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1.
Ann Hematol ; 99(2): 229-239, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31907572

RESUMO

The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Two-year progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3-41.9) vs 63.9% (95% CI 5.1-72.7), p < 0.001]. Two-year overall survival (OS) was 40.6% (95% CI 28.1-53.1) and 77.7% (95% CI 70.1-85.3) in the hypercalcemia and control cohorts, respectively (p < 0.001). Hypercalcemia was independently associated with poor PFS [HR = 2.5 (95% CI 1.4-3.5)] and OS [HR = 4.7 (95% CI 2.8-7.8)] in multivariate analysis. Among the 40 patients who received autologous stem cell transplantation (ASCT), hypercalcemia was still associated with shorter OS [2-year OS: 65% (95% CI 40.1-89.9) vs 88.0 (95% CI 75.3-100), p = 0.04]. Hypercalcemia may be associated with chemo-resistance, given its impact on PFS and OS. Hence, these data suggest that alternate strategies for lymphoma patients with hypercalcemia should be developed.


Assuntos
Hipercalcemia , Linfoma Difuso de Grandes Células B , Transplante de Células-Tronco , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/diagnóstico , Hipercalcemia/mortalidade , Hipercalcemia/terapia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
2.
Anticancer Res ; 39(9): 4925-4931, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519597

RESUMO

BACKGROUND/AIM: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy where antioxidant enzyme peroxiredoxin 6 (Prx6) has previously been associated with adverse outcomes. Its systemic effects in DLBCL are unknown. MATERIALS AND METHODS: This study included 53 patients with DLBCL, five patients with primary central nervous system lymphoma (PCNSL) and 20 healthy controls. The expression of Prx6 was evaluated immunohistochemically in DLBCL tissue samples and compared to its expression in blood serum. RESULTS: Prx6 expression was the highest in healthy controls, followed by DLBCL patients and PCNSL patients. Febrile neutropenic infection after the first treatment course was associated with low pre-treatment Prx6 serum levels (<14 ng/ml) (p=0.025, OR=8.615, 95% confidence interval=1.032-71.933). Serum levels of Prx6 recovered after treatment (p=0.006). CONCLUSION: Patients with low Prx6 levels might be more prone to treatment-related adverse effects through elevated levels of oxidative stress.


Assuntos
/etiologia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/complicações , Neutropenia/complicações , Neutropenia/etiologia , Peroxirredoxina VI/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medição de Risco , Fatores de Risco
3.
Int J Immunopathol Pharmacol ; 33: 2058738419863217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280618

RESUMO

Primary prostate lymphoma (PPL) is rare. This article reports a case of PPL by retrospective analysis of the clinical data and review of the literature, in an attempt to explore the diagnosis, treatment, and prognosis of this rare disease. The present case involves a male patient who came to our hospital for medical consultation of dysuria. Serum prostate-specific antigen (PSA) was not remarkable. Pelvic computed tomography (CT) scan suggested obvious enlargement of the prostate and a tumor in the prostate, but the tumor was not significantly enhanced on contrast-enhanced CT scan. Ultrasound suggested obvious enlargement of the prostate with multiple local low-density echoes and rich blood flow signals inside. Histopathology of prostate biopsy suggested prostate diffuse large B-cell lymphoma (DLBCL). The patient refused chemotherapy but agreed to receive radiotherapy. After radiotherapy, the tumor became smaller and the International Prostate Symptom Score (IPSS) score was reduced. Our experience, together with literature review, suggests that prostate puncture biopsy is an important method for the diagnosis of PPL, and imaging examination can assist the diagnosis. Radiotherapy is able to reduce the tumor volume and relieve the symptoms of urinary tract obstruction, and chemotherapy can help achieve a better therapeutic outcome.


Assuntos
Linfoma/diagnóstico , Linfoma/patologia , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Idoso de 80 Anos ou mais , Biópsia/métodos , Humanos , Linfoma/sangue , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Estudos Retrospectivos
4.
Hematology ; 24(1): 544-551, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31315540

RESUMO

Objective: Immunoglobulin D (IgD) levels are often elevated in patients with autoimmune diseases. However, the oncogenic activities of IgD and IgD receptor (IgDR) in diffuse large B-cell lymphoma (DLBCL) have not been reported in detail. Therefore, we aimed to investigate the expression of IgD and IgDR in patients with DLBCL. Methods: Membrane IgD (mIgD) and IgDR expression in tissue samples was analyzed using IHC, mIgD and IgDR expression on peripheral blood mononuclear cells (PBMCs) was analyzed by FCM, and secreted IgD (sIgD) level was analyzed by ELISA. Fisher's exact test and Spearman correlation analysis were used to evaluate the relationship between IgD, IgDR, and clinical parameters. Results: The pathological lymph nodes of 34 patients with DLBCL were studied, and mIgD and IgDR expression was found in 16 and 19 patients. mIgD and IgDR expression was upregulated in patients with DLBCL and mIgD expression was significantly associated with IgDR expression. Further correlation analysis showed that mIgD expression was correlated with serum ß2-MG level and Hans algorithm as germinal center B (GCB), whereas IgDR expression correlated with serum LDH level, IPI score and GCB. ELISA showed that sIgD level was significantly increased in DLBCL patients and it correlated with serum ß2-MG and LDH levels. FCM showed that mIgD and IgDR expression in PBMCs of patients with DLBCL was significantly higher than that in healthy controls. Conclusion: Our findings suggest that overexpression of IgD and IgDR is an abnormal activation state in DLBCL.


Assuntos
Regulação Neoplásica da Expressão Gênica , Imunoglobulina D/biossíntese , Leucócitos Mononucleares/química , Receptores Fc/biossíntese , Estudos de Casos e Controles , Linhagem Celular Tumoral , Membrana Celular/imunologia , Feminino , Humanos , Imunoglobulina D/análise , Imunoglobulina D/genética , L-Lactato Desidrogenase/sangue , Linfonodos/química , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pseudolinfoma/sangue , Pseudolinfoma/patologia , Receptores Fc/análise , Receptores Fc/genética , Regulação para Cima , Microglobulina beta-2/análise
5.
BMC Cancer ; 19(1): 553, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31176361

RESUMO

BACKGROUND: Liver function is routinely assessed in clinical practice as liver function tests provide sensitive indicators of hepatocellular injury. However, the prognostic value of enzymes that indicate hepatic injury has never been systematically investigated in lymphoma, including diffuse large B-cell lymphoma (DLBCL). METHODS: This study examined the prognostic value of baseline aspartic transaminase (AST) in DLBCL patients. The association between AST and clinical features was analyzed in 179 DLBCL patients treated from 2006 to 2016. All enrolled patients were treated with R-CHOP or R-CHOP-like chemotherapy. Log-rank test, univariable analysis, and subgroup analysis were performed to evaluate the impact of AST on survival. RESULTS: AST 33.3 U/L was considered to be the optimal threshold value for predicting prognosis. A higher AST level was associated with advanced stage (P = 0.001), poorer performance status (P = 0.014), elevated lactate dehydrogenase level (P <  0.0001), presence of B symptoms (P = 0.001), high-risk International Prognostic Index (IPI, IPI 3-5) (P = 0.002), non-germinal center B-cell subtypes (P = 0.038), hepatitis B virus surface antigen positivity (P = 0.045) and more extra nodal involvement (ENI, ENI ≥ 2) (P = 0.027). Patients with a higher AST level had a shorter overall survival (OS) (2-year OS rate, 53.6% vs. 83.6%, P <  0.001). Subgroup analysis indicated that higher AST levels have poorer prognostic values in patients without B symptoms and LDH positive groups. CONCLUSION: A pretreatment AST level is associated with OS in DLBCL patients treated with R-CHOP or similar chemotherapy regimens. A high pretreatment AST level might be a reliable prognostic factor for predicting a dismal outcome in DLBCL patients. Serum AST levels may be investigated for use as an easily determinable, inexpensive biomarker for risk assessment in patients with DLBCL.


Assuntos
Aspartato Aminotransferases/sangue , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Terapia Combinada , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
6.
Crit Rev Oncol Hematol ; 139: 7-15, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112884

RESUMO

Cell-free DNA (cfDNA), which is DNA released from cells into the circulation, is one of the most promising non-invasive biomarkers in cancer. This approach could be of interest for the management of Diffuse Large B-Cell Lymphoma (DLBCL) patients, which is the most common non-Hodgkin lymphoma. Then, the aim of this systematic review was to define the utility of cfDNA in this disease. Selected articles were classified in four groups, depending on the aspects of cfDNA studied, i.e. concentration, methylation, IgH gene rearrangements, and somatic mutations. While concentration and methylation of cfDNA need to be further analyzed, IgH gene rearrangements and somatic mutations seem to be the most promising biomarkers to date. Their detection has been shown to allow disease monitoring and early prediction of relapse. Although more efforts and standardization of techniques are needed, studying cfDNA in liquid biopsy may help improve the outcome of DLBCL patients.


Assuntos
Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Ácidos Nucleicos Livres/sangue , Humanos , Biópsia Líquida , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/genética , Prognóstico
9.
Am J Hematol ; 94(5): 604-616, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30859597

RESUMO

DISEASE OVERVIEW: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma originating from the germinal center, and it represents a heterogeneous group of diseases with variable outcomes that are differentially characterized by clinical features, cell of origin (COO), molecular features, and most recently, frequently recurring mutations. DIAGNOSIS: DLBCL is ideally diagnosed from an excisional biopsy of a suspicious lymph node, which shows sheets of large cells that disrupt the underlying structural integrity of the follicle center and stain positive for pan-B-cell antigens, such as CD20 and CD79a. COO is determined by immunohistochemical stains, while molecular features such as double-hit or triple-hit disease are determined by fluorescent in situ hybridization analysis. Commercial tests for frequently recurring mutations are currently not routinely used to inform treatment. RISK STRATIFICATION: Clinical prognostic systems for DLBCL, including the rituximab International Prognostic Index, age-adjusted IPI, and NCCN-IPI, use clinical factors for the risk stratification of patients, although this does not affect the treatment approach. Furthermore, DLBCL patients with non-germinal center B-cell (GCB)-like DLBCL (activated B-cell like and unclassifiable) have a poorer response to up-front chemoimmunotherapy (CI) compared to patients with GCB-like DLBCL. Those with c-MYC-altered disease alone and in combination with translocations in BCL2 and/or BCL6 (particularly when the MYC translocation partner is immunoglobulin) respond poorly to up-front CI and salvage autologous stem cell transplant at relapse. RISK-ADAPTED THERAPY: This review will focus on differential treatment of DLBCL up-front and at the time of relapse by COO and molecular features.


Assuntos
Antígenos CD20/sangue , Antígenos de Neoplasias/sangue , Antígenos CD79/sangue , Linfoma Difuso de Grandes Células B , Proteínas de Neoplasias/sangue , Transplante de Células-Tronco , Autoenxertos , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Medição de Risco , Biópsia de Linfonodo Sentinela
10.
Swiss Med Wkly ; 149: w14709, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30673117

RESUMO

In the era of personalised medicine, genetic information is critical to directing therapeutic options, aiding risk stratification and disease monitoring of lymphomas. Liquid biopsy is a novel noninvasive, real-time and tumour-specific technique, reliably reflecting the comprehensive tumour genetic profile, and thus holds great promise for the genetic assessment, response monitoring and relapse detection of lymphomas. Standard methods for disease response assessment in patients with lymphoma, including positron emission tomography, are imperfect. In other haematological malignancies, particularly leukaemias, the ability to detect minimal residual disease (MRD) is increasingly influencing treatment paradigms. However, in some subtypes of lymphoma, such as diffuse large B-cell lymphoma and classic Hodgkin’s lymphoma, the application of MRD assessment techniques such as flow cytometry or polymerase chain reaction-based methods has been challenged by the absence of circulating disease. The review summarises the applications of liquid biopsy in the assessment of tumour burden and response to therapy, noninvasive genomic profiling, and monitoring of clonal dynamics in patients with diffuse large B-cell lymphoma and classic Hodgkin’s lymphoma.


Assuntos
Doença de Hodgkin/patologia , Biópsia Líquida/métodos , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/patologia , Biomarcadores Tumorais/sangue , Técnicas de Genotipagem , Doença de Hodgkin/sangue , Doença de Hodgkin/genética , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/genética , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Neoplasia Residual/sangue , Neoplasia Residual/genética
11.
J Infect Chemother ; 25(5): 404-406, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30685110

RESUMO

Blood cultures are the most valuable tool when bacteremia is clinically suspected. Technical advances have led to the development of automated blood culture systems to detect bacterial infections. Usually positive signals in automated blood culture systems result from the proliferation of microorganisms. Cases are classified as false-positive when the automated blood culture system produces a positive signal but no microorganisms are detected on Gram-stained smears and no microorganism growth is observed in blood subcultures. False-positive blood culture results are very rare in patients with hematologic malignancies. Recently, we encountered four patients who had false-positive blood culture results. Two of the patients were diagnosed with acute leukemia, involving hyperleukocytosis and an excess of blasts. The other two patients were diagnosed with acute leukemia and diffuse large B cell lymphoma with leukocytopenia. Although hypercapnia or acidosis, apart from hyperleukocytosis, might also cause false-positive results, our cases clearly did not have these conditions. We should be aware of the possibility that false-positive blood culture results can occur in patients with leukocytopenia, as well as hyperleukocytosis. To understand the mechanisms responsible for the observed false-positive results, additional studies are needed after the accumulation of similar cases.


Assuntos
Bacteriemia/diagnóstico , Técnicas Bacteriológicas/métodos , Hemocultura/métodos , Leucemia Mieloide Aguda/sangue , Linfoma Difuso de Grandes Células B/sangue , Adulto , Idoso , Automação Laboratorial , Bacteriemia/microbiologia , Hemocultura/instrumentação , Reações Falso-Positivas , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Linfoma Difuso de Grandes Células B/complicações , Masculino
12.
Acta Clin Belg ; 74(5): 359-363, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30238855

RESUMO

Objectives: Since primary intestinal aspergillosis is a severe infectious complication with a high morbidity and mortality in immunocompromised patients, we want to draw attention to this rare entity and the importance of early recognition. Methods: We report a case of documented primary intestinal aspergillosis in a patient receiving an autologous stem cell transplantation (SCT). Furthermore, this article gives a short reflection on the occurrence of invasive aspergillosis in autologous SCT and the value of serum galactomannan levels based on literature search and linked with the case. Results: In this case the patient presented on day +8 after autologous SCT for a relapsed diffuse large B-cell lymphoma with an acute abdomen with urgent need for surgical intervention. Biopsy revealed the presence of fungal colonies due to aspergillosis and voriconazole was started. Until that day the systematically taken serum galactomannan tests were all negative or pending. Initially there was some resistance to perform surgery in the presence of neutropenia and thrombocytopenia but in the end it provided the definitive diagnosis and should not be delayed. Until now this patient is in good health and retains a complete remission. Conclusion: With this case, we would like to emphasize that early recognition of primary intestinal aspergillosis is of the utmost importance as it is a rare but serious infectious complication. It should be included in the differential diagnosis of neutropenic patients with sudden onset abdominal pain and ongoing fever, even in the absence of a positive serum galactomannan.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Volvo Intestinal/cirurgia , Linfoma Difuso de Grandes Células B/terapia , Neoplasias Nasofaríngeas/terapia , Recidiva Local de Neoplasia/terapia , Aspergilose/sangue , Aspergilose/complicações , Aspergilose/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Volvo Intestinal/sangue , Volvo Intestinal/etiologia , Linfoma Difuso de Grandes Células B/sangue , Masculino , Mananas/sangue , Neoplasias Nasofaríngeas/sangue , Transplante Autólogo , Adulto Jovem
13.
Ann Hematol ; 98(2): 413-422, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30374624

RESUMO

Aberrant monocyte chemoattractant protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) expression in malignant tissues have been reported; however, their role in hematological malignancies prognosis remains little known. The aim of this study was to investigate the prognostic value of MCP-1 and CCR2 expression in patients with diffuse large B cell lymphoma (DLBCL). The study included 221 patients with DLBCL. MCP-1 and CCR2 expression was analyzed by immunohistochemical staining and its correlations with clinicopathologic features and prognosis were evaluated. High expression of MCP-1 or CCR2 was correlated with clinicopathological characteristics, and an adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) of DLBCL patients. Also, significant positive correlation between MCP-1 and CCR2 expression was revealed (r = 0.545, P < 0.001). Patients with high MCP-1 or high CCR2 expression had significantly poorer OS and PFS than those with low MCP-1 or low CCR2 expression (OS: P < 0.001, P < 0.001; PFS: P < 0.001, P < 0.001), respectively, even in the rituximab era, and MCP-1 or CCR2 expression could further identify high-risk patients otherwise classified as low/intermediate risk by the International Prognostic Index (IPI) alone. Furthermore, incorporation of MCP-1 or CCR2 expression into the IPI score could improve prognostic value for OS. This is the first report describing the clinicopathological features and survival outcome according to expression of MCP-1 and CCR2 in DLBCL.


Assuntos
Quimiocina CCL2/sangue , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B , Proteínas de Neoplasias/sangue , Receptores CCR2/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
14.
Ann Hematol ; 98(2): 391-399, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30377764

RESUMO

The prognostic value of tumour-infiltrating T lymphocytes (TIL-Ts) has been demonstrated in many solid tumours but remained unclear in diffuse large B cell lymphoma (DLBCL). We conducted a retrospective cohort study reviewing the TIL-Ts proportion and CD4:CD8 of 66 de novo DLBCL by flow cytometry to construct a risk stratification based on TIL-Ts-related prognostic factors. In univariate analysis, low TIL-Ts (< 14%) was significantly related to shorter survival (HR = 2.58, 95% CI 1.11-5.99, p = 0.028). In multivariate analysis, low TIL-Ts (HR = 6.48, 95% CI 2.16-19.46, p = 0.001) and high CD4:CD8 (> 1.2) (HR = 4.22, 95% CI 1.43-12.35, p = 0.009) were independent risk factors. For the risk stratification, three groups were defined based on TIL-Ts-related risk factors: low-risk group (high TIL-Ts and low CD4:CD8), intermediate risk group (low TIL-Ts, low CD4:CD8 or high TIL-Ts, high CD4:CD8) and high-risk group (low TIL-Ts and high CD4:CD8). The patients in high-risk group have significantly shorter survival than that in intermediate risk group (p = 0.025) and low-risk group (p = 0.002). This new risk stratification which is independent of performance status and age of the patients could hint the prognosis and may guide treatment of DLBCL.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Citometria de Fluxo , Linfoma Difuso de Grandes Células B , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Criança , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Taxa de Sobrevida
15.
Ann Hematol ; 98(2): 255-269, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30368587

RESUMO

Diffuse large B cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma (NHL), is a clinically and molecularly heterogeneous malignant lymphoproliferative disease. In the era of personalized medicine, genetic information is critical to early diagnosis, aiding risk stratification, directing therapeutic option, and monitoring disease relapse. However, lacking a circulating disease with most DLBCL cases hampers the acquisition of tumor genomic landscapes and disease dynamics. Circulating tumor DNA (ctDNA) is a novel noninvasive, real-time, and tumor-specific biomarker, reliably reflecting the comprehensive tumor genetic profiles, thus holds great promise in individualized medicine, including precise diagnosis and prognosis, response monitoring, and relapse detection of DLBCL. Here, we reviewed the recent advances of ctDNA in DLBCL and discussed its clinical values at different time points during the disease courses by comparing with the current routine methods in clinical practice. Collectively, we anticipated that ctDNA will ultimately be integrated into the management of DLBCL to facilitate precision medicine.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Linfoma Difuso de Grandes Células B/sangue , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia
16.
Platelets ; 30(5): 637-645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30047815

RESUMO

The international prognostic index (IPI) is a broadly utilized clinical tool to aid in predicting the prognosis of patients with aggressive non-Hodgkin's lymphomas (NHL). However, since this score was developed before the development of rituximab, and the introduction of combined rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) (R-CHOP) therapy for NHL has dramatically improved clinical outcomes, the IPI may be inadequate to assess prognosis in the R-CHOP era. In the present study, we assessed the utility of hemoglobin (Hb) level and platelet count to predict prognosis in diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), the largest category of aggressive NHL. A total of 89 patients newly diagnosed with nodal DLBCL, NOS and treated with R-CHOP therapy were included. The blood count results at diagnosis were statistically analyzed. Available biopsy specimens were immunostained for interleukin (IL)-6. Hb levels lower than 120 g/L (p = 0.0133) and platelet counts lower than 135 × 109/L (p = 0.0233) were associated with worse overall survival (OS). Based on those levels as cutoff values, a hemoglobin-platelet (HP) index was calculated by assigning 1 point for an Hb level or a platelet count lower than the cutoff. The patients were divided into three groups based on the HP index: high, with a score of 2 (n = 8); intermediate, with a score of 1 (n = 39); and low, with a score of 0 (n = 42). A higher HP index was associated with worse OS (p = 0.0055). Patients with IL-6-positive tumors had significantly lower Hb levels than those with IL-6-negative tumors (p = 0.0264), suggesting that abnormal production of IL-6 by lymphoma cells is associated with anemia. On the other hand, there was no association between the platelet counts and the IL-6 expression in the lymphoma cells. In a multivariate analysis, the HP index predicted OS rate independently of the IPI. Since the HP index is based on inexpensive and broadly available laboratory values, we believe that this index will have great utility in clinical practice, and the addition of this index to IPI could more precisely predict prognosis.


Assuntos
Hemoglobinas , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Contagem de Plaquetas , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/etiologia , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Citocinas/sangue , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Rituximab , Trombocitopenia/sangue , Trombocitopenia/etiologia , Vincristina/efeitos adversos , Vincristina/uso terapêutico
17.
Hematology ; 24(1): 103-107, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30198830

RESUMO

OBJECTIVES: Although many studies have assessed numerous molecular and immunohistochemical prognostic markers for diffuse large Bcell lymphoma (DLBCL), there is always a need for simple widely available markers. This study was planned to illustrate the clinical significance of baseline plasma fibrinogen levels in DLBCL patients. METHODS: We prospectively investigated 76 DLBCL patients treated with rituximab plus cyclophosphamide, vincristine, doxorubicin and hostacortine between August 2015 and February 2018. Baseline plasma fibrinogen level was measured and correlated with patients' clinical features, laboratory parameters, response to therapy, progression-free survival and overall survival. RESULTS: Significant association between fibrinogen level and clinical features such as the presence of B symptoms (P < .001) and clinical stage (P < .001) was observed while no association with age, gender, number of involved extranodal sites, performance status and international prognostic index (IPI) was found. Baseline fibrinogen level was significantly related to laboratory parameters including red cell distribution width (RDW) (P < .001), platelet count (P = .02), serum lactate dehydrogenase (LDH) (P = .009) and B2-microglobulin (P = .008). No statistically significant correlations were detected between baseline fibrinogen levels; and response to therapy, progression-free survival and overall survival. CONCLUSION: Baseline plasma fibrinogen level did not show prognostic significance for DLBCL patients, although it was associated with patients' clinical features and laboratory parameters. Being simple, cheap and widely available laboratory test, its use should be encouraged routinely in clinical practice to precisely clarify its predictive merit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/sangue , Fibrinogênio/metabolismo , Linfoma Difuso de Grandes Células B , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagem
18.
Hematology ; 24(1): 52-59, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30101679

RESUMO

OBJECTIVES: Chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with rituximab (R-CHOP) is currently the first-line therapy for diffuse large B-cell lymphoma (DLBCL). However, management of elderly patients is challenging and often requires dose reductions or prolonged treatment intervals. We investigated the proper dose of R-CHOP for them. METHODS: At our institute, for DLBCL patients aged 65-79 and ≥80 years, we had reduced CHOP dose to 5/6 and 7/12, respectively, and retrospectively evaluated the reduced-dose R-CHOP. RESULTS: Although the median age in the standard, 5/6, and 7/12-dose groups was 57, 73, and 84 years, respectively (p < 0.001), the 3-year event-free survival (EFS) rate did not differ between the standard and 5/6-dose groups (60.2 and 56.7%); however, 7/12-dose group had significantly inferior survival (25.9%). When patients aged 60-80 were evaluated, no difference in EFS was observed between the standard and 5/6-dose groups using the same international prognostic index. The neutrophil nadir and the frequency of infection were comparable among the three dose groups. DISCUSSION AND CONCLUSIONS: Reduced-dose R-CHOP chemotherapy is a promising treatment for elderly patients with DLBCL in terms of efficacy and toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Retrospectivos , Rituximab/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos
19.
BMC Cancer ; 18(1): 997, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340560

RESUMO

BACKGROUND: Systemic inflammation has been implicated in cancer development and progression. This study examined the best cutoff value of erythrocyte sedimentation rate (ESR) in diffuse large B-cell lymphoma (DLBCL) patients. METHODS: The relationship between ESR and clinical characteristics was analyzed in 182 DLBCL patients from 2006 to 2017. The log-rank test, univariate analysis, and Cox regression analysis were applied to evaluate the relationship between ESR and survival. An ESR of more than 37.5 mm/hour was found to be the optimal threshold value for predicting prognosis. RESULTS: ESR was associated with more frequent advanced Ann Arbor stage, poorer performance status, elevated lactate dehydrogenase level, the presence of B symptoms, high-risk International Prognostic Index (IPI 3-5), more extranodal involvement (ENI ≥2), non-germinal-center B-cell (non-GCB) subtypes, and more frequent Myc protein positivity. Shorter overall survival (OS) and progression-free survival (PFS) were found for patients with higher ESRs. Multivariate analysis demonstrated that ESR level is an independent prognostic factor of both OS and PFS. In addition, dynamic changes in ESR are valuable in assessing curative effect and predicting disease recurrence. CONCLUSION: High ESR in DLBCL patients indicated unfavorable prognosis that may require alternative treatment regimens.


Assuntos
Biomarcadores Tumorais/sangue , Mediadores da Inflamação/sangue , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Sedimentação Sanguínea , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto Jovem
20.
Best Pract Res Clin Haematol ; 31(3): 285-292, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30213398

RESUMO

Recent guidelines have de-emphasized the role of routine surveillance computed tomography (CT) scans for diffuse large B-cell lymphoma (DLBCL) patients who achieve a complete response to front-line therapy. This shift in practice recommendations was prompted by retrospective studies that failed to demonstrate clear clinical utility for surveillance CT in unselected DLBCL patients. Controversy remains, however, over the role of routine surveillance CT in the highest risk patients for treatment failure who would remain candidates for aggressive salvage therapies. Novel high-throughput sequencing methods can non-invasively monitor tumor-specific DNA in the blood and offers clear advantages designed to overcome fundamental limitations of CT scans. This review will discuss the current controversies surrounding monitoring clinical outcomes in aggressive B-cell lymphomas, with a specific emphasis on DLBCL. Fundamental limitations of imaging scans will be addressed and the potential of monitoring circulating tumor DNA as an adjunct or replacement for CT scans will be discussed.


Assuntos
DNA Tumoral Circulante/sangue , Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/terapia
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