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3.
Lancet Haematol ; 7(10): e737-e745, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32798473

RESUMO

BACKGROUND: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. METHODS: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing. FINDINGS: We enrolled 536 patients with a median follow-up of 20 days (IQR 10-34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77-2·34) in our whole study cohort and 3·72 (2·86-4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1-44·9). Older age (hazard ratio 1·03, 95% CI 1·01-1·05); progressive disease status (2·10, 1·41-3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56-7·81), indolent non-Hodgin lymphoma (2·19, 1·07-4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34-4·89), or plasma cell neoplasms (2·48, 1·31-4·69), and severe or critical COVID-19 (4·08, 2·73-6·09) were associated with worse overall survival. INTERPRETATION: This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available. FUNDING: Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Neoplasias Hematológicas/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Feminino , Seguimentos , Neoplasias Hematológicas/terapia , Humanos , Pacientes Internados , Itália/epidemiologia , Leucemia/epidemiologia , Leucemia/terapia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/terapia , Neoplasias de Plasmócitos/epidemiologia , Neoplasias de Plasmócitos/terapia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Ann Diagn Pathol ; 44: 151449, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865247

RESUMO

The characteristics of the IgA plasma cell neoplasms are not clearly reported in the literature. The main goal of this study is to examine IgA plasma cell neoplasms (PCN) and to compare them to IgG lesions. After at least 5 years from the identification of an M protein, 98 cases were selected, the presentation and clinical evolution of 45 IgA neoplasms were compared to 43 cases of IgG gammopathies. The classification at presentation as monoclonal gammopathy of undermined significance (MGUS)-22 of 45 IgA and 20 of 43 IgG (49 vs 46%), plasma cell myeloma (PCM)-22 of 45 IgA and 22 of 43 IgG (49 vs 51%) and smoldering PCM (SPCM)-1 each (2% for both) was essentially identical. No solitary plasmacytomas were identified. At presentation, IgA patients were younger (66.5 ± 11.3 vs. 69.2 ± 10.7 years), less likely to have bone lesions (12/45 vs 18/43, p < 0.14) or immunoparesis (51% vs. 63%), differences statistically insignificant. Cases with normal fluorescence in-situ hybridization (FISH) results, 27% for IgA vs 61% for IgG (p < 0.037) were statistically different. The IgA patients had worse survival (80 vs 108 months median IgA vs IgG, p < 0.013), difference not detectable in the first 5 years, but substantial after 10. In conclusion, poorer long-term survival and increased genomic complexity by FISH are characteristics of IgA PCNs.


Assuntos
Imunoglobulina A , Imunoglobulina G , Neoplasias de Plasmócitos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada , Neoplasias de Plasmócitos/genética , Neoplasias de Plasmócitos/imunologia , Neoplasias de Plasmócitos/mortalidade , Estudos Retrospectivos
6.
Digestion ; 101(2): 198-207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30904916

RESUMO

BACKGROUND AND OBJECTIVES: Allogenic hematopoietic stem cell transplantation (allo-SCT) is a curative therapy for hematological malignancies, but transplant-related mortality (TRM) remains a concern. This study aimed to determine the efficacy of capsule endoscopy (CE) by evaluating the correlation between inflammatory findings on CE and TRM. METHODS: The data of patients after allo-SCT were retrospectively collected. The association between findings on CE and TRM at 100 days from the CE was evaluated. RESULTS: Of the 94 patients included in the study, 47 showed inflammatory findings on CE. The findings were diagnosed as graft-versus-host disease (GVHD; n = 17), cytomegalovirus (CMV) infection (n = 14), and GVHD with CMV infection (n = 16). Of the 47 patients, 13 (28%) had TRM. Endoscopic diagnoses of these TRM cases were GVHD (n = 4), CMV infection (n = 0), and GVHD with CMV infection (n = 9). In contrast, in the remaining 47 patients who showed no inflammatory findings on CE, 2 patients (4%) had TRM. The proportion of TRM was higher in patients with inflammatory findings than in those without it (28 vs. 4%, p < 0.01). CONCLUSIONS: CE may predict TRM in patients who developed gastrointestinal symptoms after allo-SCT.


Assuntos
Endoscopia por Cápsula/estatística & dados numéricos , Infecções por Citomegalovirus/mortalidade , Gastroenteropatias/mortalidade , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Adolescente , Adulto , Idoso , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia/terapia , Linfoma/terapia , Pessoa de Meia-Idade , Neoplasias de Plasmócitos/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem
7.
Rev Med Chil ; 147(8): 1036-1041, 2019 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-31859969

RESUMO

Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte neoplasms, lymphogenesis should be well known. We must keep in mind that the last stage of maturation of these lymphocytes is the plasma cell. This is how a MG could appear in the context of a plasma cell neoplasm, such as multiple myeloma or amyloidosis, but also in relation to a lymphoma. A monoclonal peak is produced by mature B lymphocytes or plasma cells that secrete a monoclonal protein (Immunoglobulin), and represents a MG. But it must be emphasized that, in the correct clinical context, a hypogammaglobulinemia can represent a MG as well. Another important point is the understanding and interpretation of requested tests, such as protein electrophoresis (PEP), immunofixation (IFx) or serum free light chains (sFLC). The current MG screening panel includes these three studies (PEF, IFx, sFLC), although a simpler panel measuring PEF and sFLC has also been proposed, but not yet formally validated. Therefore, screening done only with PEP is insufficient.


Assuntos
Neoplasias de Plasmócitos/sangue , Paraproteinemias/sangue , Paraproteínas/análise , Linfócitos B/metabolismo , Eletroforese das Proteínas Sanguíneas/métodos , Humanos , Neoplasias de Plasmócitos/diagnóstico , Paraproteinemias/diagnóstico
9.
Cytometry B Clin Cytom ; 96(5): 338-350, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31566910

RESUMO

This review focuses on the roles of flow cytometric immunophenotyping has in the differential diagnosis of plasma cell neoplasms and the post-therapy monitoring of minimal (measurable) residual disease. The need to integrate flow cytometry data with clinical, laboratory, radiographic, morphological, and molecular genetic findings is emphasized. The challenges of and strategies for evaluating plasma cells in the setting of targeted therapy are also highlighted. © 2019 International Clinical Cytometry Society.


Assuntos
Citometria de Fluxo , Imunofenotipagem , Neoplasias de Plasmócitos/diagnóstico , Humanos
10.
Rev. méd. Chile ; 147(8): 1036-1041, ago. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1058640

RESUMO

Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte neoplasms, lymphogenesis should be well known. We must keep in mind that the last stage of maturation of these lymphocytes is the plasma cell. This is how a MG could appear in the context of a plasma cell neoplasm, such as multiple myeloma or amyloidosis, but also in relation to a lymphoma. A monoclonal peak is produced by mature B lymphocytes or plasma cells that secrete a monoclonal protein (Immunoglobulin), and represents a MG. But it must be emphasized that, in the correct clinical context, a hypogammaglobulinemia can represent a MG as well. Another important point is the understanding and interpretation of requested tests, such as protein electrophoresis (PEP), immunofixation (IFx) or serum free light chains (sFLC). The current MG screening panel includes these three studies (PEF, IFx, sFLC), although a simpler panel measuring PEF and sFLC has also been proposed, but not yet formally validated. Therefore, screening done only with PEP is insufficient.


Assuntos
Humanos , Paraproteinemias/sangue , Paraproteínas/análise , Neoplasias de Plasmócitos/sangue , Paraproteinemias/diagnóstico , Eletroforese das Proteínas Sanguíneas/métodos , Linfócitos B/metabolismo , Neoplasias de Plasmócitos/diagnóstico
12.
Surg Pathol Clin ; 12(3): 745-770, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352986

RESUMO

Although about 90% of the world's population is infected by EBV only a small subset of the related infections result in neoplastic transformation. EBV is a versatile oncogenic agent involved in a multitude of hematopoietic, epithelial, and mesenchymal neoplasms, but the precise role of EBV in the pathogenesis of many of the associated lymphoid/histiocytic proliferations remains hypothetical or not completely understood. Additional studies and use of evolving technologies such as high-throughput next-generation sequencing may help address this knowledge gap and may lead to enhanced diagnostic assessment and the development of potential therapeutic interventions.


Assuntos
Infecções por Vírus Epstein-Barr/classificação , Transtornos Linfoproliferativos/classificação , Animais , Doença Crônica , Culicidae , Diagnóstico Diferencial , Humanos , Hidroa Vaciniforme/diagnóstico , Imunossupressores/efeitos adversos , Mononucleose Infecciosa/diagnóstico , Mordeduras e Picadas de Insetos/diagnóstico , Linfoma de Células B/classificação , Linfoma de Células B/virologia , Linfoma de Células T/classificação , Linfoma de Células T/virologia , Granulomatose Linfomatoide/diagnóstico , Transtornos Linfoproliferativos/virologia , Neoplasias de Plasmócitos/diagnóstico , Prognóstico , Pseudolinfoma/diagnóstico , Pseudolinfoma/virologia , Latência Viral/fisiologia
13.
Eur Rev Med Pharmacol Sci ; 23(10): 4293-4302, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31173301

RESUMO

OBJECTIVE: Monoclonal plasma cell proliferative disorders comprise a wide spectrum of diseases associated to clonal B-cell expansion. Serum protein electrophoretic profile (SPEP) and circulating free light chains (FLCs) levels are the mainstay of diseases management. Recently, soluble (s) Syndecan-1 (SDC1, CD138) produced by myeloma plasma cells has been suggested in the monitoring and follow-up of patients with myeloma. The aim of our study is to evaluate sCD138 in addition with FLCs and SPEP for the screening of patients with different evolutive disease pathways. PATIENTS AND METHODS: Sera from 73 patients with monoclonal gammopathy of undetermined significance (MGUS), 120 smoldering and 42 multiple myeloma (SMM and MM, respectively), 70 HCV-related mixed cryoglobulinemia (MC), 35 B-cell non-Hodgkin's lymphoma (B-NHL) and sera from 50 healthy donors (HD), were tested for sCD138, FLCs (assessed by means of ELISA and turbidimetric assay, respectively) and electrophoresis pattern (performed on Capillarys system) for the generation of a novel biomarker score (BS). RESULTS: Our results were grouped according to the two main lines of disease progression (vs. MM or B-NHL): in one group we found BS mean values of 0.2, 3.4, 5.3, 7.1 for HD, MGUS, SMM and MM, respectively; in the other group of 0.2, 4.4, 6.7 for HD, MC and B-NHL. CONCLUSIONS: We showed that BS mean values follow the ingravescence disease status towards the two main lines of progression to cancerous conditions; it could represent an additional useful tool in the management of screening and/or follow-up.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/terapia , Sindecana-1/sangue , Adulto , Eletroforese das Proteínas Sanguíneas , Progressão da Doença , Feminino , Humanos , Masculino , Programas de Rastreamento , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo/sangue , Neoplasias de Plasmócitos/sangue , Nefelometria e Turbidimetria/métodos , Paraproteinemias/sangue , Valor Preditivo dos Testes , Prognóstico
14.
BMC Ophthalmol ; 19(1): 110, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088416

RESUMO

BACKGROUND: The purpose of this case series was to further characterize proteasome inhibitor associated chalazia and blepharitis, to investigate outcomes of different management strategies, and to propose a treatment algorithm for eyelid complications in this patient population. METHODS: This retrospective case series included sixteen patients found to have chalazia and/or blepharitis while receiving proteasome inhibitors for plasma cell disorders at Mount Sinai Hospital in New York, NY from January 2010 through January 2017. Main outcomes were complete resolution of eyelid complications and time to resolution. Student's t-test was used to compare average values and Fisher's exact test was used to compare proportions. RESULTS: Fourteen patients had chalazia and 10 had blepharitis. Chalazia averaged 5.4 mm, and 11 patients with chalazia experienced two or more lesions. Median follow-up time was 17 months. Average time from bortezomib exposure to onset of first eyelid complication was 3.4 months. Chalazia episodes were more likely to completely resolve than blepharitis episodes (p = 0.03). Ocular therapy alone was trialed for an average of 1.8 months before proceeding to bortezomib omission. Average time to eyelid complication resolution using ocular therapy alone was 1.8 months versus 3.1 months after bortezomib omission. In this series, the combination of ocular therapy and bortezomib omission led to complete resolution of eyelid complications more often than ocular therapy alone. CONCLUSION: Proteasome inhibitor associated eyelid complications were identified in sixteen patients with plasma cell disorders. Eyelid complications may be treated with a 2-month trial of conservative ocular therapies alone, followed by continuation of ocular therapy in combination with bortezomib omission if eyelid signs persist.


Assuntos
Blefarite/induzido quimicamente , Bortezomib/efeitos adversos , Calázio/induzido quimicamente , Inibidores de Proteassoma/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Plasmócitos/tratamento farmacológico , Estudos Retrospectivos
17.
BMJ Case Rep ; 12(3)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30846451

RESUMO

Extramedullaryplasmacytoma (EMP) represents a peculiar and typically progressive malignancy that can originate outside the bone marrow. Primary pulmonary plasmacytoma (PPP) is a rare subset of EMP, confined to the lung. A 55-year-old man, diabetic, non-smoker presented to our clinic with a right chest wall swelling. A routine chest radiograph showed a well-circumscribed opacity in the right upper lung zone. A CT of the chest revealed a large right upper lobe mass with extensive local infiltration. Biopsy and immunohistochemical evaluation led to a diagnosis of PPP. Screening for multiple myeloma was negative. Serum immunofixation showed an IgG lambda monoclonal gammopathy, found in a minority of PPP patients. In view of disease extent, treatment with chemotherapy and radiotherapy was initiated. The patient is currently in out patient follow-up and has shown a favourable response to the treatment with a considerable decrease in serum IgG levels.


Assuntos
Neoplasias Pulmonares/patologia , Neoplasias de Plasmócitos/patologia , Paraproteinemias/patologia , Plasmocitoma/patologia , Assistência ao Convalescente , Quimiorradioterapia/métodos , Humanos , Imunoglobulina G/sangue , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/imunologia , Paraproteinemias/sangue , Paraproteinemias/imunologia , Plasmocitoma/tratamento farmacológico , Plasmocitoma/metabolismo , Plasmocitoma/radioterapia , Doenças Raras , Resultado do Tratamento
18.
Exp Hematol ; 73: 13-17.e2, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30825517

RESUMO

Dysmegakaryopoiesis is a diagnostic criterion for myelodysplastic syndrome (MDS), which accompanies thrombocytopenia. Recently, dysmegakaryopoiesis was reported in patients with plasma cell neoplasm (PCN). Although these patients maintained normal platelet counts, disease progressed, with most bone marrow cells being replaced by plasma cells. Several studies reported that dysmegakaryopoiesis was induced by inflammatory mechanisms; however, the exact mechanism underlying dysmegakaryopoiesis remains unknown. This study aimed to investigate whether changes in the megakaryocytic expression of GATA-1, pro-inflammatory cytokines (interleukin [IL]-6 and IL-8), and CD9 affect platelet counts and dysmegakaryopoiesis in patients with PCN and MDS. A total 114 patients were examined and categorized into four groups: MDS with dysmegakaryopoiesis (34 patients), PCN without dysmegakaryopoiesis (36 patients), PCN with dysmegakaryopoiesis (19 patients), and lymphoma without bone marrow infiltration (25 patients). Expression of GATA-1, IL-6, IL-8, and CD9 in megakaryocytes was assessed by immunohistochemical (IHC) staining of paraffin-embedded bone marrow sections. Localized expression of transcription factor and cytokines was observed in megakaryocytes. Furthermore, expression of GATA-1, IL-6, and IL-8 significantly differed (all p values < 0.05). Decreased GATA-1 expression was identified in MDS. Decreased IL-6 expression was observed in PCN and MDS. Moreover, decreased IL-8 expression was associated with dysmegakaryopoiesis, regardless of whether platelet counts were maintained. In conclusion, PCN patients with dysmegakaryopoiesis had normal platelet counts, and their megakaryocytes showed decreased IL-6 and IL-8 expression and normal GATA-1 expression. The differences in the megakaryocytic expression of cytokines in PCN and MDS with dysmegakaryopoiesis may be applicable to future therapeutic strategies.


Assuntos
Fator de Transcrição GATA1/sangue , Regulação Neoplásica da Expressão Gênica , Interleucina-6/sangue , Interleucina-8/sangue , Megacariócitos/metabolismo , Proteínas de Neoplasias/sangue , Neoplasias de Plasmócitos/sangue , Trombopoese , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Megacariócitos/patologia , Pessoa de Meia-Idade , Neoplasias de Plasmócitos/patologia , Contagem de Plaquetas
20.
Int J Mol Sci ; 20(3)2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30678047

RESUMO

Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes tumor angiogenesis, proliferation, invasion, and metastasis, and also mediates mechanisms of therapeutic resistance. An increased number of mast cells has been demonstrated in angiogenesis associated with hematological tumors. In this review we focused on the role of mast cells in angiogenesis in human plasma cell malignancies. In this context, mast cells might act as a new target for the adjuvant treatment of these tumors through the selective inhibition of angiogenesis, tissue remodeling and tumor-promoting molecules, permitting the secretion of cytotoxic cytokines and preventing mast cell-mediated immune suppression.


Assuntos
Mastócitos/imunologia , Mastócitos/metabolismo , Neoplasias de Plasmócitos/etiologia , Neoplasias de Plasmócitos/metabolismo , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Animais , Biomarcadores , Medula Óssea/metabolismo , Medula Óssea/patologia , Contagem de Células , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/metabolismo , Suscetibilidade a Doenças , Humanos , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Neoplasias de Plasmócitos/patologia , Neoplasias de Plasmócitos/terapia , Plasmocitoma/etiologia , Plasmocitoma/metabolismo , Plasmocitoma/patologia , Microambiente Tumoral
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