognosis is relatively poor. When CD3 expression is absent in T-cell lymphoma, it is easy to be misdiagnosed as B-cell lymphoma. The combination of multiple immunohistochemical antibodies and molecular detection can improve the accuracy of diagnosis.


Assuntos
Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/genética , Micose Fungoide , Neoplasias Cutâneas , Antígenos CD20 , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
7.
Nat Commun ; 11(1): 2860, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503978

RESUMO

The MYC oncogene drives T- and B- lymphoid malignancies, including Burkitt's lymphoma (BL) and Acute Lymphoblastic Leukemia (ALL). Here, we demonstrate a systemic reduction in natural killer (NK) cell numbers in SRα-tTA/Tet-O-MYCON mice bearing MYC-driven T-lymphomas. Residual mNK cells in spleens of MYCON T-lymphoma-bearing mice exhibit perturbations in the terminal NK effector differentiation pathway. Lymphoma-intrinsic MYC arrests NK maturation by transcriptionally repressing STAT1/2 and secretion of Type I Interferons (IFNs). Treating T-lymphoma-bearing mice with Type I IFN improves survival by rescuing NK cell maturation. Adoptive transfer of mature NK cells is sufficient to delay both T-lymphoma growth and recurrence post MYC inactivation. In MYC-driven BL patients, low expression of both STAT1 and STAT2 correlates significantly with the absence of activated NK cells and predicts unfavorable clinical outcomes. Our studies thus provide a rationale for developing NK cell-based therapies to effectively treat MYC-driven lymphomas in the future.


Assuntos
Linfoma de Burkitt/imunologia , Células Matadoras Naturais/imunologia , Linfoma de Células T/imunologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transferência Adotiva , Animais , Linfoma de Burkitt/mortalidade , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Vigilância Imunológica/genética , Interferon Tipo I/farmacologia , Interferon Tipo I/uso terapêutico , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/transplante , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/genética , Linfoma de Células T/patologia , Masculino , Camundongos , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-myc/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia
8.
Gan To Kagaku Ryoho ; 47(1): 95-97, 2020 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-32381871

RESUMO

Pralatrexate(PDX)has been approved for the treatment of relapsed/refractory peripheral T-cell lymphoma(PTCL), including angioimmunoblastic T-cell lymphoma(AITL). Oral mucositis is the most common and severe adverse effect of PDX that often leads to dose reduction or omission. Herein, we report a 65-year-old man with AITL, who received PDX treatment after a second relapse. This drug was effective; however, the adverse effects, such as oral mucositis, were severe. Therefore, leucovorin(LV)was administered to prevent the adverse effect, resulting in continuation of the PDX treatment for 8 months. LV administration minimizes adverse effects for patients receiving high-dose methotrexate. However, the optimal dose and schedule of LV in PDX treatment has not yet been established. In the future, clinical trials on the use of LV for PDX-induced oral mucositis are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Idoso , Aminopterina/análogos & derivados , Antagonistas do Ácido Fólico , Humanos , Leucovorina , Masculino , Recidiva Local de Neoplasia
9.
Sci Rep ; 10(1): 6721, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317694

RESUMO

Patients diagnosed with T-cell leukemias and T-cell lymphomas (TCLs) still have a poor prognosis and an inadequate response to current therapies, highlighting the need for targeted treatments. We have analyzed the potential therapeutic value of the farnesyltransferase inhibitor, tipifarnib, in 25 TCL cell lines through the identification of genomic and/or immunohistochemical markers of tipifarnib sensitivity. More than half of the cell lines (60%) were considered to be sensitive. Tipifarnib reduced cell viability in these T-cell leukemia and TCL cell lines, induced apoptosis and modified the cell cycle. A mutational study showed TP53, NOTCH1 and DNMT3 to be mutated in 84.6%, 69.2% and 30.0% of sensitive cell lines, and in 62.5%, 0% and 0% of resistant cell lines, respectively. An immunohistochemistry study showed that p-ERK and RelB were associated as potential biomarkers of tipifarnib sensitivity and resistance, respectively. Data from RNA-seq show that tipifarnib at IC50 after 72 h downregulated a great variety of pathways, including those controlling cell cycle, metabolism, and ribosomal and mitochondrial activity. This study establishes tipifarnib as a potential therapeutic option in T-cell leukemia and TCL. The mutational state of NOTCH1, p-ERK and RelB could serve as potential biomarkers of tipifarnib sensitivity and resistance.


Assuntos
Biomarcadores Tumorais/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Quinolonas/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/genética , Linfoma de Células T/patologia , Mutação/genética , Fenótipo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Quinolonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
10.
Folia Histochem Cytobiol ; 58(1): 46-53, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176312

RESUMO

INTRODUCTION: Canine lymphoma remains one of the most chemotherapy-responsive neoplasia in dogs. Many factors affect the prognosis in dogs treated for lymphoma, but indications for a specific treatment regimen in individual animals with lymphoma are poorly defined. Topoisomerase IIα (TOPIIα) is a key enzyme in DNA replication and a molecular target for TOPIIα inhibitors, including anthracyclines. The aim of this study was to determine the expression of TOPIIα in canine malignant lymphomas. The relationship between TOPIIα expression in canine lymphomas and potential sensitivity of neoplastic cells to anthracycline-based chemotherapy is discussed. MATERIALS AND METHOD: Samples of formalin-fixed paraffin-embedded lymph nodes from 47 dogs with different subtypes of non-Hodgkin's (34 B-cell and 13 T-cell) lymphoma were immunohistochemically labeled with anti-TOPIIα. The number of positive cells and the intensity of the reaction were taken into account in order to assess TOPIIα expression. RESULTS: TOPIIα expression was evident in all cases, although differences in the number of positive cells and intensity of the reaction were demonstrated between B-cell and T-cell lymphoma groups as well as within individual groups. Based on the established scoring system, in the B-cell lymphoma group statistically higher expression of TOPIIα was found compared to the T-cell lymphoma group (P = 0.006). In B-cell lymphoma group moderate (41.18%) and strong (32.35%) TOPIIα expression predominated, whereas among T-cell lymphoma group the majority were cases with a weak (46.15%) TOPIIα expression. CONCLUSION: These preliminary results indicate that further studies are needed to determine the prognostic value of TOPIIα expression with regard to the sensitivity of canine B-cell lymphomas to anthracycline-based chemotherapy regimen. Nevertheless, this study indicates the possibility of choosing the appropriate treatment of canine lymphoma based on TOPIIa expression.


Assuntos
Biomarcadores Tumorais/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Doenças do Cão/metabolismo , Linfoma de Células B/metabolismo , Linfoma de Células T/metabolismo , Animais , Anticorpos Monoclonais/imunologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/imunologia , DNA Topoisomerases Tipo II/imunologia , Doenças do Cão/tratamento farmacológico , Cães , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma de Células B/veterinária , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/veterinária , Masculino , Inibidores da Topoisomerase II/uso terapêutico
11.
Cancer Res ; 80(9): 1875-1884, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32107212

RESUMO

Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2-null background succumbed to AITL-like T-cell lymphomas due to deregulated T-cell receptor (TCR) signaling. Using these mice to investigate therapeutics for AITL, we found that dasatinib, a multikinase inhibitor prolonged their survival through inhibition of hyperactivated TCR signaling. A phase I clinical trial study of dasatinib monotherapy in 5 patients with relapsed/refractory AITL was performed. Dasatinib was started at a dose of 100 mg/body once a day and continued until days 10-78 (median day 58). All the evaluable patients achieved partial responses. Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment. SIGNIFICANCE: Deregulated T-cell receptor signaling is a critical molecular event in angioimmunoblastic T-cell lymphoma and can be targeted with dasatinib.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Ligação a DNA/genética , Dasatinibe/uso terapêutico , Linfadenopatia Imunoblástica/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Proteínas Proto-Oncogênicas/genética , Receptores de Antígenos de Linfócitos T/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/genética , Idoso , Animais , Antineoplásicos/administração & dosagem , Dasatinibe/administração & dosagem , Modelos Animais de Doenças , Esquema de Medicação , Feminino , Humanos , Linfadenopatia Imunoblástica/sangue , Linfadenopatia Imunoblástica/genética , Interferon gama/sangue , Interleucinas/sangue , Linfoma de Células T/sangue , Linfoma de Células T/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-vav/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/sangue
13.
Clin Nucl Med ; 45(2): e69-e71, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31833924

RESUMO

A 30-year-old woman presented with persistent fever and elevated lactate dehydrogenase levels without skin rash. F-FDG PET/CT revealed FDG uptake in subcutaneous tissues in the forearm, buttocks, and lower limbs, whereas the trunk was unaffected. She was diagnosed with subcutaneous panniculitis-like T-cell lymphoma based on a PET/CT-guided subcutaneous tissue biopsy from the thigh. Although conventional cytotoxic agent-based chemotherapies failed to achieve disease remission, subsequent cyclosporine A treatment promptly resolved the fever and laboratory abnormalities. Remarkably, abnormal FDG uptake disappeared entirely on follow-up PET/CT, demonstrating its utility in the evaluations of responses to emerging cyclosporine A-based treatments in subcutaneous panniculitis-like T-cell lymphoma.


Assuntos
Ciclosporina/farmacologia , Fluordesoxiglucose F18 , Linfoma de Células T/diagnóstico por imagem , Linfoma de Células T/tratamento farmacológico , Paniculite/diagnóstico por imagem , Paniculite/tratamento farmacológico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Ciclosporina/uso terapêutico , Feminino , Humanos , Linfoma de Células T/patologia , Paniculite/patologia , Resultado do Tratamento
15.
Am J Clin Oncol ; 43(4): 257-262, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31764026

RESUMO

OBJECTIVES: Natural killer/T-cell lymphoma (NKTCL) is aggressive, and carries a poor prognosis worldwide. This retrospective study aimed to evaluate the clinical efficacy and safety of the LVD regimen (L-asparaginase, vincristine, and dexamethasone) combined with intensity-modulated radiation therapy (IMRT) for the treatment of early-stage nasal NKTCL in a Chinese population. METHODS: The clinical data were collected from patients treated between March 2010 and January 2017. Patients received LVD chemotherapy combined with IMRT, and were followed for 30 to 90 months. All received radiotherapy at the end of the first/second cycle of chemotherapy. The survival curves were generated by the Kaplan-Meier method. RESULTS: Among 94 patients who received 2 to 6 cycles (mean, 4 cycles) of treatments, 56 and 25 achieved complete and partial remission, respectively; 2 and 11 experienced stable disease and progressive disease. The overall objective response was 86.2%. Patients with elevated lactate dehydrogenase and skin invasion had a lower objective response rate. The progression-free survival rates at 1, 3, and 5 years were 90.3%, 73.5%, and 71.3%; the corresponding overall survival rates were 91.4%, 74.3%, and 74.3%. The main adverse events were myelosuppression (63.8% grades I to II, 12.8% grade III), gastrointestinal symptoms (63.8% grades I to II), hepatic lesion (55.3% grades I to II), hypoproteinemia (46.8% grades I to II), skin allergies (77.7% grades I to II, 3.2% grade III), and oral mucosal lesions (44.7% grades I to II, 33% grade III). No severe pancreatitis, anaphylaxis, or toxicity-related death was observed. CONCLUSION: In patients with early-stage nasal NKTCL, our LVD-IMRT regimen produced excellent, durable therapeutic benefit in most patients, with acceptable toxicity and no acute mortality.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Dexametasona/administração & dosagem , Células Matadoras Naturais , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/radioterapia , Neoplasias Nasais/tratamento farmacológico , Neoplasias Nasais/radioterapia , Radioterapia de Intensidade Modulada , Vincristina/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/efeitos adversos , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/efeitos adversos , Adulto Jovem
16.
Pediatr Blood Cancer ; 67(1): e28021, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571395

RESUMO

Hypersensitivity to pegaspargase is associated with inferior survival in pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. In the past year, drug-supply shortages have led to the lack of an available alternative to pegaspargase. Rather than omit asparaginase from the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma patients with hypersensitivity to pegaspargase, we continued pegaspargase treatments for nine pediatric patients, utilizing a rapid desensitization protocol. There were no adverse events related to the pegaspargase during desensitization, and all patients who were checked had asparaginase serum levels above the threshold of 0.1 IU/mL at 7 to 14 days after pegaspargase therapy.


Assuntos
Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Dessensibilização Imunológica/métodos , Linfoma de Células T/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Humanos , Linfoma de Células T/imunologia , Linfoma de Células T/patologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico
17.
Ann Pharmacother ; 54(4): 371-379, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31648540

RESUMO

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, dosing, and administration of mogamulizumab for the treatment of T-cell lymphomas. Data Sources: A literature search of PubMed (1966 to September 2019) was conducted using the keywords mogamulizumab, KW-0761, and lymphoma. Data were also obtained from package inserts and meeting abstracts. Study Selection and Data Extraction: All relevant published articles, package inserts, and unpublished meeting abstracts on mogamulizumab for the treatment of T-cell lymphomas were reviewed. Data Synthesis: Mogamulizumab is an anti-CC chemokine receptor 4 (CCR4) monoclonal antibody that has demonstrated activity in various T-cell lymphomas. It was approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) who have been treated with at least 1 prior line of therapy. Mogamulizumab demonstrated significant improvement in progression-free survival compared with vorinostat in patients with relapsed or refractory MF or SS. Serious adverse events associated with mogamulizumab include infusion-related reactions, cutaneous drug eruption, and autoimmune complications. Mogamulizumab administration in the preallogeneic hematopoietic stem cell transplant setting can increase the risk for severe posttransplant graft-versus-host disease. Relevance to Patient Care and Clinical Practice: Mogamulizumab is a first-in-class CCR4 inhibitor, providing a new option in the treatment of relapsed or refractory cutaneous T-cell lymphomas. Although not currently FDA approved for this indication, mogamulizumab may have some utility for the treatment of relapsed adult T-cell leukemia/lymphoma. Conclusion: The recent approval of mogamulizumab represents an important addition to the armamentarium of pharmacotherapies for T-cell lymphomas.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Receptores CCR4/antagonistas & inibidores , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Erupção por Droga/etiologia , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Linfoma de Células T/complicações , Linfoma de Células T/patologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Pessoa de Meia-Idade , Receptores CCR4/imunologia , Recidiva , Neoplasias Cutâneas/tratamento farmacológico
18.
Br J Haematol ; 188(2): 295-308, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31452195

RESUMO

Ixazomib activity and transcriptomic analyses previously established in T cell (TCL) and Hodgkin (HL) lymphoma models predicted synergistic activity for histone deacetylase (HDAC) inhibitory combination. In this present study, we determined the mechanistic basis for ixazomib combination with the HDAC inhibitor, belinostat, in HL and TCL cells lines (ixazomib-sensitive/resistant clones) and primary tumour cells. In ixazomib-treated TCL and HL cells, transient inhibition followed by full recovery of proteasomal activity observed was accompanied by induction of proteasomal gene expression with NFE2L2 (also termed NRF2) as a prominent upstream regulator. Downregulation of both NFE2L2 and proteasomal gene expression (validated by quantitative real time polymerase chain reaction) occurred with belinostat treatment in Jurkat and L428 cells. In addition, CRISPR/Cas9 mediated knockdown of NFE2L2 in Jurkat cells resulted in a significant decrease in cell viability with ixazomib compared with untreated control cells. Using transcriptomic and proteasomal activity evaluation of ixazomib, belinostat, or ixazomib + belinostat treated cells, we observed that NFE2L2, proteasome gene expression and functional recovery were abrogated by ixazomib + belinostat combination, resulting in synergistic drug activity in ixazomib-sensitive and -resistant cell lines and primary cells. Altogether, these results suggest that the synergistic activity of ixazomib + belinostat is mediated via inhibition NFE2L2-dependent proteasomal recovery and extended proteasomal inhibition culminating in increased cell death.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Doença de Hodgkin/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Fator 2 Relacionado a NF-E2/genética , Apoptose/efeitos dos fármacos , Compostos de Boro/administração & dosagem , Compostos de Boro/farmacologia , Linhagem Celular Tumoral , Regulação para Baixo , Sinergismo Farmacológico , Glicina/administração & dosagem , Glicina/análogos & derivados , Glicina/farmacologia , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Ácidos Hidroxâmicos/farmacologia , Células Jurkat , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Fator 2 Relacionado a NF-E2/biossíntese , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia
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