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1.
BJUI Compass ; 3(1): 37-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35475152

RESUMO

Objectives: Multimodal kidney-preserving (MKP) strategies may be an option for patients with localised or locally advanced high-risk upper tract urothelial carcinoma (UTUC) who have a relative contraindication for nephroureterectomy (NU). Materials and methods: We studied patients with UTUC who were managed with MKP strategies, consisting of systemic anticancer therapy, with or without local/topical strategies after endoscopic control of intraluminal tumours. Primary end points were overall survival (OS) and progression-free survival (PFS). Results: Fourteen patients received MKP treatment between August 2013 and April 2020. Median baseline estimated glomerular filtration rate was 43 mL/min/1.73m2. MKP was mainly pursued to avoid dialysis (10/14, 71%), followed by low performance status and/or comorbidities (2/14, 14%). All patients had received systemic therapy: chemotherapy (64%) and immunotherapy (36%). Endoscopic control and/or laser ablation was feasible in 7 (50%) patients. Calculated overall risk of non-organ confined disease was 35%. Predicted 2-year and 5-year relapse-free probability (RFP) was 74% (24-92%) and 62% (10-85%), respectively. Median follow-up was 31 months (95% CI: 22.6, NE), median OS was 48.1 months (95% CI: 48.1, NE) and 2-year OS probability was 0.89 (95% CI: 0.71, 1). Median metastases-free survival was 48.1 months (95% CI: 26.8, NE), median PFS was 22.4 months (95% CI: 15.6, NE) and 2-year PFS probability was 0.48 (0.26, 0.89). Conclusion: Management of high-risk localised or locally advanced UTUC with MKP strategies was associated with good tolerance, preservation of renal function, and comparable PFS and OS to predicted in vulnerable patients. Prospective studies with more patients are needed to evaluate these possible benefits relative to current standards.

2.
Expert Opin Pharmacother ; 23(4): 431-438, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35060807

RESUMO

INTRODUCTION: Unique among hematologic malignancies, blastic plasmacytoid dendritic cell neoplasm (BPDCN) affects multiple compartments including bone marrow, hematologic, lymphatic, dermatologic, and central nervous systems (CNS). Treating BPDCN is challenging, historically, as patients display refractoriness to chemotherapy and absence of long-term remissions in many cases not treated with hematopoietic stem cell transplantation. Discovering the prevalent overexpression of surface receptor CD123 (IL3-Rα) on BPDCN cells led to development of tagraxofusp, a novel anti-CD123 agent for patients with BPDCN. AREAS COVERED: Herein, the authors discuss the preclinical development and phase I/II clinical studies, which led to the approval of tagraxofusp. They discuss the current treatment landscape of BPDCN with tagraxofusp alone or combined with chemotherapy and highlight several ongoing clinical trials involving combinations of tagraxofusp with novel targeted therapeutics for BPDCN. EXPERT OPINION: Tagraxofusp has significantly improved the treatment landscape for patients with newly diagnosed BPDCN and has led to investigative efforts and augmentation of various strategies of targeting CD123, such as antibody-drug conjugates and anti-CD123 chimeric antigen receptor T-cells. However, relapsed/refractory disease and CNS-involvement of BPDCN remain therapeutic challenges. The authors recommend that healthcare providers consider multiple-agent clinical trial approaches and adequate CNS-prophylaxis for all patients with BPDCN.


Assuntos
Células Dendríticas , Neoplasias Hematológicas , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Células Dendríticas/patologia , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Subunidade alfa de Receptor de Interleucina-3/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico
3.
Blood Adv ; 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35061885

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive blood cancer, often involving skin, bone marrow, lymph nodes, as well as central nervous system (CNS) involvement in 20-30% of patients. Despite significant progress in CD123- and BCL-2-targeted therapy, most patients are not cured outside of hematopoietic stem cell transplant (HSCT), and CNS relapses are being observed quite frequently. Combination approaches with both targeted and chemotherapy agents plus incorporation of prophylactic CNS-directed therapy are urgently needed. In this setting, we sought to analyze outcomes of the cytotoxic chemotherapy backbone regimen hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (HCVAD) in BPDCN. We conducted a retrospective analysis of patients with BPDCN (n=100), evaluating complete remission (CR) and median overall survival (OS) among three groups: those who received frontline HCVAD-based (n=35) vs SL-401 (n=37) vs other regimens (n=28). HCVAD-based regimens yielded higher CR (80% vs 59% vs 43%, p=0.01). There was no significant difference in OS (28.3 vs 13.7 vs 22.8 months p=0.41), nor significant difference in remission duration probability among treatment groups (38.6 vs NR vs 10.2 months; p=0.24). HSCT was performed in 51% vs 49% vs 38% respectively (p=0.455). These results suggest a continued important role for HCVAD-based chemotherapy for BPDCN, even in the modern targeted-therapy era, with high CR rates in the frontline setting. Further studies must establish the clinical activity, feasibility, and safety, of doublet/triplet combinations of targeted therapies plus cytotoxic agents and addition of CNS prophylaxis, with ultimate goal of durable long-term remissions for patients with BPDCN.

4.
Leuk Lymphoma ; 63(1): 19-30, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34486917

RESUMO

Plasmacytoid dendritic cells (pDCs) serve as immunoregulatory antigen-presenting cells that play a role in various inflammatory, viral, and malignant conditions. Malignant proliferation of pDCs is implicated in the pathogenesis of certain hematologic cancers, specifically blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myelogenous leukemia with clonal expansion of pDC (pDC-AML). In recent years, BPDCN and pDC-AML have been successfully treated with targeted therapy of pDC-specific surface marker, CD123. However, relapsed and refractory BPDCN remains an elusive cancer, with limited therapeutic options. CD303 is another specific surface marker of human pDCs, centrally involved in antigen presentation and immune tolerance. Monoclonal antibodies directed against CD303 have been studied in preclinical models and have achieved disease control in patients with cutaneous lupus erythematosus. We performed a comprehensive review of benign and malignant disorders in which CD303 have been studied, as there may be a potential future CD303-directed therapy for many of these conditions.


Assuntos
Neoplasias Hematológicas , Lectinas Tipo C , Leucemia Mieloide Aguda , Glicoproteínas de Membrana , Receptores Imunológicos , Apresentação do Antígeno , Células Dendríticas , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico
5.
J Immunother ; 45(1): 13-24, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469413

RESUMO

Data regarding clinical outcomes and management of hematological manifestations of immune checkpoint inhibition (ICI) is limited to case reports, series, and a few retrospective reviews. We aimed to determine the rate of response of hematological immune-related adverse events (irAEs) to immunosuppressive therapy. MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to the present day. Retrospective reports were included without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration's tool. The primary outcome of this study was the rate of response to immunosuppression. Eighty studies (14 case series and 66 individual case reports) were analyzed with a total of 135 patients with ICI-related hematological irAEs. Data analysis showed an average proportional response rate to immunosuppression among hematological irAE entities of 50% (range: 25%-70%). The heterogeneity index (I2) was 0% among reports within each entity. There is a wide spectrum of hematological manifestations to ICI therapy, and to date there is no large randomized-controlled trial data to evaluate the efficacy of treatment strategies for hematological irAEs. We found a variable overall response rate to immunosuppression therapy of around 50%, without statistically significant heterogeneity among different irAE types but significant differences among the different countries of publication. Future studies evaluating the optimal dose and duration of immunosuppressive agents for patients with hematological irAEs should be undertaken.


Assuntos
Inibidores de Checkpoint Imunológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
6.
Clin Genitourin Cancer ; 19(6): e401-e408, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34625389

RESUMO

INTRODUCTION: Renal medullary carcinoma (RMC) is a rare and lethal renal cell carcinoma characterized by the loss of tumor suppressor SMARCB1. Molecular profiling studies have suggested that RMC cells may be vulnerable to therapies that generate DNA damage, such as the combination of the nucleoside analog gemcitabine, and topoisomerase inhibitor doxorubicin. PATIENTS AND METHODS: We retrospectively analyzed the records of patients with RMC treated with gemcitabine plus doxorubicin at our institution between January 2005 and September 2020. Best radiographic response and disease progression (RECIST v1.1) were assessed by a blinded radiologist. RESULTS: Sixteen patients were included in the study. All but 1 patient (93.8%) received prior platinum-based chemotherapy. Gemcitabine was given intravenously at 900-1200 mg/m2 and doxorubicin at 40-50 mg/m2 intravenously every 2 weeks. Three patients (18.8%) achieved partial response and 7 (43.8%) patients achieved stable disease. The median progression-free survival was 2.8 months (95% CI, 0-6.0). Median overall survival (OS) from gemcitabine plus doxorubicin initiation was 8.1 months (95% CI, 4.6-11.7) and OS from diagnosis was 15.5 months (95% CI, 4.2-26.8 months). There were no grade ≥ 4 AEs; grade 3 AEs were cytopenias (18.8%), nausea (12.5%), fatigue (12.5%), and cardiotoxicity (6.2%). No somatic alterations were detected in the 9 patients tested by targeted next generation sequencing assays. CONCLUSION: Gemcitabine plus doxorubicin was well tolerated and demonstrated clinical activity in patients with platinum-refractory RMC, with a subset of patients experiencing durable responses lasting longer than 6 months. Further investigation is warranted to determine biomarkers of sensitivity and target mechanisms of resistance.


Assuntos
Carcinoma Medular , Carcinoma de Células Renais , Neoplasias Renais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/análogos & derivados , Doxorrubicina/efeitos adversos , Humanos , Neoplasias Renais/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
7.
Expert Rev Hematol ; 14(11): 993-1004, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34607517

RESUMO

INTRODUCTION: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with historically poor outcomes for patients, often refractory to traditional chemotherapy. Recent research has focused on targeted therapy to improve responses and limit potential toxicity. AREAS COVERED: CD123 (also known as IL-3 Rα) is a cell surface marker and attractive therapeutic target for many myeloid malignancies, particularly BPDCN, whose cells ubiquitously overexpress CD123. We review the history of CD123 research regarding BPDCN, recent advances including FDA approval of tagraxofusp (formerly SL-401) for BPDCN, and ongoing clinical studies utilizing novel therapeutic strategies to target CD123. EXPERT OPINION: The approval of tagraxofusp for the treatment of BPDCN in December 2018 drastically changed the treatment landscape for patients with this rare neoplasm. While tagraxofusp is better tolerated than traditional multi-agent chemotherapy regimens, it requires close monitoring and sound clinical judgment by providers to prevent and mitigate severe treatment-related complications with special attention to the recognition and management of capillary leak syndrome (CLS). Several other promising strategies for targeting CD123 in BPDCN are currently under investigation, including antibody-drug conjugates, T-cell engagers, and CAR-T cellular therapeutics. These CD123 targeted approaches may soon become standard of care for patients with this difficult to treat malignancy.


Assuntos
Neoplasias Hematológicas , Transtornos Mieloproliferativos , Neoplasias Cutâneas , Células Dendríticas/metabolismo , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Subunidade alfa de Receptor de Interleucina-3/uso terapêutico , Transtornos Mieloproliferativos/metabolismo
8.
Clin Lymphoma Myeloma Leuk ; 21(11): 734-740, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34226167

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from the aberrant transformation of plasmacytoid dendritic cells (pDCs) and involving skin, bone marrow, lymph nodes, and central nervous system. Characteristically unique from other myeloid neoplasms, BPDCN cells express CD4, CD56, and CD123 as well as TCL-1 and TCF4 in almost all cases. Historically, this malignancy has exhibited a poor prognosis, with median survival of less than 2 years. Traditional treatment approaches have involved conventional cytotoxic chemotherapy followed by hematopoietic stem cell transplantation; however, patients frequently relapse with chemotherapy-resistant disease. We have recently entered a modern era of therapy with targeting of CD123, with first-in-class agent tagraxofusp, a CD123- targeted agent approved by the US Food and Drug Administration for therapy of patients with BPDCN ages 2 and older. Relapsed and refractory BPDCN remains an elusive therapeutic challenge, but better understanding of the underlying pathophysiology has led to the development of other CD123-targeted agents and combination therapy, as well as agents targeting beyond CD123. Specifically, the use of venetoclax in targeting BCL2 has been promising in BPDCN treatment. This review will focus on the underlying diagnostic markers of BPDCN which have led to novel targeted treatment strategies, as well as future directions in therapy we can expect in coming years.


Assuntos
Antineoplásicos/uso terapêutico , Células Dendríticas/patologia , Neoplasias Hematológicas/tratamento farmacológico , Antineoplásicos/farmacologia , Feminino , Humanos , Masculino
10.
Cureus ; 13(3): e14180, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33936891

RESUMO

Due to the infrequently reported location, malignancies of the ear are usually misdiagnosed at the time of first presentation. To the best of our knowledge, there have been no reports in literature regarding diffuse large B-cell lymphoma (DLBCL) presenting as an ear mass, as was seen in our patient. We describe a case of a 38-year-old gentleman who presented with four months of worsening dyspnea on exertion and nonproductive cough. On exam there was a 4 cm x 5 cm erythematous, non-tender, and immobile mass on the right lower ear in the intertragic notch, sparing the lobe. CT of the neck and chest revealed prominent cervical lymph nodes and a diffusely spread circumferential soft tissue mediastinal mass involving the lungs, pleura, and pericardium. Malignancy was suspected, so the right ear mass was biopsied. Findings were consistent with DLBCL, germinal center B-type. This case provides a rare example of DLBCL presenting as an ear mass in a 38-year-old male with a chronic cough. We believe that prompt radiological evaluation of the chronic nonresolving cough may have helped in timely diagnosis of the malignancy, possibly halting the extensive infiltrative spread of disease, and thereby reducing the morbidity that the patient eventually suffered.

11.
Front Cardiovasc Med ; 8: 638943, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33969007

RESUMO

Background: Pericardiocentesis is an important diagnostic and therapeutic tool for cancer-associated pericardial effusion. Limited safety and outcomes data exists regarding the management of malignancy-related pericardial effusion in patients with thrombocytopenia. Objectives: Our study aimed to analyze prognostic factors and overall survival (OS) after pericardiocentesis in thrombocytopenic cancer patients. Methods and Results: A retrospective review of 136 thrombocytopenic cancer patients who underwent primary percutaneous pericardiocentesis was performed. Degree of thrombocytopenia was classified by platelet count recorded on day of pericardiocentesis: 75-149 × 103 cells/µL (41%); 50-74 × 103 cells/µL (10%); 25-49 × 103 cells/µL (24%); <25 × 103 cells/µL (25%). Median OS was 2.6 months and median follow-up was 37.4 months. Kaplan-Meier survival analysis showed significant OS differences among thrombocytopenia severity groups (p = 0.023), and worse OS with platelets <100 vs. ≥100 × 103 cells/µL (p = 0.031). By univariate analysis, thrombocytopenia severity was associated with increased risk of death (HR 0.993; 95% CI 0.989-0.997; p = 0.002). Poor prognostic factors for OS were advanced cancer, malignant effusion, elevated international normalized ratio (INR), quantity of platelet transfusions, and platelet transfusion resistance. However, thrombocytopenia severity became insignificant for OS (p = 0.802), after adjusting for advanced cancer and INR. Conclusions: For patients with malignancy-related large pericardial effusion and thrombocytopenia, pericardiocentesis is a feasible intervention and should be considered due to low complication rates. There is no absolute contraindication to pericardiocentesis in case of hemodynamic instability, even with severe thrombocytopenia.

12.
Leuk Lymphoma ; 62(9): 2253-2260, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33749512

RESUMO

There is growing Internet and social media use among patients with rare blood cancers, notably myeloproliferative neoplasms (MPNs). A 38-item online questionnaire was developed to assess patients' (n = 983) disease understanding and use of online resources regarding MPN. Many responders (74%) reported unawareness of additional mutations beyond their primary molecular marker(s); 32% were unsure of their prognostic risk stratification. Additionally, 89% reported using online resources (Facebook (61%); Google/Google+ (42%); YouTube (34%); blogs (26%); Twitter (5%)) to seek information about MPN. Despite this, results showed many gaps in patients' basic disease knowledge. Our findings suggest an important difference in social media habits between physicians and patients: physicians are rapidly adopting Twitter as their preferred medium for sharing medical knowledge; however, patients often prefer other social mediums. Educational campaigns should be designed in more personalized ways, aiming to fit a variety of online platforms to maximize reach and impact for patients with MPN.


Assuntos
Neoplasias Hematológicas , Transtornos Mieloproliferativos , Neoplasias , Mídias Sociais , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Inquéritos e Questionários
13.
Int J Cancer ; 149(2): 387-393, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33739450

RESUMO

Nivolumab plus ipilimumab (nivo/ipi) is an approved therapy for patients with intermediate-risk or poor-risk metastatic renal cell carcinoma (mRCC). Clinical factors that guide the selection of this regimen for patients with mRCC are urgently needed. We retrospectively analyzed medical records of patients with mRCC who were hospitalized at MD Anderson Cancer Center because of cancer-related symptoms and received their first cycle of nivo/ipi in the inpatient setting. Clinical parameters, including demographics, histology, clinical history, response, and survival, were collected. The 4-month survival probability, progression-free survival (PFS), and overall survival (OS) were calculated using Kaplan-Meier methods. Between November 2017 and 21 June 2020 patients were identified that fit the search: 19 patients (91%) had poor-risk disease based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score; 17 patients (81%) had ≥4 risk factors; and 9 patients (43%) had sarcomatoid features on histology. Shortness of breath (28%) and abdominal pain (19%) were the two most common reasons for hospitalization. Partial response was achieved in 14% (3/21) of patients. Median PFS for all patients was 1.7 months (95% CI 0-3.9); median OS for all patients was 1.7 months (95% CI 0-4.2); and the 4-month survival probability was 36% (95% CI 25%-47%). In this retrospective study, patients with intermediate-risk or poor-risk mRCC who are hospitalized at a large tertiary referral center for cancer-related symptoms derive limited clinical benefit from nivo/ipi when started in the inpatient setting. Alternative, more effective systemic therapies should be considered for these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Ipilimumab/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Nivolumabe/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Determinação de Ponto Final , Feminino , Hospitalização , Humanos , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento
14.
Transfus Apher Sci ; 60(3): 103096, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33612449

RESUMO

BACKGROUND: Platelet transfusion refractoriness (PTR) secondary to human leukocyte antigen (HLA) alloimmunization is a challenge in the treatment of hematology-oncologypatients and increases the risk of morbidity and mortality from bleeding events. Guidelines for treating PTR have not been clearly described in literature. We aim to describe the practice patterns for the management of PTR secondary to HLA alloimmunization, and to assess the mortality, thrombosis and bleeding-related clinical outcomes at 30 days from diagnosis. METHODS: A retrospective review of 51 cases of PTR secondary to HLA alloimmunization were analyzed. RESULTS: The majority of patients (98 %) had a diagnosis of hematological malignancy of which 88.2 % were undergoing active chemotherapy. Clinically relevant bleeding, by ISTH criteria, was observed in 33.3 %; hemorrhagic shock was diagnosed in 7%. The rate of bleeding-related mortality was estimated at 7.8 %. The use of antifibrinolytics and plasma products (including intravenous immunoglobulin) was more common in cases with major versus non-major bleeding. Grade A or B1U HLA matched products were available in less than half of cases. CONCLUSIONS: There is heterogeneity in the management of the bleeding risk and bleeding events during PTR, with antifibrinolytics more commonly used in patients who suffered severe bleeding. Grade A and B1U HLA-matched platelets are not always readily available, and HLA-typing and HLA-antibody testing are not always performed prior to PTR. Prospective randomized control trials may help to determine the safety and efficacy of antifibrinolytics and other supportive measures in the management of PTR.


Assuntos
Plaquetas/imunologia , Isoanticorpos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
18.
Cureus ; 12(8): e9867, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32963908

RESUMO

Hydralazine-induced lupus syndrome (HILS) is a rare clinical entity with variable manifestations. Pericardial involvement is an uncommon but serious manifestation of the condition. In this report, we present a case of large symptomatic pericardial effusion secondary to HILS. We highlight the important considerations in the evaluation and management of this rare syndrome. HILS should be considered in the differential diagnosis for cardiac tamponade of otherwise unclear etiology in patients taking 100 mg daily or more of hydralazine for longer than three months. A temporal association between the offending drug and presenting symptoms, resolution of symptoms upon discontinuation, and a positive anti-histone antibody test can all support the diagnosis of this syndrome.

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