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2.
Cancer Med ; 13(5): e7062, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38491815

RESUMO

BACKGROUND: Blinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes. METHODS: We conducted a retrospective real-world cohort analysis in 20 newly diagnosed B-ALL patients who received reduced-dose chemotherapy (idarubicin, vindesine, and dexamethasone) for 1-3 weeks, followed by blinatumomab for 1-4 weeks as an induction therapy. RESULTS: At the end of the induction therapy, a complete remission rate of 100% was achieved; 17 (85%) patients were minimal residual disease (MRD) negative (<1 × 10-4 ). Adverse events (AEs) were reported in 12 (60%) patients-43.8% were grade 1-2 and 56.2% were grade 3-4. No incidence of neurotoxicity or grade ≥3 cytokine release syndrome was reported. CONCLUSIONS: Blinatumomab demonstrated a significant improvement in clinical outcomes in patients with newly diagnosed B-ALL irrespective of their poor-risk factor status and the pretreatment blast burden.


Assuntos
Anticorpos Biespecíficos , Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Estudos Retrospectivos , Quimioterapia de Indução , Anticorpos Biespecíficos/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Linfoma de Burkitt/tratamento farmacológico
3.
Ann Hematol ; 103(4): 1181-1185, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294534

RESUMO

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia that is distinguished by the chromosomal translocation t(15;17)(q24;q21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA). Recently, we identified a novel fusion gene in APL, RARA::ankyrin repeat domain 34C (ANKRD34C), identified its functions by morphological, cytogenetic, molecular biological and multiplex fluorescence in situ hybridization analyses, and demonstrated the potential therapeutic effect clinically and experimentally of all-trans retinoic acid (ATRA); the findings have important implications for the diagnosis and treatment of atypical APL.


Assuntos
Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/tratamento farmacológico , Hibridização in Situ Fluorescente , Tretinoína/uso terapêutico , Receptor alfa de Ácido Retinoico/genética , Proteínas de Transporte/genética , Translocação Genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo
4.
Int J Antimicrob Agents ; 62(1): 106841, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37160241

RESUMO

In the current study, a population pharmacokinetic (PPK) model was developed for biapenem in patients with febrile neutropenia (FN) and haematological malignancies. Through Monte Carlo simulation, optimal administration regimens were suggested based on the developed PPK model. In a prospective, single-centre, open-label study, 174 plasma samples from 120 Chinese patients with FN and haematological malignancies were analysed by chromatography, and PK parameters were analysed by NONMEM. The drug clearance process was influenced by crucial covariates, namely creatinine clearance (CLCR) and concomitant posaconazole (POS). The ultimate PPK model was as follows: CL (L/h)=29.81 × (CLCR/121.38)0.806 × (1-POS × 0.297); volume of distribution (L)=114. For the target of ≥40% fT>minimum inhibitory concentration (MIC) (duration that the plasma level exceeds the MIC of the causative pathogen) and achieving the probability of target attainment ≥90%, the PK/pharmacodynamic breakpoint was 2 mg/L for the 2.4 g/day dosing regimen consisting of 600 mg q6h and 800 mg q8h. The breakpoint was 1 mg/L for the 1.2 g/day dosing regimen consisting of 300 mg q6h and 600 mg q12h. Empirical therapy would benefit from utilizing higher dosages and extended infusion durations. Therefore, it is suggested that patients with symptoms that are strongly suggestive of Pseudomonas aeruginosa or Acinetobacter baumannii infection may be suitable for combined treatment with other antibacterial drugs.


Assuntos
Infecções por Acinetobacter , Neutropenia Febril , Neoplasias Hematológicas , Humanos , Método de Monte Carlo , Estudos Prospectivos , Antibacterianos/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Neutropenia Febril/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Testes de Sensibilidade Microbiana
5.
BMC Cancer ; 20(1): 195, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143579

RESUMO

BACKGROUND: Donor acute lymphoblastic leukemia with recipient intact is a rare condition. We report a case of donor developing acute lymphoblastic leukemia 8 yrs after donating both bone marrow and peripheral blood hematopoietic stem cells. CASE PRESENTATION: This case report describes a 51-year old female diagnosed with acute lymphoblastic leukemia who donated both bone marrow and peripheral blood stem cells 8 yrs ago for her brother with severe aplastic anemia. Whole exome sequencing revealed leukemic genetic lesions (SF3B1 and BRAF mutation) only appeared in the donor sister, not the recipient, and an unusual type of hematopoietic stem cell transplantation with the recipient's peripheral blood stem cells was done. The patient remained in remission for 3 months before disease relapsed. CD19 CAR-T therapy followed by HLA-identical unrelated hematopoietic stem cell transplantation was applied and the patient remains in remission for 7 months till now. CONCLUSIONS: This donor leukemia report supports the hypothesis that genetic lesions happen randomly in leukemogenesis. SF3B1 combined with BRAF mutation might contribute to the development of acute lymphoblastic leukemia.


Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Doadores de Tecidos , Anemia Aplástica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fosfoproteínas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Fatores de Processamento de RNA/genética , Transplante Homólogo , Sequenciamento do Exoma
6.
Oncol Lett ; 18(6): 6196-6206, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788095

RESUMO

Hepatitis B virus (HBV) is a hepatotropic and a lymphotropic virus. An association between HBV and hematologic malignancies has been determined previously; however, the association between HBV infection and multiple myeloma (MM) remains controversial. The present study aimed to assess the prevalence of HBV infection in patients with MM, and investigate their characteristics and prognostic significance. The clinical data of 165 patients with MM who had received at least four cycles of chemotherapy between April 2008 and February 2017 at Nanjing Drum Tower Hospital (Nanjing, China) were collected. HBV markers were determined using ELISA. The rates of acute or chronic HBV infection and resolved HBV infection in patients with MM were 12.12 and 26.06%, respectively. The gain of 1q21 was significantly more prevalent in the patients who were classified as HBV-positive compared with the patients who were classified as HBV-negative (54 vs. 38.2%; P=0.048), and the level of alanine transaminase in patients who were classified as HBV-positive was significantly increased compared with the non-infected group (63.29 vs. 24.66 U/l; P=0.043). Lactate dehydrogenase, serum creatinine and serum calcium levels were additionally determined to be significant risk factors of overall survival. The progression-free survival (PFS) of patients who were classified as HBV-positive was decreased compared with patients who were classified as HBV-negative (18.97 vs. 29.67 months; P=0.006), and being HBV-positive was determined to be an independent prognostic factor of PFS. HBV infection may contribute to MM progression through 1q21 amplification, and improved monitoring of HBV markers in patients with MM may be required.

7.
Oncotarget ; 8(39): 65609-65619, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29029457

RESUMO

Primary bone lymphomas (PBLs) are composed of malignant lymphoid cells presenting in osseous sites, without supra-regional lymph node or extranodal involvement. We systematically characterized the immunophenotype and the myeloid differentiation factor 88 (MYD88)-L265P gene mutation status in PBL. Clinical data from 19 patients with PBL treated at Nanjing Drum Tower Hospital between 2009 and 2015 were analyzed retrospectively. Protein expression patterns were identified immunohistochemically, and MYD88 mutation was assessed using polymerase chain reaction and direct DNA sequencing. Fifteen patients presented with diffuse large B-cell lymphoma. Clinical factors favoring a good prognosis were an age < 60 years and rituximab treatment. B-cell lymphoma 2 expression was detected in 5/15 diffuse large B-cell lymphoma patients, and was associated with a poor prognosis in a univariate model. Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling factors were upregulated in PBLs. All eighteen evaluable PBL samples harbored wild-type MYD88. These data thus suggest that age and rituximab treatment are independent prognostic factors determining overall survival, and that activation of JAK/STAT3 signaling may promote the pathogenesis of PBL. Moreover, the absence of MYD88-L265P mutation in PBL indicate there are distinct pathogenetic backgrounds among extranodal lymphomas.

8.
Oncotarget ; 8(6): 9708-9716, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28039454

RESUMO

PURPOSE: We estimated the expression of nuclear factor kappa B/p65 in non-germinal center B-cell-like subtype diffuse large B-cell lymphoma, to investigate its relationship to clinicopathological features, and to further evaluate its prognostic value and clarify its impact on survival. RESULTS: Among the 49 patients enrolled in this study, 14 (28.6%) had positive p65 expression. The negative p65 group had significantly better survival compared to the positive p65 group in terms of both the 3-year estimated OS (91.2% vs. 39.3%, p = 0.003) and PFS (75.6% vs. 26.5%, p = 0.002). In patients with 4 or more risk factors, p65 was an independent prognostic factor of OS (HR 5.99, 95%CI=1.39-25.75, p=0.016) and PFS (HR 4.01, 95%CI=1.15-14.00, p=0.029). MATERIALS AND METHODS: The expression of the NF-κB/p65 protein was deteremined by immunohistochemistry in 49 non-GCB DLBCL. Survival was assessed by the Kaplan-Meier method and Cox multivariate analysis. The median patient follow-up period was 24 months. CONCLUSIONS: The expression of NF-κB/p65 has prognostic value in high risk non-GCB DLBCL, and it is a suitable target for the development of new therapies.


Assuntos
Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/química , Fator de Transcrição RelA/análise , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
9.
Hematology ; 22(3): 145-148, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27875935

RESUMO

BACKGROUND: Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. METHODS: Assessing the prevalence of molecular mutations in Chinese Han patients with essential thrombocythemia (ET), and correlating their mutational profile with disease characteristics/phenotype. RESULTS: Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2, CALR, and MPL (so-called triple-negative ET). Mutations in JAK2 exon 12 were not detected in any patient. Two ET patients had both CALR and JAK2 V617F mutations. Comparing the hematological parameters of the patients with JAK2 mutations with those of the patients with CALR mutations showed that the ET patients with CALR mutations were younger (p = 0.045) and had higher platelet counts (p = 0.043). CONCLUSION: Genotyping for CALR could be a useful diagnostic tool for JAK2/MPL-negative ET, since the data suggest that CALR is much more prevalent than MPL, therefore testing for CALR should be considered in patients who are JAK2 negative as its frequency is almost 20 times that of MPL mutation.


Assuntos
Povo Asiático/genética , Calreticulina/genética , Janus Quinase 2/genética , Mutação , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , China , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/tratamento farmacológico , Adulto Jovem
10.
Medicine (Baltimore) ; 95(38): e4893, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27661033

RESUMO

This study aims to investigate whether neutrophil to lymphocyte ratio (NLR) is an independent predictor in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. Data from newly diagnosed DLBCL patients at Nanjing Drum Tower Hospital from 2006 to 2015 were retrospectively reviewed. We used the receiver operating characteristic (ROC) curve analysis to generate the optimal cutoff value for NLR. Among those 156 patients enrolled, the NLR was < 3.0 in 46.8% (73/156) of the patients, and the remaining 53.2% (83/156) had an NLR ≥ 3.0. Patients with higher pretreatment NLR were found to correlate with poorer OS and PFS than these with lower NLR (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.43-4.97, P = 0.002 and HR = 1.79, 95% CI = 1.05-3.07, P = 0.034, respectively). The multivariate Cox proportional hazard model analysis further showed that high NLR was found independently predictive of poor OS (HR = 0.40; CI = 0.19-0.84, P = 0.015) and PFS (HR = 0.57; CI = 0.33-0.98, P = 0.042). Consequently, pretreatment NLR was an independent prognostic predictor in patients with DLBCL in the rituximab era.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neutrófilos/patologia , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Contagem de Linfócitos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Rituximab/administração & dosagem , Análise de Sobrevida , Vincristina/uso terapêutico
11.
Histol Histopathol ; 31(3): 285-92, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26424560

RESUMO

The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with diffuse large B-cell lymphoma (DLBCL) for the past 20 years. The utility of the IPI must be reassessed in the era of immunochemotherapy. Seven risk factors at diagnosis were identified, and a maximum of 7 points were assigned to each patient. Four risk groups were created: low (0-1), low-intermediate (2-3), high-intermediate (4), and high (5-7). Using MYC and BCL-2 clinical data from the Drum Tower Hospital collected during the rituximab era, we performed a retrospective analysis of patients with DLBCL treated with R-CHOP and built an biological markers adjusted IPI with the goal of improving risk stratification.Clinical features from 60 adults with de novo DLBCL diagnosed from 2008-2013 were assessed for their prognostic significance. The IPI remains predictive, but it cannot identify the high-risk subgroup. Compared with the IPI, the MYC and BCL-2 adjusted-IPI (A-IPI) better discriminated patients in the high-risk subgroup (4-year overall survival [OS]: 33.3%) than did the IPI (4 year OS: 48.0%). In the era of R-CHOP treatment, MYC and BCL-2 adjusted-IPI is more powerful than the IPI for helping guide treatment planning and interpretation of clinical trials.


Assuntos
Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-myc/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Intervalo Livre de Doença , Doxorrubicina , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-myc/análise , Estudos Retrospectivos , Fatores de Risco , Rituximab , Vincristina , Adulto Jovem
12.
Tumour Biol ; 35(7): 6757-62, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24719189

RESUMO

This study aims to investigate the prognostic significance of the MYC protein expression in diffuse large B cell lymphoma (DLBCL) patients treated with RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). A total of 60 patients with DLBCL from 2008 to 2013 were included. Formalin-fixed, paraffin-embedded DLBCL samples were analyzed for MYC protein expression and divided into high or low MYC group. The MYC protein expression and the international prognostic variables were evaluated. The high MYC protein expression predicted a shorter 3-year estimated overall survival (OS) and progression-free survival (PFS) versus the low MYC protein expression (57 % vs. 96 %, P < 0.001 and 50 % vs. 96 %, P = 0.001, respectively). Multivariate analysis confirmed the prognostic significance of the MYC protein expression for both OS (HR, 11.862; 95 % CI, 1.462-96.218; P = 0.021) and PFS (HR, 6.073; 95 % CI, 1.082-34.085; P = 0.040). MYC protein expression with International Prognostic Index (IPI) score distinguished patients into three risk groups with different 3-year OS rates (χ (2) 23.079; P < 0.001) and distinct 3-year PFS rates (χ (2) 15.862; P < 0.001). This study suggests that the MYC protein expression is an important inferior prognostic factor for survival in patients with DLBCL treated with RCHOP. The combinative model with IPI score and MYC protein expression could stratify DLBCL patients into prognostically relevant subgroups more effectively than either the IPI or the MYC alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Proteínas Proto-Oncogênicas c-myc/biossíntese , Rituximab , Vincristina/administração & dosagem
13.
PLoS One ; 8(4): e60699, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23593285

RESUMO

BACKGROUND: To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia. METHODS: A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission. RESULTS: Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07-1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45-0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81-0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80-1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits. CONCLUSION: Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Humanos , Idarubicina/administração & dosagem , Quimioterapia de Indução , Pessoa de Meia-Idade , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Neurol Sci ; 33(4): 881-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22160751

RESUMO

Autologous haematopoietic stem cell transplantation (AHSCT) is a promising treatment for multiple sclerosis (MS) patients who have not adequately responded to conventional therapies. We retrospectively evaluated the safety and long-term clinical outcome of AHSCT in MS patients in China. Twenty-five patients with various types of MS were treated with AHSCT. Peripheral blood stem cells were derived by leukapheresis after mobilized with granulocyte colony-stimulating factor. Then CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion, with the conditioning regimen BEAM adopted and early and late toxicities recorded. Long-term responses were evaluated by the expanded disability status scale (EDSS), progression-free survival and gadolinium-enhanced magnetic resonance imaging scans. 10, 7 and 8 patients experienced neurological improvement, stabilization and progression, respectively. The median EDSS scores observed over 1-year follow-up after transplantation (5.5-7.0) were consistently lower than the baseline (8.0). The progression-free survival rate was 74, 65 and 48% at 3, 6 and 9 years post-transplant. 58% cases (7/12) had active lesions at baseline and all turned to inactive status in the years of follow-up. 25% cases (3/12) experienced progression after transplantation but had no active lesions in MRI over the whole follow-up period. 17% cases (2/12) without active lesions at baseline progressed active lesions in MRI. The major early toxicity resulted in fever and late toxicity caused transplantation-related mortality due to severe pneumonia and varicella-zoster virus hepatitis, respectively. AHSCT is a feasible treatment for severe MS and its long-term efficacy is favorable.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Esclerose Múltipla/cirurgia , Adolescente , Adulto , Antígenos CD34/metabolismo , China , Avaliação da Deficiência , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Exame Neurológico , Timócitos/metabolismo , Adulto Jovem
15.
Med Oncol ; 28(3): 822-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20373054

RESUMO

Randomized controlled trials (RCTs) have reported conflicting results on the impact of high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT) as the first-line treatment for patients with aggressive non-Hodgkin lymphoma (NHL). We performed a systematic meta-analysis to assess the efficacy of HDCT compared to conventional chemotherapy in patients with aggressive NHL with regard to overall survival (OS) at 3 years. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 11/2008) searches. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random effect model. Fourteen RCTs were identified that were published in full text and included a total of 2,413 patients. There was evidence that HDCT showed decreased OS (HR 1.20, 95% CI 1.05-1.37, P=0.006) at 3 years when compared with conventional chemotherapy. The variation in OS probabilities between studies was not statistically significant (test for heterogeneity, Q=10.14, df=13, P=0.683). Thus, our meta-analysis showed that HDCT in aggressive non-Hodgkin lymphoma had decreased overall survival outcome compared with conventional chemotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Terapia Combinada , Humanos , Transplante Autólogo
16.
Acta Haematol ; 124(2): 61-71, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20616541

RESUMO

BACKGROUND: For those patients who are not candidates for allogeneic stem cell transplantation (SCT) or who do not have an HLA-matched donor, it is unclear whether consolidation therapy with autologous SCT results in a survival benefit compared with further intensive post-remission non-myeloablative chemotherapy or no further therapy. METHODS: A meta-analysis evaluating autologous SCT versus further chemotherapy or no treatment for acute myeloid leukemia (AML) in first complete remission (CR1) was completed. The search used the following combined search terms in Medline, Embase, the Cochrane Controlled Trials Register, the Cochrane Library, the Web of Science and the China National Knowledge Infrastructure. RESULTS: Overall, 13 studies of 12 randomized controlled trials were identified. Four studies were in pediatric patients and 9 were in adults. For adults, AML in CR1 compared with non-SCT, lower relapse and higher transplantation-related mortality were associated with autologous SCT, a significant disease-free survival benefit of autologous SCT was documented, and there was no difference in overall survival when studies were pooled. For pediatric AML in CR1, there were no differences in relapse, transplantation-related mortality, disease-free survival and overall survival. Significantly less survival from relapse impairment was found for autologous SCT. CONCLUSION: Our results support the conclusion that autologous SCT should not be considered as the first-line post-remission therapy for AML patients in CR1.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Fatores de Risco , Prevenção Secundária , Transplante Autólogo
17.
Zhonghua Nei Ke Za Zhi ; 49(3): 213-6, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20450652

RESUMO

OBJECTIVE: To explore the profiles of Th1, Th2, Th17 and Regulatory T (Treg) cells in patients with chronic idiopathic thrombocytopenic purpura (ITP). METHODS: Samples of peripheral blood were collected from 35 chronic ITP patients (21 in an active stage group, 5 in a non-remission stage group, 9 in a remission stage group) and also from 18 healthy subjects. Flow cytometry was used to measure the intracellular cytokines interferon (IFN)gamma, interleukin (IL)-4 and IL-17 so as to identify the Th1, Th2 and IL-17 cells. Treg cells were identified with CD(4)(+) CD(25)(+) Foxp3(+) cells and uncultured peripheral blood was used to measure the CD(4)(+) CD(+)(25) Foxp3(+) cells with flow cytometry. The concentrations of IFNgamma, IL-4, IL-17 and IL-10 in plasma specimens were detected with ELISA method and its correlation with peripheral platelets counts and megakaryocytes number was analyzed, respectively. RESULTS: There were no statistically significant differences between any two of the three groups for the percentage of Th1 cells, Th17 cells and Th1/Th17 ratio. The percentage of Th2 cells was (1.01 +/- 0.88)% in active stage and (1.22 +/- 1.04)% in non-remission stage, being significantly decreased than those in remission stage (1.93 +/- 1.04)% (P < 0.05) and the controls (1.86 +/- 0.59)% (P < 0.05). Th1/Th2 ratio was 15.04 +/- 9.67 in active stage, 11.65 +/- 9.32 in non-remission stage, which were significantly higher than those in remission stage (7.17 +/- 5.38, P < 0.05) and the controls (7.02 +/- 3.01, P < 0.05). The percentage of Treg cells was (0.89 +/- 0.58)% in active stage and (1.46 +/- 1.27)% in non-remission stage, being significantly decreased than those in remission stage (6.41 +/- 1.86)% (P < 0.01) and the control (5.73 +/- 0.71)% (P < 0.01). There was no statistic difference between any two of the three groups for plasma IFNgamma and IL-17 level. The plasma IL-4 level was (2.25 +/- 2.05) ng/L in active stage and (2.33 +/- 2.14) ng/L in non-remission stage, being significantly decreased than those in remission stage (6.00 +/- 4.57) ng/L (P < 0.05) and the controls (5.54 +/- 4.00) ng/L (P < 0.05). The plasma IL-10 level was (5.07 +/- 4.10) ng/L in active stage and (5.66 +/- 4.35) ng/L in non-remission stage, being significantly decreased than those in remission stage (10.92 +/- 6.17) ng/L (P < 0.01) and the controls (14.21 +/- 7.31) ng/L (P < 0.01). The plasma level of IL-10 in patients in active stage was positively related to the platelet counts (r = 0.16, P = 0.03). CONCLUSION: Deficiency of Treg cells might be one of mechanisms that cause immune regulation dysfunction in chronic ITP. Th17 cells might not play a role in the development of chronic ITP.


Assuntos
Púrpura Trombocitopênica Idiopática/metabolismo , Linfócitos T Reguladores/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/imunologia , Células Th1/metabolismo , Células Th2/metabolismo , Adulto Jovem
18.
Leuk Res ; 34(12): 1596-600, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20409583

RESUMO

To date, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) C677T and childhood acute lymphoblastic leukemia have provided either controversial or inconclusive results. To clarify the effect of MTHFR C677T on the risk of childhood acute lymphoblastic leukemia, a meta-analysis of all case-control observational studies was performed. Heterogeneity (I(2)=65%, P<0.0001) for C677T among the studies was extreme. The random effects (RE) model showed that the 677T allele was not associated with a decreased susceptibility risk of childhood acute lymphoblastic leukemia compared with the C allele [OR=0.96, 95% confidence interval (CI) (0.88-1.04), P=0.34]. The contrast of homozygotes, recessive model and dominant model produced the same pattern of results as the allele contrast. Although MTHFR C677T was associated with increased risks of colorectal cancer, leukemia, and gastric cancer, our pooled data suggest no evidence for a major role of MTHFR C677T in the carcinogenesis of childhood acute lymphoblastic leukemia.


Assuntos
Alelos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Modelos Biológicos , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Neoplasias Colorretais/genética , Feminino , Homozigoto , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Neoplasias Gástricas/genética
19.
Microsc Res Tech ; 73(11): 1067-71, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20196105

RESUMO

Molecular analyses such as fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are demanded to improve diagnostic accuracy in addition to immunohistopathology of bone marrow (BM) trephine specimens. Conventional BM embedding method needs decalcification, and its procedure may impair tissue morphology and DNA quality. Here, we report an undecalcified method by which glycol methacrylate resin is polymerized at low temperature (4°C). Using this method, BM enzyme activity and antigenic determinants are well preserved, and moreover, DNA extracted from plastic embedding sections is suitable for PCR amplification and sequencing, FISH analysis can be well done because of the DNA integrity of BM sections. If working with BM trephine specimen, our protocol offers the possibility to combine superior morphology with modern molecular analysis.


Assuntos
Medula Óssea/química , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente/métodos , Metacrilatos/química , Reação em Cadeia da Polimerase/métodos , Inclusão do Tecido/métodos , Anticorpos Monoclonais/metabolismo , Antígenos CD34/química , Antígenos CD34/metabolismo , Medula Óssea/metabolismo , Medula Óssea/ultraestrutura , DNA/química , DNA/isolamento & purificação , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Janus Quinase 2/química , Janus Quinase 2/metabolismo , Leucemia , Polimorfismo de Fragmento de Restrição
20.
Leuk Res ; 34(8): 1018-22, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20031212

RESUMO

The effect of unrelated donor bone marrow transplantation (UBMT) and unrelated donor cord blood transplantation (UCBT) on the outcome of patients with hematological diseases remains controversial. We conducted a meta-analysis using data from controlled clinical trials comparing UCBT to UBMT in patients undergoing hematopoietic stem cell transplantation. Pooled comparisons of studies of UCBT and UBMT in children found that the incidence of chronic graft-versus-host disease (GVHD) was lower with UCBT (relative risk [RR]=0.41; 95% confidence interval [CI] (0.25, 0.68)), and the incidence of grades II-IV aGVHD was also significantly different (RR=0.69; 95% CI (0.55, 0.86)). The incidence of relapse was also lower with UCBT (RR=0.72; 95% CI (0.59, 0.87)). There was no difference in OS in children when studies were pooled (Hazard ratio [HR]=1.25; 95% CI (0.87, 1.78)). For adults, OS (HR=1.26; 95% CI (1.13, 1.40)) was statistically different. Thus, UCBT led to inferior outcomes than UBMT in adults.


Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sangue Fetal , Doença Enxerto-Hospedeiro/prevenção & controle , Adulto , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Doadores de Tecidos
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