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1.
Medicine (Baltimore) ; 98(45): e17872, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702654

RESUMO

RATIONALE: Ewing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) is a rare type of soft tissue sarcomas (STS), especially in infants, with poor prognosis. It is a so-called "small round cell" sarcoma, and has many features of Ewing sarcoma, but lacks rearrangements in EWSR1. The diagnosis and treatment of this kind of STS remains challenging. BCOR genetic abnormalities have been found in some Ewing-like sarcomas. PATIENT CONCERNS: This report presents an ELS case of a female infant, who was 2 months old when initially diagnosed, with the clinical stage of IIIA (G2T2N0M0). Histologic findings revealed an undifferentiated neoplasm composed of small round tumor cells with round, open chromatic nuclei, and scant cytoplasm in a sheet growth pattern. Fluorescence in situ hybridization (FISH) analysis showed absence of EWSR1 and ETV6 gene rearrangement. Molecular genetic testing found no established variants of clinical significance but variants of unknown significance in APC, KMT2D, and MSH6 were detected. Immunostaining revealed that the tumor cells were positive for TLE1 and BCOR, and negative for cytokeratin (AE1/AE3), Desmin, CD45, S100, CD31, HMB45, and SATB2. INI-1 was retained. DIAGNOSIS: Ewing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) INTERVENTIONS:: After initial diagnosis, the patient received 4 cycles of combination chemotherapy for 2 months. Radical amputation of left upper extremity was performed 3 months after diagnosis. Postoperative chemotherapy was continued for 6 cycles. OUTCOMES: The patient died of intracranial metastasis with hemorrhage in 13 months after initial diagnosis, 5 months after the last cycle of chemotherapy. LESSONS: ELS in infancy is extremely rare and has a poorer prognosis than Ewing sarcoma or infantile fibrosarcoma. APC and MSH6 variation might be related with the disease progression and predict a poorer prognosis. This rare case promotes better understanding of the disease and suggests a promising role for the combination chemotherapy regimen in treating infantile ELS. Importantly, it brings to light the possibility of intracranial metastasis, which requires proactive screening for timely detection.


Assuntos
Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Evolução Fatal , Feminino , Antebraço/diagnóstico por imagem , Humanos , Lactente , Sarcoma/diagnóstico por imagem , Sarcoma/tratamento farmacológico , Sarcoma/genética , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/genética , Ultrassonografia Doppler em Cores , Vincristina/uso terapêutico
2.
Rinsho Ketsueki ; 60(9): 1193-1198, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597843

RESUMO

In 2018 the practical guidelines for hematological malignancies, edited by Japanese Society of Hematology, underwent major revision for the first time in five years. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard treatment for diffuse large B-cell lymphoma (DLBCL) in line with the prior 2013 guidelines. R-CHOP has been considered as the standard treatment for DLBCL since early 2000s, when a 20% improvement in survival was observed when adding rituximab to CHOP. Following this, several clinical trials were conducted, but most attempts to exceed R-CHOP have failed. Moreover, this evidence has raised further research questions. In this report, the current evidence and the problems associated with DLBCL treatments have been reviewed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Prednisona/uso terapêutico , Rituximab , Resultado do Tratamento , Vincristina/uso terapêutico
3.
Cancer Immunol Immunother ; 68(12): 1949-1958, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637474

RESUMO

Diffusing alpha-emitters radiation therapy (DaRT) is the only known method for treating solid tumors with highly destructive alpha radiation. More importantly, as a monotherapy, DaRT has been shown to induce a systemic antitumor immune response following tumor ablation. Here, immunomodulatory strategies to boost the antitumor immune response induced by DaRT, and the response specificity, were investigated in the colon cancer CT26 mouse model. Local treatment prior to DaRT, with the TLR3 agonist poly I:C, was sufficient to inhibit tumor growth relative to poly I:C or DaRT alone. DaRT used in combination with the TLR9 agonist CpG, or with the TLR1/2 agonist XS15 retarded tumor growth and increased tumor-rejection rates, compared to DaRT alone, curing 41% and 20% of the mice, respectively. DaRT in combination with CpG, the Treg inhibitor cyclophosphamide, and the MDSC inhibitor sildenafil, cured 51% of the animals, compared to only 6% and 0% cure when immunomodulation or DaRT was used alone, respectively. Challenge and Winn assays revealed that these high cure rates involved a specific immunological memory against CT26 antigens. We suggest that DaRT acts in synergy with immunomodulation to induce a specific and systemic antitumor immune response. This strategy may serve as a safe and efficient method not only for tumor ablation, but also for in situ vaccination of cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Neoplasias do Colo/terapia , Ciclofosfamida/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Neoplasias Experimentais/terapia , Partículas alfa , Animais , Antígenos de Neoplasias/imunologia , Células Cultivadas , Feminino , Humanos , Imunidade , Memória Imunológica , Camundongos , Camundongos Endogâmicos BALB C , Poli I-C/administração & dosagem , Indução de Remissão
4.
Zhonghua Nei Ke Za Zhi ; 58(10): 758-762, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31594174

RESUMO

Objective: To investigate the clinical characteristics of polyarteritis nodosa (PAN) patients with renal involvement. Methods: PAN patients admitted to the department of rheumatology, department of pediatrics, department of nephrology, general internal medicine department and department of vascular surgery at Peking Union Medical College Hospital from June 2012 to August 2018 were enrolled in this study and were divided into two groups according to renal involvement or not. The clinical characteristics were analyzed. Results: A total of 94 PAN patients were finally enrolled and 57 (60.64%) presented kidney manifestation. The mean age of onset was (37.76±17.40) years old and the interval from onset to diagnosis was 10 (0 to 240) months. Forty patients were misdiagnosed once or more times. In patients with renal involvement, 9 cases suffered from renal ischemia or infarction, 31 with microscopic haematuria, 26 with proteinuria, renal artery or its branch involved in 17 cases, renal vein thrombosis in 1 case, 4 cases with pyeloureterectasis, one case with renal fascia thickening, 33 cases with impaired renal function (serum creatinine>84 µmol/L) including creatinine>140 µmol/L in 10 patients. Renal artery branch stenosis was the most common presentation [9 cases (52.94%)] of renal vascular involvement, other abnormalities including nodular dilatation [4 cases (23.53%)], occlusion [3 cases (17.65%)]. There were significant differences (P<0.05) in the PAN patients with and without renal involvement in the following: age of onset [(33.72±16.13) years vs. (43.97±17.66) years, t(2)=2.901, P=0.005], weight loss(≥4kg since PAN onset) [25(43.86%) vs. 7(18.92%), χ(2)=6.216, P=0.013], elevation of diastolic blood pressure [22(38.60%) vs. 7(18.92%), χ(2)=4.072, P=0.044], acromegaly gangrene [18(31.58%) vs. 21(56.76%), χ(2)=5.859, P=0.015], and gastrointestinal artery involvement [20(35.09%) vs. 6(1.22%), χ(2)=3.993, P=0.046]. Laboratory parameters and the application of glucocorticoid and cyclophosphamide therapies were similar in two groups (all P>0.05). Conclusion: Young PAN patients are more likely to be associated with renal involvement, especially gastrointestinal arteries.


Assuntos
Arterite/diagnóstico , Nefropatias/etiologia , Rim/fisiopatologia , Poliarterite Nodosa/diagnóstico , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Gastroenteropatias , Glomerulonefrite/diagnóstico , Glucocorticoides/uso terapêutico , Humanos , Infarto , Nefropatias/fisiopatologia , Pessoa de Meia-Idade , Poliarterite Nodosa/complicações , Poliarterite Nodosa/tratamento farmacológico , Adulto Jovem
7.
Internist (Berl) ; 60(10): 1106-1110, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31435719

RESUMO

We describe a patient with ANCA (antineutrophil cytoplasmic antibodies) associated vasculitis and acute-on-chronic renal failure. He had initially presented with severe pulmonary hemorrhage and anuric renal failure and improved rapidly with immunosuppressive therapy. Repeat renal biopsy revealed candida interstitial nephritis. Candida was also detected in bronchoalveolar lavage. Kidney function improved with long-term antifungal therapy. This report adds induction therapy for ANCA vasculitis to the conditions where invasive candidal infections including nephritis need to be considered.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Antifúngicos/uso terapêutico , Candida/isolamento & purificação , Falência Renal Crônica/diagnóstico , Doença Aguda , Lesão Renal Aguda , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/microbiologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Biópsia , Candida/classificação , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/microbiologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Resultado do Tratamento
8.
Adv Clin Exp Med ; 28(9): 1223-1228, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430069

RESUMO

BACKGROUND: Unmanipulated haploidentical stem cell transplantation (haploSCT) with post-transplant cyclophosphamide is an option for patients with advanced hematologic malignancies. It offers a platform both for non-major histocompatibility complex-restricted alloimmunity due to killer-like immunoglobulin receptor (KIR)-mediated mechanisms of natural killer lymphocyte regulation and for classical T-cell mediated antileukemic effects. OBJECTIVES: The devastating long-term sequelae after total body irradiation (TBI) in children are encouraging omission of irradiation techniques in pediatric stem cell transplantations (SCT). MATERIAL AND METHODS: Five children, 4 with acute leukemia and 1 with hemophagocytic lymphohistiocytosis, aged from 1 to 10 years, underwent haploSCT with post-transplantation cyclophosphamide. In all children, the conditioning regimen consisted of chemotherapy without TBI. The graft material was bone marrow (BM) in 4 cases and peripheral blood stem cells in 1 case. Three out of 5 leukemic patients showed better KIR haplotype associated with augmented alloreactivity. RESULTS: Engraftment with complete donor chimerism was achieved in 4 patients, and 1 recipient died before leukocyte recovery. Three patients developed skin acute graft-versus-host-disease (aGvHD), 1 gut aGvHD and 1 liver aGvHD. In 2 recipients, chronic graft-versus-host-disease (cGvHD) was observed (1 limited and 1 extensive). The 4 engrafted patients were alive and in complete remission 3, 9, 32, and 36 months after transplantation. A T-cell count of 200 cells/uL was reached 90 days after haploSCT in all patients. CONCLUSIONS: HaploSCT with TBI-free protocols can be a viable option for heavily pretreated patients with advanced malignancies.


Assuntos
Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Condicionamento Pré-Transplante , Irradiação Corporal Total
9.
An Bras Dermatol ; 94(3): 337-340, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365665

RESUMO

Necrobiotic xanthogranuloma is a rare chronic condition, belonging to the group C non-Langerhans cell histiocytoses, which is relevant due to the possibility of extracutaneous involvement and association with systemic diseases, particularly hematologic malignancies. The case reported here was only diagnosed after nine years of evolution and was associated with plasma cell dyscrasia. After treatment with cyclophosphamide, dexamethasone, and thalidomide, there was a reduction of cutaneous lesions and serum levels of monoclonal protein.


Assuntos
Xantogranuloma Necrobiótico/tratamento farmacológico , Mieloma Múltiplo Latente/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Xantogranuloma Necrobiótico/complicações , Xantogranuloma Necrobiótico/patologia , Mieloma Múltiplo Latente/complicações , Mieloma Múltiplo Latente/patologia , Talidomida/uso terapêutico , Resultado do Tratamento
10.
Medicine (Baltimore) ; 98(31): e16688, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374054

RESUMO

The objectives of this study were to analyze the clinical features of patients with bone involved lymphoma and identify the prognostic factors and to explore the optimized treatment strategy for bone involved lymphoma.A total of 1948 patients with lymphoma in our cancer center from September 2006 to October 2017 were retrospectively evaluated. Among these, 109 patients with skeletal involvement in lymphoma were enrolled. According to the pathologic subtypes, the patients were divided into 3 subgroups: classic Hodgkin lymphoma (cHL), B-cell non-Hodgkin lymphoma (B-NHL), and T-cell non-Hodgkin lymphoma (T-NHL). The clinical characteristics and overall survival (OS) of 3 groups of patients were reviewed, and the prognostic factors were analyzed.There were 9 (3 unifocal, 6 multifocal) patients with primary bone lymphoma. The 5-year OS of cHL, B-NHL, and T-NHL patients was 88.24%, 54.09%, and 61.58%, respectively. Advanced stage, elevated lactate dehydrogenase (LDH), age above 60, high International Prognostic Index score, and treatment without radiotherapy for the bone involved were significant poor prognostic factors for OS of all patients in univariate analysis. There was a trend toward better OS not only in limited-stage but also in advanced-stage patients with radiotherapy for the bone involved compared with the patients without radiotherapy. Elevated LDH level and age above 60 were the independent unfavorable prognostic factor in multivariate analysis.Elevated LDH level and age above 60 predict the poor prognosis of patients with bone involvement. The potential for long-term survival suggests that additional consolidative radiotherapy for the site of skeleton involvement may have a better chance of long-term success.


Assuntos
Neoplasias Ósseas/radioterapia , Doença de Hodgkin/radioterapia , Linfoma de Células B/radioterapia , Linfoma de Células T/radioterapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Estudos de Casos e Controles , Terapia Combinada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Estimativa de Kaplan-Meier , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/mortalidade , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Vincristina/uso terapêutico
11.
Rev Med Chil ; 147(3): 275-280, 2019 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-31344163

RESUMO

BACKGROUND: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. AIM: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. PATIENTS AND METHODS: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. RESULTS: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. CONCLUSIONS: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.


Assuntos
Macroglobulinemia de Waldenstrom/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Medula Óssea/patologia , Chile/epidemiologia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/mortalidade
12.
Rev Med Chil ; 147(3): 390-394, 2019 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-31344179

RESUMO

Goodpasture Syndrome is described as a single episode disease entity. It is diagnosed with the demonstration of antiglomerular basement (anti-GBM) antibodies in plasma or renal tissue. Although the recurrence of anti-GBM disease is rare, it has been reported in up to 3% of cases. Recurrence with negative anti-GBM antibodies in plasma is even less frequent We report a 63 years old male in whom anti-GBM disease recurred without detectable anti-GBM antibodies in plasma, despite having positive antibodies at the onset.


Assuntos
Doença Antimembrana Basal Glomerular/patologia , Autoanticorpos/análise , Antibacterianos/uso terapêutico , Doença Antimembrana Basal Glomerular/diagnóstico por imagem , Doença Antimembrana Basal Glomerular/tratamento farmacológico , Biópsia , Ciclofosfamida/uso terapêutico , Imunofluorescência , Humanos , Nefropatias/patologia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Recidiva , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
13.
Ann Hematol ; 98(9): 2025-2033, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31312929

RESUMO

Outcomes for patients with non-Hodgkin's lymphoma (NHL) that proves refractory to treatment remain poor. Treatment of such patients is individualized and can include enrolment in a clinical trial of novel agents or use of one of a wide array of drug regimens. Initial treatment with anthracyclines such as doxorubicin limits options at later stages of treatment because of anthracycline-related cumulative cardiotoxicity. The aza-anthracenedione pixantrone was developed to reduce the likelihood of cardiotoxicity without compromising efficacy and is currently conditionally approved for use as monotherapy in patients with multiply-relapsed or refractory aggressive B cell NHL. The use of pixantrone in combination therapy, often to replace doxorubicin or mitoxantrone, has or is currently being investigated in numerous studies in patients with aggressive or indolent NHL and is the focus of this review. These include the R-CPOP regimen (rituximab, cyclophosphamide, pixantrone, vincristine, prednisone) for aggressive NHL in the first-line setting, including a study in elderly patients with limited cardiac function, and for patients with relapsed NHL with prior anthracycline exposure; the PSHAP regimen (pixantrone, cytarabine, prednisone, cisplatin), also in the latter setting; the PREBen/PEBen regimen (pixantrone, bendamustine and etoposide with or without rituximab) as salvage therapy; and pixantrone in combination with fludarabine, dexamethasone, and rituximab (FPD-R) for relapsed indolent NHL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Isoquinolinas/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Mitoxantrona/uso terapêutico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Terapia de Salvação/métodos , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vincristina/uso terapêutico
14.
Zhonghua Nei Ke Za Zhi ; 58(6): 444-448, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31159524

RESUMO

Objective: To assess the efficacy and safety of tocilizumab and cyclophosphamide in patients with Takayasu arteritis (TA). Methods: Twenty-seven TA patients treated with tocilizumab (TCZ group) and 22 treated with cyclophosphamide (CTX group) were enrolled and retrospectively analyzed. The duration of treatment was 6 months. Disease activity and side effects were compared between the two groups. Results: After treatment, the median C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity scores in TCZ group were significantly lower than those in CTX group respectively [ESR 3 mm/1h vs. 8 mm/1h; CRP 0.13 mg/L vs. 1.09 mg/L; National Institutes of Health (NIH) score 0(0,1) vs. 0(1,1); the Indian Takayasu clinical activity score (ITAS 2010) 0(0,2) vs. 2(0,3.5), and the Indian Takayasu activity score with the acute phase response (ITAS-A) 0(0,2) vs. 2.5(0,3.5); all P<0.05]. The daily prednisone doses before treatment and after treatment in TCZ group were significantly lower than those in CTX group [(20.1±15.9) mg/d vs. (39.3±16.7) mg/d;(5.1±4.2)mg/d vs. (12.1±4.6) mg/d,both P<0.05)].The incidence of drug-related side effects in TCZ group was significantly lower than that in CTX group, which was 22.2% vs. 54.5% (P<0.05). Conclusion: Compared with CTX treatment, TCZ treatment for TA with less prednisone has better efficacy and safety.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclofosfamida/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Ciclofosfamida/administração & dosagem , Humanos , Estudos Retrospectivos , Arterite de Takayasu/patologia , Resultado do Tratamento
15.
J Clin Pathol ; 72(9): 630-635, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31189540

RESUMO

AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia. METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS). RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTK high/LYN high) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05). CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Medicina de Precisão/métodos , Receptores de Antígenos de Linfócitos B/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/imunologia , Tomada de Decisão Clínica , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/etnologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prevalência , Receptores de Antígenos de Linfócitos B/imunologia , Sistema de Registros , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
16.
Medicine (Baltimore) ; 98(20): e15706, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096519

RESUMO

RATIONALE: Anti-IgLON5 disease is a complex neurological illness which is characterized by progressive sleep and movement disorders and defined by specific autoantibodies to IgLON5. We here describe the first case of a patient with coexisting anti-IgLON5 as well as anti-γ-aminobutyric acid B (GABAB)-receptor antibodies and predominant clinical features of anti-IgLON5 disease. PATIENT CONCERNS: The patient initially presented with subacute symptoms of severe sleep disorder, gait stability, dysarthria, cognitive impairment, depressive episode and hallucinations. DIAGNOSES: The patient was diagnosed with autoimmune encephalitis, based on clinical features and positive anti-IgLON5 antibodies in serum as well as in cerebrospinal fluid and anti-GABAB-receptor antibodies in serum only. INTERVENTIONS: Initially, the patient was treated with high dosages of methylprednisolone and subsequently with plasmapheresis. Due to the lack of clinical improvement immunosuppressive treatment with intravenous cyclophosphamide was initiated. OUTCOMES: Following the first year of cyclophosphamide treatment, neurological examination revealed an improvement in gait instability, visual and acoustic hallucinations and sleep disorder. LESSONS: The case report demonstrates that anti-IgLON5 and anti-GABAB-receptor antibodies can coexist in the same patient whereas clinical leading symptoms are determined by those antibodies that were tested positive in cerebrospinal fluid.


Assuntos
Moléculas de Adesão Celular Neuronais/sangue , Moléculas de Adesão Celular Neuronais/líquido cefalorraquidiano , Encefalite/imunologia , Antagonistas de Receptores de GABA-B/sangue , Doença de Hashimoto/imunologia , Administração Intravenosa , Autoanticorpos/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/etiologia , Disartria/diagnóstico , Disartria/etiologia , Encefalite/diagnóstico , Encefalite/tratamento farmacológico , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Glucocorticoides/uso terapêutico , Alucinações/diagnóstico , Alucinações/etiologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Plasmaferese/métodos , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia , Resultado do Tratamento
17.
Ann Hematol ; 98(8): 1961-1972, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31065733

RESUMO

Peripheral T cell lymphomas (PTLs) have a globally poor prognosis. The CHOP regimen shows insufficient efficacy; first-line consolidation with autologous stem cell transplantation (auto-SCT) is a promising strategy but has never been confirmed by randomized data. We analyzed retrospectively 906 patients diagnosed with PTL between 1999 and 2015. Chemotherapy was given to 862 patients, and 412 of them were < 60 years. In this subset, we compared induction with CHOP (n = 113) vs. CHOEP (n = 68) and tested auto-SCT (n = 79) vs. no SCT (n = 73) in the intent-to-treat analysis. The median age of the whole cohort at diagnosis was 60 years (range; 18-91); the median follow-up was 4.3 years (range; 0.1-17.8). A shorter overall survival (OS) was associated with the male gender, age ≥ 60 years, stage III/IV, performance status ≥ 2, bulky tumor ≥ 10 cm, and elevated LDH. CHOEP induction showed a better 5-year PFS (25.0% vs. 32.9%; p.001), and 5-year OS (65.6% vs. 47.6%; p.008) than CHOP. Auto-SCT compared to no SCT brought a 5-year OS of 49.2% vs. 59.5% (p.187). Auto-SCT did not influence the OS in low-risk or low-intermediate risk PTLs. The high-intermediate and high-risk IPIs displayed a worse 5-year OS in auto-SCT arm (17.7% vs.46.2%; p.049); however, 73.9% of the patients never received planned auto-SCT. Our population-based analysis showed the superiority of CHOEP over CHOP in first-line treatment. We confirm the 5-year OS of around 50% in PTLs undergoing auto-SCT. However, the intended auto-SCT could not be given in 73.9% of the high-risk PTLs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Progressão da Doença , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Autólogo , Vincristina/uso terapêutico
18.
Lupus ; 28(5): 591-596, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31066646

RESUMO

Lupus nephritis is the most common organ-threatening manifestation of systemic lupus erythematosus. The current standard of care for patients is treatment with a combination of steroids plus either mycophenolate mofetil (MMF) or cyclophosphamide. However, these medications are associated with considerable toxicity and suboptimal efficacy. This retrospective propensity analysis of data from 63 matched patients enrolled in two of the largest active lupus nephritis controlled trials, ALMS and AURA, suggests that the high dose regimen of MMF and steroids as described in the 2012 American College of Rheumatology lupus nephritis guidelines may not be necessary in all lupus nephritis patients. A lower dose regimen may result in better long-term safety, including a reduction in lymphoproliferative disorders, skin cancers and steroid related side effects, without compromising efficacy. An ongoing randomized controlled double-blind phase 3 study, AURORA (NCT03021499), is investigating renal response in 358 patients randomized to receive a low dose regimen containing voclosporin, MMF and steroid therapy as used in the AURA trial. It is anticipated that the AURORA study and its blinded two-year extension will provide important long-term outcome data.


Assuntos
Ciclofosfamida/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Padrão de Cuidado , Esteroides/uso terapêutico , Adolescente , Adulto , Idoso , Ciclosporina/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Modelos Logísticos , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Estudos Retrospectivos , Tempo para o Tratamento , Resultado do Tratamento , Adulto Jovem
19.
BMC Cancer ; 19(1): 506, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138229

RESUMO

BACKGROUND: Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression. METHODS: PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of life. Exploratory, translational research aims to evaluate immune biomarkers, extracellular vesicles, cell death biomarkers and the gut microbiome. DISCUSSION: In this study, a combination of PD-1 blockade, radiation and immune/environmental-targeting compounds is tested, aiming to tackle the tumor microenvironment and induce anti-tumor immunity. Translational research is performed to discover biomarkers related to the mode of action of the combination. TRIAL REGISTRATION: EU Clinical Trials Register: EudraCT 2016-001569-97 , registered on 19-6-2017. Clinicaltrials.gov: NCT03192059 , registered on 19-6-2017.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Endométrio/terapia , Recidiva Local de Neoplasia/terapia , Sarcoma/terapia , Neoplasias do Colo do Útero/terapia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Quimiorradioterapia , Curcumina/administração & dosagem , Curcumina/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Reposicionamento de Medicamentos , Feminino , Humanos , Imunoterapia , Lansoprazol/administração & dosagem , Lansoprazol/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento , Vitamina D/administração & dosagem , Vitamina D/uso terapêutico
20.
Medicine (Baltimore) ; 98(22): e15927, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145359

RESUMO

INTRODUCTION: A network meta-analysis was conducted to regard the effects of available immunosuppressive medications in pediatric frequently-relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). METHODS: We reviewed systematically 26 randomized controlled trials (1311 patients) that compared any of the following immunosuppressive agents to placebo/nontreatment (P/NT) or another drug for FRNS/SDNS treatment in children. RESULTS: The main outcomes were efficacy and acceptability. At the 6-month, cyclophosphamide, chlorambucil, levamisole, and rituximab had better efficacy than P/NT (odds ratio [OR]: 0.09, 0.03, 0.28, and 0.07, respectively); cyclophosphamide was significantly more effective than azathioprine and chlorambucil. At 12 months, cyclophosphamide, chlorambucil, cyclosporine, levamisole, and rituximab had better efficacy than P/NT (0.10, 0.03, 0.10, 0.23, and 0.07, respectively); Chlorambucil were found to be more efficacious than levamisole and MMF (0.12 and 0.09, respectively). At 24 months, cyclophosphamide, chlorambucil, and levamisole had better efficacy than P/NT (0.09, 0.04, and 0.03, respectively); cyclophosphamide had better efficacy than cyclosporine and vincristine (0.17 and 0.39, respectively). CONCLUSION: No significant differences in acceptability were found. Our results suggest that cyclophosphamide may be preferred initially in children with FRSN/SDNS, chlorambucil, and rituximab may be acceptable medications for patients with FRSN/SDNS. Long-term follow-up trials focused on gonadal toxicity and limitation of maximum dosage of cyclophosphamide should been carried out.


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Clorambucila/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Lactente , Levamisol/uso terapêutico , Masculino , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Rituximab/uso terapêutico , Prevenção Secundária/métodos , Resultado do Tratamento
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