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2.
Leukemia ; 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953029

RESUMO

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(3): 253-256, 2019 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-30835358

RESUMO

OBJECTIVE: To delineate laboratory and clinical characteristics of a case with chronic myelogenous leukemia (CML) and co-occurrence of t(9;22)(q34;q11) and t(8;21)(q22;q22). METHODS: The patient was subjected to cytogenetic, molecular, morphological and immunophenotypic analyses. RESULTS: Cytogenetic analysis revealed presence of t(8;21)(q22;q22) in addition to t(9;22)(q34;q11) in the patient. Chimeric BCR/ABL and AML1/ETO genes were detected by fluorescence in situ hybridization (FISH). Transcripts of BCR/ABL210 and AML1/ETO fusion genes were detected by relative quantity PCR. Morphological study suggested that the patient was at the chronic phase of CML. No significant immunophenotypic abnormality was detected by flow cytometry. CONCLUSION: Co-occurrence of t(8;21)(q22;q22) and t(9;22)(q34;q11) is rare in CML. Only 5 similar cases have been described previously. This case suggested that chromosomal alterations may precede morphological, flow cytometric and clinical changes and accelerate progression of the disease.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Translocação Genética , Aberrações Cromossômicas , Cromossomos Humanos , Proteínas de Fusão bcr-abl , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
4.
Int J Lab Hematol ; 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30264491

RESUMO

INTRODUCTION: The translocation t(8;21) is one of the most frequent chromosome translocations in AML. Molecular (cyto)genetics is regarded as the gold standard for diagnosis. However, due to the complicated variety of AML-related genetic abnormalities, comprehensive screening for all of these abnormalities may not be cost-effective. Therefore, a flow cytometric (FC) scoring system was generated in this study for rapid screening and diagnosis of t(8;21)AML. METHODS: The immunophenotypic characteristics of leukemic cells and neutrophils in cases with t(8;21) AML or other subtypes of AML were analyzed to find a method for the flow diagnosis of t(8;21) AML. RESULTS: In this study, we picked six FC features pointing to the diagnosis of t(8;21) AML: The blasts show high-intensity expression of CD34; aberrant expression of CD19, cCD79a, and CD56 in myeloblasts; co-expression of CD56 in neutrophils, especially in immature neutrophils; and a maturity disturbance in granulocytes. A six-point score was devised using these features. By ROC analysis, the AUC was 0.952, and the sensitivity, specificity, PPV, and NPV were 0.86, 0.90. 0.91, and 0.84 when the score was ≥3 points. The score was then prospectively validated on an independent cohort, and the AUC of the ROC curve for the validation cohort was 0.975. When the cutoff value was set at 3, the obtained sensitivity and specificity values were 0.91 and 0.94, respectively. CONCLUSIONS: The FC score described can be used for the identification and rapid screening of t(8;21) AML.

5.
HLA ; 92(5): 312-313, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30079569

RESUMO

HLA-C*06:02:47 differs from HLA-C*06:02:01:01 (444C → T, exon 3, I124I), resulting in a synonymous change.

6.
Exp Hematol Oncol ; 7: 19, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30155344

RESUMO

Background: The positive association of multiple myeloma (MM) risk with HLA-C loci C*07:02 g and C*02:02 g, and the negative association of that with C*05:01 g were statistically significant in Whites have recently been reported. However, no association between HLA-C alleles and MM risk was found in Asians/Pacific Islanders. Here we identified 316 Chinese patients with MM, and reported the results of our investigation of HLA-C in MM in Chinese population. Methods: We identified 316 Chinese patients with MM diagnosed in our hospital, and typed for HLA-C by using Sanger sequence-based typing. The control was from laboratories of China Marrow Donor Program (CMDP), where HLA high resolution was provided in 564,856 volunteer adult donors. Results: In contrast to the association of MM risk in Whites, we did not find the similar association in Chinese population. Nevertheless, four new associations between the MM risk were identified in Chinese patients. Our data demonstrated that Chinese patients with MM carry significantly increased frequencies of HLA-C*03:03 (FDR = 0.0269), HLA-C*07:63 (FDR = 0.0278) and HLA-C*08:22 (FDR = 0.0442) comparing with controls, while significantly decreased frequency of HLA-C*01:02 (FDR = 0.0414) comparing with controls. Conclusion: Therefore, HLA-C region is a key risk locus for MM in Chinese population.

7.
Oncol Lett ; 15(4): 5359-5367, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29552179

RESUMO

The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), ETS variant 6 (ETV6), RB transcriptional corepressor 1 (RB1), BTG anti-proliferation factor 1 (BTG1), early B-cell factor 1 (EBF1), cyclin dependent kinase inhibitor 2A/2B (CDKN2A/2B) and cytokine receptor like factor 2 (CRLF2) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China. The effects of CNAs on prognosis were analyzed. Gene deletions were detected in 58/87 (66.7%) ALL patients. The most common deletions were observed in the following genes: IKZF1 (40.6%), CDKN2A (31.9%), CDKN2B (29%), PAX5 (21.7%), RB1 (14.5%) and BTG1 (10.1%). B cell-ALL (B-ALL) patients with CDKN2A/2B deletions exhibited poor 2-year overall survival (OS; P=0.055) and relapse-free survival (RFS; P=0.054) rates. CDKN2A/2B deletions were associated with poor 2-year OS (P=0.045) and RFS (P=0.071) rates in Philadelphia chromosome positive (Ph+) B-ALL patients, as well as in the high risk (HR) B-ALL group (P=0.037 and P=0.047, respectively). Patients with PAX5 deletions displayed poor 2-year OS (P=0.004) and RFS (P=0.016) rates in Philadelphia chromosome negative (Ph-) B-ALL patients. Patients with ≥3 gene deletions exhibited a poorer prognosis than other patients (OS, P=0.001; RFS, 0.002).

8.
Lancet ; 391(10133): 1927-1938, 2018 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-29550029

RESUMO

As global efforts accelerate to implement the Sustainable Development Goals and, in particular, universal health coverage, access to high-quality and timely pathology and laboratory medicine (PALM) services will be needed to support health-care systems that are tasked with achieving these goals. This access will be most challenging to achieve in low-income and middle-income countries (LMICs), which have a disproportionately large share of the global burden of disease but a disproportionately low share of global health-care resources, particularly PALM services. In this first in a Series of three papers on PALM in LMICs, we describe the crucial and central roles of PALM services in the accurate diagnosis and detection of disease, informing prognosis and guiding treatment, contributing to disease screening, public health surveillance and disease registries, and supporting medical-legal systems. We also describe how, even though data are sparse, these services are of both insufficient scope and inadequate quality to play their key role in health-care systems in LMICs. Lastly, we identify four key barriers to the provision of optimal PALM services in resource-limited settings: insufficient human resources or workforce capacity, inadequate education and training, inadequate infrastructure, and insufficient quality, standards, and accreditation.


Assuntos
Serviços de Laboratório Clínico , Necessidades e Demandas de Serviços de Saúde , Qualidade da Assistência à Saúde , Países em Desenvolvimento , Educação em Saúde , Humanos , Vigilância da População , Saúde Pública , Qualidade da Assistência à Saúde/normas , Cobertura Universal do Seguro de Saúde , Recursos Humanos
9.
Oncotarget ; 9(3): 3353-3364, 2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29423051

RESUMO

B-cell chronic lymphoproliferative disorders (B-CLPD) comprise several entities with indolent clinical manifestations but heterogeneous survival. Cytogenetic aberrations are now the standard prognostic predictors in chronic lymphocytic leukemia (CLL) but have been less investigated in other subtypes of B-CLPD. In this study, we detected cytogenetic aberrations by fluorescence in situ hybridization (FISH) in 875 B-CLPD patients, based on a panel probes locating at 13q14, 11q22, 17p13 and CEP12. We identified del17p acted as the independent adverse cytogenetic predictor for overall survival (OS) in CLL. Del13q, del11q and del17p were adverse factors for OS in Waldenström's macroglobulinemia in the univariate analysis but lost their role in the multivariate analysis. Trisomy 12 acted as an independent poor factor for both marginal zone lymphoma (MZL) and unclassified B-CLPD (BCLPD-U) subtype. Del17p did not impact survival in MZL and BCLPD-U patients. These contrasting results indicate different roles of the same cytogenetic aberrations in the pathogenesis of each B-CLPD subtype. As del17p contributed to the poorest survival in CLL and desired extraordinary treatment strategy, the imitation of CLL strategy to other B-CLPD with del17p should be carefully advocated based on this study.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 58-64, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397819

RESUMO

OBJECTIVE: To investigate the effect of loss of heterozygosity(LOH) in HLA region at initial diagnosis and remission of leukemia patient before transplantation on HLA typing. METHODS: The HLA typing was performed in DNA extracted from peripheral blood obtained at diagnosis (Sample 1 and Sample 2) and remission (Sample 3) in one pretransplant male patient with mixedphenotype acute leukemia (MPAL). HLA typing for HLA-A, B, C, DQB1, DRB1 was performed by Sequence-based typing (SBT), Sequence-specific oligonucleotide probe hybridization (SSO) and Sequence-specific primers (SSP). To define more precisely a cutoff limit for the detection of a heterozygous DNA present in a fraction of the cells by the SBT technology, DNA mixing experiments were performed. RESULTS: SBT results showed that Sample 1 and Sample 2 were both homozygous HLA results at five loci (lost one haplotype) although the sequencing background of Sample 1 was a little high. Except HLA-C locus was homozygous, Sample 3 was heterozygous HLA results at four loci. Based on DNA mixing experiments, a cutoff limit for the detection of heterozygous DNA was 20% by SBT technology, and a detection threshold for HLA-A, B, C, DQB1, DRB1 heterozygosity in blood samples was <75% blasts. CONCLUSION: Because LOH may be partial, any homozygous HLA result obtained during a blast crisis, especially ≥75% blasts, would have to be confirmed by a second typing on a buccal swab or on peripheral blood from the patient in complete remission.


Assuntos
Perda de Heterozigosidade , Alelos , Primers do DNA , Genótipo , Teste de Histocompatibilidade , Humanos , Masculino
11.
Genes Chromosomes Cancer ; 57(2): 80-88, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29057546

RESUMO

U2AF1 mutations (U2AF1MT) occur commonly in myelodysplastic syndromes (MDS) without ring sideroblasts. The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS. We performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty-six patients (17%) were found to have U2AF1MT, which occurred more common in younger patients (P = .001) and represented ancestral lesions in a substantial proportion (71%) of cases. ASXL1MT and isolated +8 were significantly enriched in U2AF1MT-positive cases, whereas TP53MT, SF3B1MT, and complex karyotypes were inversely associated with U2AF1MT. U2AFS34 subjects were enriched for isolated +8 and were inversely associated with complex karyotypes. U2AF1MT was significantly associated with anemia, thrombocytopenia, and poor survival in both lower-risk and higher-risk MDS. U2AF1S34 subjects had more frequently platelet levels of <50 × 109 /L (P = .043) and U2AF1Q157 /U2AF1R156 subjects had more frequently hemoglobin concentrations at <80 g/L (P = .008) and more often overt fibrosis (P = .049). In conclusion, our study indicates that U2AF1MT is one of the earliest genetic events in MDS patients and that different types of U2AF1MT have distinct clinical and biological characteristics.


Assuntos
Síndromes Mielodisplásicas/genética , Fator de Processamento U2AF/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Análise Mutacional de DNA/métodos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Síndromes Mielodisplásicas/metabolismo , Prognóstico , Análise de Sequência de DNA/métodos , Fator de Processamento U2AF/metabolismo
12.
Oncotarget ; 8(58): 98757-98770, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29228725

RESUMO

Splenic marginal zone lymphoma (SMZL) is a rare indolent B-cell neoplasm with hepatitis virus supposed to involve in the pathogenesis. The characteristics of SMZL derived from Caucasia population and high hepatitis C virus (HCV) infection region have been widely investigated, but few was reported in the Eastern population with HBV prevalent region. We analyzed the clinical characteristics, cytogenetic aberrations and prognostic factors in 160 SMZL patients from China. 25 patients (16%) were HBsAg-positive and 54 (34%) patients with resolved HBV infection. IGH gene usage was analyzed in 39 patients. The preferential usages of IGHV genes were IGHV1-2 (26%), followed by IGHV4-34 (18%) and IGHV2-70 (10%). The patients with HBV infection presented biased IGHV-D-J rearrangements and mutational status. Using three independent factors hemoglobin level, HBsAg positivity and complex karyotype, we developed a new hierarchical prognostic model, which showed a better c-index than the previously reported IIL and HPLL scoring systems in SMZL. In conclusion, SMZL in HBV prevalent region have unique clinical and biological characteristics and new prognostic scoring model should be adopted in this population.

13.
Chin Med J (Engl) ; 130(22): 2686-2690, 2017 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-29133756

RESUMO

BACKGROUND: Overexpression and constitutive activation of signal transducer and activator of transcription (STAT) 3 have been suggested in the tumorigenesis of many human cancers, including multiple carcinomas, melanoma, and lymphoma. The diagnosis of hepatocellular carcinoma (HCC) in lobectomy specimens is usually straightforward, but distinguishing cirrhosis from well-differentiated HCC can be challenging in core biopsies. Our aims were to investigate the expression level of STAT3 and phosphorylated STAT3 (pSTAT3) in HCC and cirrhosis, and the application of STAT3 in the differential diagnosis of HCC and cirrhosis. METHODS: Sixty cases were divided into three groups: patients with HCC only (Group 1), HCC and cirrhosis (Group 2), and cirrhosis only (Group 3). Formalin-fixed and paraffin-embedded tissue sections were stained immunohistochemically for STAT3, pSTAT3, and CD163. The values obtained from the tissue sections of each group were compared in statistical analysis. RESULTS: STAT3 showed a high level in HCC and was a significant marker for differentiating HCC from cirrhosis (P < 0.0001). The odds ratio between HCC and cirrhosis increased 34.4 times when the intensity of STAT3 increased by 1 level. Spearman's correlation and Chi-square tests also demonstrated that expression level of STAT3 did not correlate with age, gender, or the presence of a cirrhotic background. CONCLUSIONS: STAT3 staining differs significantly in HCC and cirrhosis. The findings reinforce the role of STAT3 in the tumorigenesis of HCC and provide a useful marker to differentiate HCC from cirrhosis in challenging liver biopsies.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fator de Transcrição STAT3/metabolismo , Adulto , Carcinoma Hepatocelular/patologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Feminino , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fosforilação , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(3): 683-687, 2017 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28641618

RESUMO

OBJECTIVE: To investigate the clinical and cytogenetic characteristics of high-level mixed-lineage leukaemia (MLL) gene amplification in patients with acute myeloid leukemia (AML). METHODS: The clinical and cytogenetic data of 2 AML patients with high-level MLL amplification from January 2010 to August 2016 were analyzed retrospectively. RESULTS: The two AML cases were in middle-aged population. They were diagnosed as FAB subtype M5b and M2a respectively. Both of them had complex karyotypes with the aberrations of chromosome 11. One case was confirmed as MLL-PTD involving exons 2-9 by RT-PCR and sequencing. The other case without MLL-PTD was further analyzed by CytoScan HD analysis. The CMA results showed partial gain of 11q accompanied with partial loss in 11q, deletion of regions in 3p, 3q, 4q, 5q, 7q, 8q, 10p, 10q, 12p and 18q, as well as gain of 4p. CONCLUSION: The co-existence of -5/5q-, -7/7q- and highly complex karyotype may accelerate the poor prognosis. Thus how those cytogenetic abnormalities influencing the disease prognosis need to be further explored.


Assuntos
Aberrações Cromossômicas , Histona-Lisina N-Metiltransferase/genética , Cariotipagem , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Transtornos Cromossômicos , Cromossomos Humanos Par 11 , Citogenética , Humanos
15.
J Hematol Oncol ; 10(1): 61, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28245838

RESUMO

Target-specific next-generation sequencing technology was used to analyze 112 genes in adult patients with acute lymphoblastic leukemia (ALL). This sequencing mainly focused on the specific mutational hotspots. Among the 121 patients, 93 patients were B-ALL (76.9%), and 28 patients (23.1%) were T-ALL. Of the 121 patients, 110 (90.9%) harbored at least one mutation. The five most frequently mutated genes in T-ALL are NOTCH1, JAK3, FBXW7, FAT1, and NRAS. In B-ALL, FAT1, SF1, CRLF2, TET2, and PTPN1 have higher incidence of mutations. Gene mutations are different between Ph+ALL and Ph-ALL patients. B-ALL patients with PTPN11 mutation and T-ALL patients with NOTCH1 and/or FBXW7 mutations showed better survival. But B-ALL with JAK1/JAK2 mutations showed worse survival. The results suggest that gene mutations exist in adult ALL patients universally, they are related with prognosis.


Assuntos
Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Prognóstico , Adulto Jovem
16.
BMC Med Genet ; 18(1): 16, 2017 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-28209136

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) of leukemic phase is a rare clinical manifestation, but is highly prevalent with central nervous system involvement (CNSI). Little is known about this rare clinical observation. METHODS: We reviewed the clinical characteristics of 40 DLBCL patients with leukemic phase identified by flow cytometry and analyzed BCL2 and MYC aberrations by fluorescence in situ hybridization. RESULTS: The median age of these 40 patients was 46 years (range, 15-75) with 19 men patients. All patients had bone marrow involvement, and fourteen (35.0%) had CNSI. There were respectively 14 patients (35.0%) had the BCL2 or MYC gain/amplification and nine of them (22.5%) simultaneously had both aberrations. Compared to those without CNSI, CNSI was found more commonly in male patients (71.4 vs. 34.6%, p = 0.046), in those with IPI scores of 4-5 (57.1% vs. 11.5%, p = 0.001), and in those with elevated serum LDH (100 vs. 61.5%, p = 0.007) and both MYC and BCL2 rearrangement (88.9 vs. 19.4%; p = 0.000). BCL2 and MYC rearrangements were the sole independent factor correlated with CNSI. CONCLUSION: It is possible that both BCL2 and MYC gene aberrations may contribute to the high incidence of CNSI observed in leukemic phase of patients with DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/metabolismo , Medula Óssea/patologia , Sistema Nervoso Central/metabolismo , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , L-Lactato Desidrogenase/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Transplante de Células-Tronco , Taxa de Sobrevida , Transplante Autólogo , Adulto Jovem
17.
Am J Clin Pathol ; 147(1): 15-32, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28158414

RESUMO

Objectives: We review the current status of pathology services in low- and middle-income countries and propose an "essential pathology package" along with estimated costs. The purpose is to provide guidance to policy makers as countries move toward universal health care systems. Methods: Five key themes were reviewed using existing literature (role of leadership; education, training, and continuing professional development; technology; accreditation, management, and quality standards; and reimbursement systems). A tiered system is described, building on existing proposals. The economic analysis draws on the very limited published studies, combined with expert opinion. Results: Countries have underinvested in pathology services, with detrimental effects on health care. The equipment needs for a tier 1 laboratory in a primary health facility are modest ($2-$5,000), compared with $150,000 to $200,000 in a district hospital, and higher in a referral hospital (depending on tests undertaken). Access to a national (or regional) specialized laboratory undertaking disease surveillance and registry is important. Recurrent costs of appropriate laboratories in district and referral hospitals are around 6% of the hospital budget in midsized hospitals and likely decline in the largest hospitals. Primary health facilities rely largely on single-use tests. Conclusions: Pathology is an essential component of good universal health care.


Assuntos
Laboratórios Hospitalares/economia , Patologia/economia , Países em Desenvolvimento , Humanos , Patologia/educação
18.
Genet Med ; 19(2): 182-191, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27467457

RESUMO

PURPOSE: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with cytogenetic aberrations that are still considered the gold standard of prognostic factors. However, heterogeneity remains within each cytogenetic group, especially in patients with concomitant cytogenetic aberrations. METHODS: A panel of DNA probes was used to detect cytogenetic aberrations, including RB1/D13S25 at 13q14, ATM at 11q22, TP53 at 17p13, CEP12 and IGH translocation at 14q32, by fluorescence in situ hybridization. A comprehensive method integrating the number of cytogenetic aberrations and intratumoral genetic heterogeneity was used to analyze the prognosis for patients with concomitant aberrations. RESULTS: Within the conventional favorable or neutral prognostic groups (i.e., with del 13q, trisomy 12, and/or t(14q32)), the coincidence of these three aberrations worsened survival in terms of time to first therapy, progression-free survival, and overall survival. However, within the conventional unfavorable prognostic group (i.e., del 11q or del 17p), patients with a minor unfavorable clone had an unexpected survival advantage compared with patients with a major unfavorable clone. A new cytogenetic prognostic system that integrates the number of cytogenetic aberrations and intratumoral genetic subclones was more precise than the conventional system. CONCLUSION: The number of cytogenetic aberrations and the size of intratumoral genetic subclones should be comprehensively considered to determine the prognosis for CLL.Genet Med 19 2, 182-191.


Assuntos
Heterogeneidade Genética , Leucemia Linfocítica Crônica de Células B/genética , Prognóstico , Translocação Genética/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Deleção Cromossômica , Análise Citogenética/métodos , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/fisiopatologia , Masculino , Pessoa de Meia-Idade
19.
Asia Pac J Clin Oncol ; 13(2): e111-e116, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25869382

RESUMO

AIM: To evaluate the efficacy and safety of late-course hypofractionated radiation treatment of muscle-invasive bladder carcinoma after bladder-conserving surgery. METHODS: Seventy-six patients with transitional cell bladder carcinoma, stage II (T2-4N0M0), after transurethral resection, were enrolled. Pirarubicin was given at 30 mg/m2 and 100 mL physiological saline once weekly (QW) for 12 weeks through and after intravesical instillation postoperatively. Radiation schedule delivered 46 Gy in 20 fractions for planning target volume, with an additional 20 Gy in five fractions for gross tumor volume as late-course radiation. Chemotherapy was stopped if Radiation Therapy Oncology Group grade 3 or higher bladder or bowel toxicity occurred. The primary end points were acute toxicity, local control and patients' survival. RESULTS: One-, three- and five-year overall survival rates were 98, 78 and 69.5%, respectively. Mean survival time was 58.4 months (95% CI: 52.6, 64.2). In addition, 1-, 3- and 5-year local control rates were 100, 80.5 and 76.1%, respectively. Mean local control time was 60.7 months (95% CI: 55.1, 66.3). The cumulative incidence of local/regional failure and distant failure was 28.9%. The rate of single local/regional failure was 13.2%, but distant failure rate was 21.1%. CONCLUSIONS: Concurrent pirarubicin-based late-course hypofractionated radiation therapy showed desirable local control rate and acceptable toxicity. It could be used after bladder-conserving surgery to allow patients to preserve their bladder.


Assuntos
Carcinoma de Células de Transição/radioterapia , Fracionamento da Dose de Radiação , Neoplasias da Bexiga Urinária , Idoso , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipofracionamento da Dose de Radiação , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgia
20.
Oncotarget ; 8(12): 18792-18801, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27852046

RESUMO

Elevated inflammatory markers are associated with poor outcomes in various types of cancers; however, their clinical significance in multiple myeloma (MM) have seldom been explored. This study investigated the prognostic relevance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in MM. Totally 559 MM patients were included in this study. NLR, PLR and MLR were calculated from whole blood counts prior to therapy. Kaplan-Meier curves and multivariate Cox proportional models were used for the evaluation of the survival. It has shown that newly diagnosed MM patients were characterized by high NLR and MLR. Elevated NLR and MLR and decreased PLR were associated with unfavorable clinicobiological features. Applying cut-offs of 4 (NLR), 100 (PLR) and 0.3 (MLR), elevated NLR, MLR and decreased PLR showed a negative impact on outcome. Importantly, elevated NLR and decreased PLR were independent prognostic factors for progression-free survival. Thus, elevated NLR and MLR, and decreased PLR predict poor clinical outcome in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.


Assuntos
Biomarcadores Tumorais/imunologia , Contagem de Leucócitos , Mieloma Múltiplo/imunologia , Adulto , Idoso , Área Sob a Curva , Plaquetas , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Neutrófilos , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e Especificidade
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