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1.
Int J Hematol ; 112(5): 666-673, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32783165

RESUMO

We retrospectively analyzed 51 patients with solitary plasmacytoma diagnosed from October 2002 to September 2018 from a cohort of 3575 patients with plasma cell dyscrasias registered in the Kansai Myeloma Forum. Twenty-seven patients had solitary bone plasmacytoma (SBP) and 24 had extramedullary plasmacytoma (EMP), with prevalence of 0.8% and 0.7%, respectively. The most frequent M protein was IgG (40%) in SBP, whereas non-secretory proteins were most frequent (50%) in EMP. Five-year overall survival was 78.2% in SBP and 80.8% in EMP (P = 0.894). Among patients with SBP, 44% progressed to MM with a median time of 10.5 months (2.4-93.3 months), whereas 8% of EMP patients progressed to MM with a median time of 18.6 months (13.0-24.2 months). The most frequent treatment was radiotherapy (41%) or observation (41%) in SBP, and chemotherapy (54%) in EMP. No statistically significant difference was observed upon univariate analysis of prognostic factors including age, sex, performance status, and IgG M protein. Our results suggest that there are biological differences between SBP and EMP in real-world settings.


Assuntos
Neoplasias Ósseas , Plasmocitoma , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Progressão da Doença , Feminino , Humanos , Imunoglobulina G , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Proteínas do Mieloma , Plasmocitoma/epidemiologia , Plasmocitoma/mortalidade , Plasmocitoma/patologia , Plasmocitoma/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
2.
Dermatol Online J ; 26(5)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621712

RESUMO

Pyoderma gangrenosum (PG) is a rare ulcerative skin condition. It can be associated with a number of systemic diseases. Association with monoclonal gammopathy of undetermined significance (MGUS) is uncommon, but prognosis may be different depending upon the type of MGUS. Cases of MGUS- related PG reported in the literature with data concerning evolution and treatment were identified through a PubMed search. A patient with recurrent PG in the setting of a MGUS-IgA-? in our department was also included. In total, 10 cases were identified. Only the two cases with Ig populations other than IgA improved without recurrence after treatment of the PG. All the patients with MGUS-IgA showed recurrences. Early multiple myeloma was proposed for three patients with MGUS-IgA-related PG. Second or third line treatments were necessary in some cases.


Assuntos
Glucocorticoides/uso terapêutico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Prednisolona/uso terapêutico , Pioderma Gangrenoso/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Pioderma Gangrenoso/complicações , Recidiva
3.
Nat Commun ; 11(1): 1917, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317634

RESUMO

The evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2nd-3rd decades of life. We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection.


Assuntos
Regulação Neoplásica da Expressão Gênica , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/genética , Desaminase APOBEC-1/metabolismo , Citidina Desaminase/metabolismo , Análise Mutacional de DNA , Detecção Precoce de Câncer , Exoma , Genética , Centro Germinativo/patologia , Humanos , Modelos Lineares , Antígenos de Histocompatibilidade Menor/metabolismo , Mutação , Proteínas/metabolismo , Edição de RNA , RNA Mensageiro , Análise de Célula Única
4.
Bull Cancer ; 107(4): 428-437, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32204890

RESUMO

INTRODUCTION: An in-patient clinical service has been set up in March 2016 in the Occupational Diseases Center of Brest University Hospital, France, to seek for work-relatedness of diseases in patients hospitalized into the oncology and hematology departments. We present here data after two years of existence. METHODS: All cases of cancers or malignant hematological diseases (ICD-10 codes C00 to C97 and D37 to D48) seen between March 1, 2016, and March 1, 2018, have been identified. We present sociodemographic data, occupational exposures, occupation, business sector, and tobacco consumption. The causation level between the disease and each of the occupational exposures has been rated as strong, intermediate, weak or null by the occupational medicine specialist of the Occupational Diseases Center. RESULTS: Among the 196 patients encountered, there are 127 work-related diseases and 82 of these had one occupational exposure rated as strong or intermediate. The most frequent occupational hazards were asbestos (48 cases) and ionizing radiation (23 cases). The most frequent business sectors were metallurgy, mechanical engineering, and agriculture. Lung cancer was the most frequently reported disease (49 cases). DISCUSSION: . We identified well-known couples with occupational exposures and diseases, such as asbestos and lung cancer. We also identified a link between pesticides and leukemias. This in-patient clinical service is helpful to identify work-related exposures and in helping patients to get compensated.


Assuntos
Neoplasias/etiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Asbestos/toxicidade , Carcinógenos/toxicidade , Feminino , França , Hospitais Universitários , Humanos , Leucemia/induzido quimicamente , Neoplasias Pulmonares/etiologia , Linfoma/etiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Exposição Ocupacional/classificação , Serviços de Saúde do Trabalhador/organização & administração , Ocupações , Praguicidas/toxicidade , Exposição à Radiação/efeitos adversos , Radiação Ionizante , Neoplasias da Bexiga Urinária/etiologia , Adulto Jovem
5.
Scand J Immunol ; 91(5): e12870, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32034957

RESUMO

Two novel enzyme-linked immunosorbent assays (ELISAs), designed to detect complexes containing DNA, leucocyte calprotectin and S100A12 proteins, were generated for improved specificity and rapid measurement of neutrophil extracellular traps (NETs). The assays were applied on plasma and serum samples from blood donors for establishment of reference values, and from patients with multiple myeloma (MM) or rheumatoid arthritis (RA) in order to examine putatively increased values in the two different inflammatory conditions. Although NETs were hardly detectable in healthy individuals, NET levels were as expected highly and statistically significantly increased in RA patients. The detection of statistically significantly increased NET levels in MM is a novel finding.


Assuntos
Artrite Reumatoide/etiologia , Artrite Reumatoide/metabolismo , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/metabolismo , Adulto , Idoso , Artrite Reumatoide/patologia , Doadores de Sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Projetos Piloto , Adulto Jovem
6.
JAMA Dermatol ; 156(3): 270-279, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31940000

RESUMO

Importance: Necrobiotic xanthogranuloma (NXG) is a non-Langerhans cell histiocytosis classically associated with paraproteinemia attributable to plasma-cell dyscrasias or lymphoproliferative disorders. Despite the morbidity of NXG, the literature is limited to case reports and small studies, and diagnostic criteria are lacking. Objective: To evaluate the characteristics of NXG and propose diagnostic criteria. Design, Setting, and Participants: This multicenter cross-sectional study was conducted at tertiary academic referral centers and followed by a systematic review and a consensus exercise. The multicenter cohort included patients with NXG diagnosed at the Brigham and Women's and Massachusetts General Hospitals (2000-2018), the University of Iowa Hospitals and Clinics (2000-2018), and the University of Pennsylvania Health System (2008-2018). The systematic review was conducted in 2018 and included patients with NXG identified in the Cochrane, Ovid EMBASE, PubMed, and Web of Science databases. The consensus exercise was conducted by 8 board-certified dermatologists to identify diagnostic criteria. Main Outcomes and Measures: Demographic factors, comorbidities, clinical features, and treatment response. Results: Of 235 included patients with NXG (34 from the multicenter cohort and 201 from the systematic review results), the mean (SD) age at presentation was 61.6 (14.2) years; 147 (62.6%) were female. Paraproteinemia was detected in 193 patients (82.1%), most often IgG-κ (117 patients [50.0%]). A malignant condition was detected in 59 patients (25.1%), most often multiple myeloma (33 patients [14.0%]). The overall rate of paraproteinemia and/or a malignant condition was 83.8% (197 patients). In the multicenter cohort, evolution of paraproteinemia into multiple myeloma was observed up to 5.7 years (median [range], 2.4 [0.1-5.7] years) after NXG presentation. Cutaneous lesions consisted of papules, plaques, and/or nodules, typically yellow or orange in color (113 of 187 [60.4%]) with a periorbital distribution (130 of 219 [59.3%]). The eye was the leading site of extracutaneous involvement (34 of 235 [14.5%]). In the multicenter cohort, intravenous immunoglobulin had the best treatment response rate (9 of 9 patients [100%]), followed by antimalarial drugs (4 of 5 patients [80%]), intralesional triamcinolone (6 of 8 patients [75%]), surgery (3 of 4 patients [75%]), chemotherapy (8 of 12 patients [67%]), and lenalidomide or thalidomide (5 of 8 patients [63%]). The consensus exercise yielded 2 major criteria, which were (1) clinical and (2) histopathological features consistent with NXG, and 2 minor criteria, consisting of (1) paraproteinemia, plasma-cell dyscrasia, and/or other associated lymphoproliferative disorder and (2) periorbital distribution of cutaneous lesions. In the absence of foreign body, infection, or another identifiable cause, fulfillment of both major and at least 1 minor criterion were proposed to establish the diagnosis of NXG. Conclusions and Relevance: Necrobiotic xanthogranuloma is a multisystem disorder associated with paraproteinemia and malignant conditions. The proposed diagnostic criteria may advance clinical research and should be validated.


Assuntos
Xantogranuloma Necrobiótico/diagnóstico , Paraproteinemias/etiologia , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/etiologia , Xantogranuloma Necrobiótico/fisiopatologia , Xantogranuloma Necrobiótico/terapia , Paraproteinemias/epidemiologia , Estudos Retrospectivos
8.
Probl Radiac Med Radiobiol ; 24: 426-438, 2019 Dec.
Artigo em Inglês, Ucraniano | MEDLINE | ID: mdl-31841484

RESUMO

OBJECTIVE: Experimental study of the effect profile of bortezomib in the plasma cell myeloma (PCM) patients depend- ing on a specific phenotype carrier state and a pharmacochemical characteristics of ABO system glycoproteins. MATERIALS AND METHODS: The research was conducted on the 104 PCM patients, including the Chornobyl NPP acci- dent survivors (n = 49) and 65 study subjects in the comparison group. Immunogenetic criteria for positive response to the applied treatment protocols were issued according to the duration of remission, absence of infectious com- plications, and evidence of chronic renal failure as a disease complication. RESULTS: Possibility of glycoproteins A and B participation in the formation of human biological individuality at a level of protein-protein interaction with antineoplastic drug bortezomib, which is widely used in cancer management prac- tice, in particular in the PCM treatment is considered. The glycoprotein B was shown being a selective target for borte- zomib, slowing down the recognition and interaction of antigen B with monoclonal anti-B antibody, while the agglu- tination period lengthens at that by 66 %. Assumption that the formation of bortezomib complex with glycoprotein B provides a background for interaction with the key reaction of proteasome 26S inhibition, which to some extent con- tributes to the drug effect retardation was confirmed through the quantum-chemical calculations. Equilibrium is shift- ed toward the main reaction leading to a higher drug efficacy in patients with blood groups O (I) and A (II). CONCLUSIONS: Since the complexation occurs predominantly in alkaline medium the administration of drugs with alkaline reaction should be restricted for at least round the clock after administration of bortezomib according to its half-life in plasma in patients with B (III) blood group and chronic renal failure.


Assuntos
Sistema ABO de Grupos Sanguíneos/metabolismo , Complexo Antígeno-Anticorpo/metabolismo , Antineoplásicos/farmacologia , Bortezomib/farmacologia , Acidente Nuclear de Chernobyl , Glicoproteínas/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Sistema ABO de Grupos Sanguíneos/genética , Sistema ABO de Grupos Sanguíneos/imunologia , Alelos , Complexo Antígeno-Anticorpo/genética , Antineoplásicos/química , Antineoplásicos/farmacocinética , Bortezomib/química , Bortezomib/farmacocinética , Estudos de Casos e Controles , Eritrócitos/imunologia , Eritrócitos/metabolismo , Expressão Gênica , Glicoproteínas/genética , Glicoproteínas/imunologia , Humanos , Modelos Moleculares , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/genética , Mieloma Múltiplo/imunologia , Plasmócitos/efeitos dos fármacos , Plasmócitos/imunologia , Plasmócitos/patologia , Ligação Proteica , Teoria Quântica , Exposição à Radiação/efeitos adversos , Sobreviventes , Termodinâmica , Resultado do Tratamento
9.
BMC Cancer ; 19(1): 1147, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775673

RESUMO

BACKGROUND: The advent of the immunomodulatory imide drugs (IMiDs) lenalidomide and thalidomide for the treatment of patients with plasma cell myeloma (PCM), has contributed to more than a doubling of the overall survival of these individuals. As a result, PCM patients join survivors of other malignancies such as breast and prostate cancer with a relatively new clinical problem - second primary malignancies (SPMs) - many of which are a result of the treatment of the initial cancer. PCM patients have a statistically significant increased risk for acute myeloid leukemia (AML) and Kaposi sarcoma. IMiD treatment has also been associated with an increased risk of myelodysplastic syndrome (MDS), AML, and squamous cell carcinoma of the skin. However, within these overlapping groups, acute lymphoblastic leukemia (ALL) is much less common. CASE PRESENTATION: Herein, we describe an elderly man with PCM and a 14-year cumulative history of IMiD therapy who developed persistent pancytopenia and was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). He joins a group of 17 other patients documented in the literature who have followed a similar sequence of events starting with worsening cytopenias while on IMiD maintenance for PCM. These PCM patients were diagnosed with B-ALL after a median time of 36 months after starting IMiD therapy and at a median age of 61.5 years old. CONCLUSIONS: PCM patients with subsequent B-ALL have a poorer prognosis than their de novo B-ALL counterparts, however, the very low prevalence rate of subsequent B-ALL and high efficacy of IMiD maintenance therapy in PCM should not alter physicians' current practice. Instead, there should be a low threshold for bone marrow biopsy for unexplained cytopenias.


Assuntos
Lenalidomida/efeitos adversos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/etiologia , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia , Talidomida/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Medula Óssea , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Lenalidomida/uso terapêutico , Masculino , Talidomida/uso terapêutico
10.
Blood Adv ; 3(21): 3473-3480, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714964

RESUMO

Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto , Antígenos de Neoplasias/imunologia , Técnicas de Cultura de Células , Ensaios Clínicos como Assunto , Engenharia Genética , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Masculino , Mieloma Múltiplo/etiologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Resultado do Tratamento
11.
Cancer Radiother ; 23(8): 867-873, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31677902

RESUMO

PURPOSE: The primary objective was to determine in our department the progression-free survival rate of patients with solitary bone plasmocytoma and secondarily to evaluate its diagnostic, therapeutic and evolutionary aspects. PATIENTS AND METHODS: This is a retrospective review of 12 patients monitored and treated in the radiotherapy department of the Mohammed-V military medical teaching hospital in Rabat for a solitary bone plasmocytoma between January 2012 and December 2018. The average age of our patients were 53.8 years old (range: 31-72 years old). Pain was the most common telltale sign. The site of the lesions was spinal in four cases, iliac in four cases, mandibular, ribal, humeral and at the level of the astragalus in one case respectively. All patients received radiotherapy. This irradiation was delivered alone in 60% of cases or associated with surgery in 40% of cases. The average dose of radiotherapy was 47.3Gy (range: 45 to 50.4Gy) and this was delivered by a modulated volumetric arc therapy technique in ten patients and conformal tridimensional radiotherapy in two patients. RESULTS: Local control, defined by stability or radiological regression, was obtained in ten patients and four patients progressed to multiple myeloma, two of whom died. The average duration of follow-up was 51 months. CONCLUSION: Radiation therapy is the standard treatment for solitary bone plasmocytoma. It ensures good local control in 90% of cases. The prognosis is affected by progression to multiple myeloma, which justifies rigorous monitoring after treatment and suggests a reflection on the exact place of chemotherapy.


Assuntos
Neoplasias Ósseas/radioterapia , Plasmocitoma/radioterapia , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Progressão da Doença , Feminino , Hospitais Militares , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/mortalidade , Plasmocitoma/diagnóstico por imagem , Plasmocitoma/cirurgia , Prognóstico , Intervalo Livre de Progressão , Dosagem Radioterapêutica , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Estudos Retrospectivos
12.
Cancer Epidemiol Biomarkers Prev ; 28(12): 2055-2061, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31501149

RESUMO

BACKGROUND: Multiple myeloma is a common hematologic malignancy consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Little is known about postdiagnosis clinical predictors of progression of MGUS to multiple myeloma to guide MGUS management. This study aimed to investigate whether the rate of rise in serum monoclonal protein concentration during the year after MGUS diagnosis-M-protein velocity-predicts progression of MGUS to multiple myeloma. METHODS: Data from the U.S. Veterans Health Administration system were used. A retrospective cohort of patients with MGUS who progressed to multiple myeloma were matched on age at MGUS diagnosis and race in a 1:4 ratio to the patients with MGUS using incidence density sampling. Kaplan-Meier curves were plotted. Univariable and multivariable conditional logistic regression analyses were fitted from the matched risk sets. RESULTS: A total of 128 cases and 490 matched controls were included. The case group contained a higher percentage of patients with M-protein velocity >0.1 g/dL/year than the control group (44.5% vs. 28.2%, P <0.0001). M-protein velocity of >0.1 g/dL during the year following MGUS diagnosis was positively associated with progression of MGUS to multiple myeloma (multivariable-adjusted odds ratio = 2.15; 95% confidence interval, 1.37-3.35). CONCLUSIONS: Patients with a positive M-protein velocity during the year after MGUS diagnosis may be considered for more frequent monitoring for early detection and timely treatment of multiple myeloma. Future prevention studies could target these patients for intervention evaluation. IMPACT: Our results suggest a new clinical predictor of progression to multiple myeloma following MGUS diagnosis, which has potential to identify high-risk patients for management and prevention.


Assuntos
Biomarcadores Tumorais/sangue , Gamopatia Monoclonal de Significância Indeterminada/complicações , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Proteínas do Mieloma/análise , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Mieloma Múltiplo/etiologia , Prognóstico , Estudos Retrospectivos
14.
Cancer Immunol Res ; 7(8): 1224-1229, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31371317

RESUMO

Immune checkpoints and agonists modulate ongoing, antigen-specific immune responses. Therapeutic blockade of CTLA-4, PD-1, and PD-L1 has proven to be an effective treatment approach for a subset of patients with a variety of cancers of epithelial, mesenchymal, or hematologic origin. In multiple myeloma, a B-cell lymphoid malignancy of terminally differentiated plasma cells, PD-1 pathway blockade is ineffective as a single agent. The initial promise in combination approaches utilizing anti-PD-1 with the immunomodulatory drugs, lenalidomide or pomalidomide, was not confirmed in randomized trials. Here, we explore available data for and against manipulation of the PD-1 pathway and other immune checkpoints in myeloma and highlight several promising concepts and challenges that face ongoing development of immunotherapeutics for this disease.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Terapia de Alvo Molecular , Mieloma Múltiplo/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais , Antígeno CTLA-4/antagonistas & inibidores , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Avaliação Pré-Clínica de Medicamentos , Humanos , Imunomodulação/efeitos dos fármacos , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento
15.
J Cancer Res Clin Oncol ; 145(10): 2445-2455, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407112

RESUMO

PURPOSE: The 7th Heidelberg Myeloma Workshop was held on April 5th and 6th, 2019 at the University Hospital Heidelberg. METHODS AND RESULTS: Main topics of the meeting were (1) diagnostics and prognostic factors, (2) role of immunotherapy in multiple myeloma (MM), (3) current therapy of MM, (4) biology and genomics of MM as well as (5) novel treatment concepts. A debate on the status of minimal residual disease (MRD) driven therapy was held. CONCLUSION: Diagnostics and treatment of newly diagnosed and relapsed MM are continuously evolving. While advances in the field of (single cell) genetic analysis now allow for characterization of the disease at an unprecedented resolution, immunotherapeutic approaches and MRD testing are at the forefront of the current clinical trial landscape.


Assuntos
Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Gerenciamento Clínico , Humanos , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/mortalidade
16.
Stud Health Technol Inform ; 264: 98-102, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437893

RESUMO

With the growing interdisciplinarity of cancer treatment and increasing amounts of data and patients, it is getting increasingly difficult for physicians to capture a patient's medical history as a basis for adequate treatment and to compare different medical histories of similar patients to each other. Furthermore, in order to tackle the etiological mechanisms of cancer, it is crucial to identify patients exhibiting a different disease course than their corresponding cohort. Several timeline visualizations have already been proposed. However, the functions and design of such visualizations are always use case dependent. We constructed a cohort timeline prototype mock-up for a specific oncological use case involving multiple myeloma, where the chronological monitoring of various parameters is crucial for patient diagnosis and treatment. Our proposed cohort timeline is a synthesis between elements described in the literature and our own approaches regarding function and design.


Assuntos
Visualização de Dados , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/etiologia
17.
Blood Adv ; 3(13): 2040-2044, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289031

RESUMO

Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD+ Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry-based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD- patients relative to the 18 MRD+ patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD- and MRD+ patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.


Assuntos
Microbioma Gastrointestinal , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/etiologia , Neoplasia Residual/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Medula Óssea/patologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias , Resultado do Tratamento
18.
Hematol Oncol ; 37 Suppl 1: 62-65, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187526

RESUMO

The treatment of myeloma is rapidly evolving. This article reviews the current diagnostic criteria, risk stratification, and approach to treatment of multiple myeloma. Treatment approach for both newly diagnosed and relapsed disease are discussed.


Assuntos
Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Tomada de Decisão Clínica , Terapia Combinada , Gerenciamento Clínico , Humanos , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/mortalidade , Recidiva , Retratamento , Resultado do Tratamento
19.
Neoplasia ; 21(8): 777-787, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31247457

RESUMO

Multiple myeloma is a fatal plasma cell malignancy that is reliant on the bone marrow microenvironment. The bone marrow is comprised of numerous cells of mesenchymal and hemopoietic origin. Of these, macrophages have been implicated to play a role in myeloma disease progression, angiogenesis, and drug resistance; however, the role of macrophages in myeloma disease establishment remains unknown. In this study, the antimyeloma efficacy of clodronate-liposome treatment, which globally and transiently depletes macrophages, was evaluated in the well-established C57BL/KaLwRijHsd murine model of myeloma. Our studies show, for the first time, that clodronate-liposome pretreatment abrogates myeloma tumor development in vivo. Clodronate-liposome administration resulted in depletion of CD169+ bone marrow-resident macrophages. Flow cytometric analysis revealed that clodronate-liposome pretreatment impaired myeloma plasma cell homing and retention within the bone marrow 24 hours postmyeloma plasma cell inoculation. This was attributed in part to decreased levels of macrophage-derived insulin-like growth factor 1. Moreover, a single dose of clodronate-liposome led to a significant reduction in myeloma tumor burden in KaLwRij mice with established disease. Collectively, these findings support a role for CD169-expressing bone marrow-resident macrophages in myeloma disease establishment and progression and demonstrate the potential of targeting macrophages as a therapy for myeloma patients.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Ácido Clodrônico/administração & dosagem , Suscetibilidade a Doenças , Lipossomos , Macrófagos/imunologia , Macrófagos/metabolismo , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/metabolismo , Animais , Biomarcadores , Contagem de Células , Linhagem Celular Tumoral , Movimento Celular , Modelos Animais de Doenças , Imunofenotipagem , Camundongos , Mieloma Múltiplo/patologia , Osteoblastos , Microambiente Tumoral
20.
Intern Med ; 58(19): 2845-2849, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243219

RESUMO

A 75-year-old Japanese woman with a 20-year history of rheumatoid arthritis presented with symptomatic bilateral pleural effusion and lung and brain tumors. She had received methotrexate for five years and tacrolimus for one year. A brain biopsy specimen showed the pathological features of lymphoproliferative disease, but a bone marrow biopsy showed proliferation of plasma cells. She was finally diagnosed with coexistent lymphomatoid granulomatosis (LYG) of the brain and lung and multiple myeloma (MM) of the bone marrow and received chemotherapy for both. This report shows that immunodeficient patients are at risk of developing the unusual coexistence of LYG and MM.


Assuntos
Artrite Reumatoide/complicações , Neoplasias Encefálicas/etiologia , Síndromes de Imunodeficiência/complicações , Neoplasias Pulmonares/etiologia , Granulomatose Linfomatoide/etiologia , Mieloma Múltiplo/etiologia , Idoso , Biópsia , Neoplasias Encefálicas/diagnóstico , Evolução Fatal , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Granulomatose Linfomatoide/diagnóstico , Imagem por Ressonância Magnética , Mieloma Múltiplo/tratamento farmacológico , Tomografia Computadorizada por Raios X
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