Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
Transplant Cell Ther ; 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35609866

RESUMO

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a matched sibling donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are 2 major comparable treatments for SAA. Because the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin or porcine-antilymphocyte globulin, cyclosporin plus eltrombopag. The results suggested that patients treated with MSD-HSCT or IST/EPAG had similar overall survival (OS) rates exceeding 95% (P = .97). However, the event-free survival rate (EFS) of IST/EPAG (71.0%) was significantly lower than that of MSD-HSCT (89.6%), P = .04. Subgroup analysis indicated that the OS of the MSD-HSCT group was superior to that of the IST/EPAG group (100% versus 85.7%, P = .04) among those with very severe aplastic anemia (VSAA). Both the complete response rate (CR) and overall response rate (OR) with MSD-HSCT were significantly higher than those with IST/EPAG (CR: 79.2% versus 15.7%, P < .001; OR: 97.9% versus 72.6%, P = .001). In conclusion, IST/EPAG or MSD-HSCT treatment achieves an equally high OS in SAA, but MSD-HSCT leads to a better OS in patients with VSAA and shows advantages in improving EFS and accelerating hematopoietic reconstruction in patients with SAA.

2.
Br J Haematol ; 195(5): 722-730, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34405393

RESUMO

Despite the high cure probability for acute promyelocytic leukaemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. We retrospectively analysed 212 patients who were diagnosed with non-high-risk APL and received all-trans retinoic acid (ATRA) plus arsenic as front-line therapy at Peking University Institute of Hematology from February 2014 to December 2018. A total of 176 patients (83%) received oral arsenic (realgar-indigo naturalis formula) plus ATRA, 36 patients (17%) received arsenic trioxide plus ATRA and 203 patients were evaluable for relapse. After a median (range) follow-up of 53·6 (24·3-85·4) months, two patients had molecular relapse and eight had haematological relapse. A promyelocytic leukaemia/retinoic acid receptor alpha (PML-RARA) transcript level of ≥6·5% at the end of induction therapy was associated with relapse (P = 0·031). The 5-year cumulative incidence of relapse, event-free survival and overall survival were 5·5%, 92·3% and 96·3% respectively. In conclusion, the present long-term follow-up study further confirmed the high cure probability of ATRA plus oral arsenic as front-line therapy for non-high-risk APL and showed that the PML-RARA transcript level at the end of induction therapy was associated with relapse.


Assuntos
Antineoplásicos/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Tretinoína/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Humanos , Quimioterapia de Indução , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
3.
Leuk Lymphoma ; 62(12): 2949-2956, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34196252

RESUMO

To evaluate the efficacy of interferon-α (IFN-α) as maintenance therapy in patients with favorable-risk acute myeloid leukemia (AML), this retrospective study enrolled 84 patients with favorable-risk AML: 42 patients who received IFN-α maintenance therapy and 42 patients who did not (control). The median follow-up time and duration of IFN-α treatment was 26 (6-54) months and 18 (2-24) months, respectively. The 4-year estimated relapse-free survival (RFS) after the last consolidation chemotherapy was 86.8% (95% confidence interval (CI), 75.8-97.8%) in the IFN-α group and 55.7% (95% CI, 37.2-74.3%) in the control group (p=.007). The 4-year estimated overall survival was 94.4% (95% CI, 86.8-102%) and 76.4% (95% CI, 61.9-90.9%) in IFN-α and control groups, respectively (p=.040). The Cox regression analysis showed that IFN-α treatment was the only independent factor affecting RFS (p=.004). Maintenance therapy with IFN-α may prevent relapse in favorable-risk AML after consolidation chemotherapy.


Assuntos
Interferon-alfa , Leucemia Mieloide Aguda , Quimioterapia de Consolidação , Intervalo Livre de Doença , Humanos , Interferon-alfa/uso terapêutico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva , Estudos Retrospectivos
5.
Leuk Lymphoma ; 60(9): 2181-2189, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30773106

RESUMO

Acute myeloid leukemia (AML) patients with biallelic CEBPA (bi CEBPA) mutations are considered prognostically favorable, but 38-58% of them still relapse. Therefore, recognizing patients with a high risk of relapse is important. We retrospectively analyzed 83 bi CEBPA AML. Minimal residual disease (MRD) was detected by multiparameter flow cytometry (MFC). Patients with MRD positivity during consolidation chemotherapy had inferior 3-year CIR (55% vs. 36.7%; p = .037) and RFS (45% vs. 63.3%; p = .037) than those with MRD negativity. In patients with adverse cytogenetics, FLT3-ITD or MRD positivity, allogeneic hematopoietic stem cell transplantation (allo-HSCT) achieved superior 3-year CIR (0% vs. 52.8%; p = .006) and RFS (88.9% vs. 47.2%; p = .027) than did consolidation chemotherapy. Consolidation chemotherapy maintained a relatively favorable outcome (3-year CIR, 29%; 3-year RFS, 71%) in patients with intermediate cytogenetics, negative FLT3-ITD, and MRD negativity. Therefore, MFC-MRD could predict relapse and was complementary to genetics for risk stratification treatment in bi CEBPA AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Estimuladoras de Ligação a CCAAT/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/diagnóstico , Adolescente , Adulto , Idoso , Alelos , Quimioterapia de Consolidação , Análise Citogenética , Intervalo Livre de Doença , Feminino , Citometria de Fluxo/métodos , Testes Genéticos , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Neoplasia Residual , Prognóstico , Estudos Retrospectivos , Medição de Risco , Transplante Homólogo , Adulto Jovem
6.
Bone Marrow Transplant ; 54(8): 1319-1326, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30670825

RESUMO

Our study aimed to compare treatment outcomes between hematopoietic stem cell transplantation (HSCT) from haploidentical donors (HID) and immunosuppressive therapy (IST) in adults with acquired severe aplastic anemia (SAA). The medical records of 113 SAA adults who received IST, including rabbit ATG and cyclosporin (N = 37), or HID HSCT (N = 76) within 6 months of diagnosis at two institutions were retrospectively reviewed. Estimated 8-year overall survival (OS) was comparable between the IST and HID HSCT groups (75.6 vs. 83.7%, respectively, P = 0.328), but failure free survival (FFS) was significantly lower in IST group than HID HSCT group (38.5 vs. 83.7%, respectively, P = 0.001). Furthermore, a significant improvement in FFS was observed with HSCT over IST in patients under 40 years old. At the last follow-up, patients in HSCT group achieved better Karnofsky Performance Status (KPS) than those in IST group (100 [20-100] vs. 90 [20-100], P = 0.002). In terms of blood count, 83.1% (54/65) of patients in HSCT group showed complete recovery compared to only 38.2% (13/34) in IST group (P < 0.001). These data suggest that HID HSCT could be an effective alternative treatment option for SAA adults, and additional prospective studies are necessary.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Anemia Aplástica/mortalidade , Feminino , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
7.
Clin Cancer Res ; 25(6): 1737-1748, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30478089

RESUMO

PURPOSE: Although myeloablative HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. PATIENTS AND METHODS: In this prospective trial, among 443 consecutive patients ages 16-60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n = 69) or underwent haplo-HSCT (n = 78). RESULTS: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; P = 0.0004 and 80.8% vs. 53.5%; P = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163-0.793; P = 0.011], OS (HR 0.361; 95% CI, 0.156-0.832; P = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057-0.459; P = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. CONCLUSIONS: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/administração & dosagem , Recidiva Local de Neoplasia/epidemiologia , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro , Humanos , Incidência , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estudos Prospectivos , Fatores de Risco , Irmãos , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adulto Jovem
9.
Med Sci Monit ; 24: 758-767, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29408852

RESUMO

BACKGROUND Acute myeloid leukemia with intermediate cytogenetic risk (ICR-AML) needs to be stratified. The abnormal gene expression might be prognostic, and its cutoff value for patient grouping is pivotal. MATERIAL AND METHODS Ecotropic viral integration site 1 (EVI1) transcripts were assessed in 191 adult ICR-AML patients at diagnosis who received chemotherapy only. MLL-PTD, WT1 transcript levels, FLT3-ITD, and NPM1 mutations were simultaneously evaluated, and 27 normal bone marrow samples were tested to define normal threshold. RESULTS The normal upper limit of EVI1 transcript levels was 8.0%. Receiver operating characteristic curve analysis showed that 1.0% (a 0.9-log reduction from the normal limit) was the EVI1 optimal cutoff value for significantly differentiating relapse (P=0.049). A total of 23 patients (12%) had EVI1 levels ≥1.0%. EVI1 ≥1.0% had no effect on CR achievement, whereas it was significantly associated with lower 2-year relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS) rates in the entire cohort (P=0.0003, 0.0017, and 0.0009, respectively), patients with normal karyotypes (P=0.0032, 0.0047, and 0.0007, respectively), and FLT3-ITD (-) patients (all P<0.0001). Multivariate analysis showed that EVI1 ≥1.0% was an independent adverse prognostic factor for RFS, DFS, and OS in the entire cohort. In addition, patients with EVI1 transcript levels between 1.0% and 8.0% had 2-year RFS rates similar to those with EVI1 ≥8.0%, and they both had significantly lower RFS rates than those with EVI1 <1.0% (P=0.0005 and 0.027). CONCLUSIONS High EVI1 expression predicts poor outcome in ICR-AML patients receiving chemotherapy. The optimal cutoff value for patient stratification is different from the normal limit.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Proteína do Locus do Complexo MDS1 e EVI1/genética , Adolescente , Adulto , Idoso , Medula Óssea/patologia , Estudos de Coortes , Citogenética , Intervalo Livre de Doença , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Proteína do Locus do Complexo MDS1 e EVI1/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
10.
Leuk Lymphoma ; 59(4): 967-972, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28745571

RESUMO

This study aimed to analyze the effects of the initial MLL-partial tandem duplication (PTD) expression levels on clinical outcomes in 36 MLL-PTD-positive acute myeloid leukemia (AML) patients between 2014 and 2016. ROC curves showed 1.0% MLL-PTD as the optimal diagnostic cutoff for complete remission (CR). Nineteen and 17 cases had MLL-PTD <1.0% (low-level group) and ≥1.0% (high-level group), respectively. The FAB type distribution (M2 incidence, 100% vs. 53%, p = .003) and double-CEBPA-mutation incidence (37% vs. 0%, p = .008) significantly differed between the groups, as did the CR rates after the first (78.9% vs. 35.3%, p = .008) and second chemotherapies (84.2% vs. 47.1%, p = .001). High MLL-PTD level was the only independent factor affecting the CR rate (odds ratio = 0.16, p = .024). The 24-month overall survival was significantly lower in the high-level group (52.6% vs. 29.4%, p = .043). In conclusion, AML patients with high initial MLL-PTD levels have lower induction CR and survival rates.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Duplicação Gênica , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Sequências de Repetição em Tandem/genética , Adulto , Idoso , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
11.
Leuk Res ; 65: 14-19, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29232592

RESUMO

The aim of our study was to evaluate the impact of oral arsenic (the realgar-indigo naturalis formula, RIF) and all-trans retinoic acid (ATRA) on coagulopathy in acute promyelocytic leukemia (APL) compared with intravenous arsenic trioxide (ATO) and ATRA during induction. Mitoxantrone was added to all the patients at a dose of 1.4mg/m2 per day for 5-7 days. D-dimer levels, prothrombin time (PT), fibrinogen (Fbg) levels and the platelet count were comparably analyzed among 83 newly diagnosed APL patients treated with RIF (n=45) or with ATO (n=38). Since induction therapy with RIF and ATRA, the median levels of Fbg, PT and platelets were recovered to the normal range within 4days, 10days and 28days, respectively. The last day of platelet and plasma transfusion was day 12 (range: 0-24 days) and day 3 (range: 0-27 days), respectively. Among the 42 patients with a disseminated intravascular coagulation (DIC) score=4, the consumption of transfused platelets was less in the RIF group than that in the ATO group (P=0.037). In the 17 patients with a DIC score <4, prompt recovery of Fbg levels (P=0.028) was observed in the RIF group compared with that in the ATO group (P=0.401). RIF and ATO showed similar effects on the recovery of coagulopathy in APL patients. RIF had a potential beneficial effect in accelerating the recovery of thrombocytopenia and hypofibrinogenemia for subclinical DIC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Coagulação Intravascular Disseminada/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Administração Oral , Adolescente , Adulto , Trióxido de Arsênio/administração & dosagem , Transfusão de Sangue , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/fisiopatologia , Coagulação Intravascular Disseminada/terapia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Leucemia Promielocítica Aguda/sangue , Masculino , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Transfusão de Plaquetas , Estudos Retrospectivos , Tretinoína/administração & dosagem , Adulto Jovem
12.
Biol Blood Marrow Transplant ; 24(4): 741-750, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29247779

RESUMO

Here we compare outcomes between the tyrosine kinase inhibitors (TKIs) plus chemotherapy regimen and allogeneic hematopoietic stem cell transplantation (transplantation cohort) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and explore factors associated with prognosis. Data from 145 Ph+ ALL patients were analyzed retrospectively. Patients were treated with imatinib plus chemotherapy and then transplantation or continuous TKIs with chemotherapy based on patient preference. A total of 145 Ph+ ALL patients were recruited for this study (median age, 37 years; range, 14 to 65). Among these patients, 81 were men (55.9%) and 86 underwent IKZF1 detection, which identified 59 patients (68.6%) with IKZF1 deletions. After treatment 136 patients (95.8%) achieved complete remission (CR) eventually. With a median follow-up of 33 months (range, 4 to 114) for CR patients, 77 patients (57.9%) underwent transplantation and 56 (42.1%) received continuous TKIs with chemotherapy. At the 4-year follow-up the cumulative incidence of relapse (CIR), disease-free survival (DFS), and overall survival (OS) were 29.4% (95% confidence interval [CI], 24.9% to 34.4%), 60.9% (95% CI, 56.5% to 65.3%), and 69.2% (95% CI, 65.1% to 73.3%), respectively. Multivariate analysis showed that WBC counts < 30 × 109/L at diagnosis (hazard ratio [HR], 4.2; 95% CI, 1.9 to 9.2; P < .001; HR, 2.6; 95% CI, 1.4 to 4.9; P = .003; HR, 2.7; 95% CI, 1.4 to 5.4; P = .003), 3-log reduction of BCR-ABL levels from baseline after 2 consolidation cycles (HR, 4.4; 95% CI, 1.9 to 9.9; P < .001; HR, 3.1; 95% CI, 1.7 to 5.9; P < .001; HR, 3.5; 95% CI, 1.9 to 8.7; P = .001; defined as "minimal residual disease low level"), and transplantation (HR, 5.0; 95% CI, 2.2 to 11.2; P < .001; HR, 3.3; 95% CI, 1.7 to 6.4; P < .001; HR, 4.1; 95% CI, 1.9 to 8.7; P < .001) were the favorable factors of CIR, DFS, and OS. According to the first 2 risk factors, CR patients were divided into 3 groups: low risk (no factor, n = 42, 31.6%), intermediate risk (1 factor, n = 73, 54.9%), and high risk (2 factors, n = 18, 13.5%). In the low-risk group at the 4-year follow up no significant difference existed between the transplant and nontransplant arms for the probabilities of CIR (8.5% versus 7.7%, P = .671), DFS (88.2% versus 83.9%, P = .426), and OS (96.6% versus 83.3%, P = .128). In the intermediate- and high-risk groups at the 4-year follow-up, CIR (23.6% versus 36.9%, P = .017; 37.5% versus 100.0%, P <.001), DFS (62.4% versus 43.8%, P = .048; 56.2% versus 0%, P <.001), and OS (76.1% versus 47.7%, P = .037; 51.4% versus 6.3%, P = .001) rates were significantly better in the transplant arm than in the nontransplant arm. In surviving patients of the low-risk group, no difference in complete molecular response (CMR) rates (85.7% versus 72.7%, P = .379) between the transplant and nontransplant arms was found. However, in the intermediate-risk group the proportion of CMR was significantly higher in the transplant arm than in the nontransplant arm (82.8% versus 42.9%, P = .006). In the high-risk group 4 of 7 transplant patients (57.1%) were in CMR, and no patients survived in the nontransplant arm. Allogeneic hematopoietic stem cell transplantation confers significant survival advantages for Ph+ ALL patients compared with TKIs plus chemotherapy, especially in intermediate- and high-risk patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mesilato de Imatinib/administração & dosagem , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases/administração & dosagem , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Taxa de Sobrevida
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(6): 1733-1737, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29262907

RESUMO

OBJECTIVE: To investigate the effects of Cyclin A1 on the proliferation of SKM-1 cells and its underlying role in myelodysplastic syndrome (MDS). METHODS: Cyclin A1 was knocked down with its small interfering RNA (siRNA). The efficiency of siRNA transfection was measured by Western blot and RT-PCR. Then the proliferation of SKM-1 cells and the expression of CDK2,RUNX1 and SRSF2 with and without knockdown of Cyclin A1 recorded and analysed respectively. RESULTS: Cyclin A1 was knocked down by siRNA after transfected for 48 h. The kncokdown of Cyclin A1 inhibited the proliferation of SKM-1 cells and down-regulated the expression of CDK2, RUNX1 and SRSF2, and these effects were at least partially mediated through RUNX1 and SRSF2 signaling pathway. CONCLUSION: Cyclin A1 plays an important role in the proliferation of SKM-1 cells. These findings provide new insights into the pathogenesis of MDS, and it may be a potential target in the treatment of MDS.


Assuntos
Proliferação de Células , Ciclina A1/metabolismo , Síndromes Mielodisplásicas/metabolismo , RNA Interferente Pequeno , Apoptose , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Síndromes Mielodisplásicas/patologia
14.
Leuk Res ; 61: 84-88, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28934679

RESUMO

OBJECTIVE: We aimed to compare the kinetics of white blood cell (WBC) and explore predictive factors of leukocytosis in non-high-risk acute promyelocytic leukemia (APL), with oral arsenic plus all-trans retinoic acid (ATRA) or intravenous arsenic trioxide (ATO) plus ATRA as a first-line treatment. METHODS: The absolute count, doubling time and peak time of WBC were analyzed in 64 newly diagnosed non-high-risk APL patients who were treated with different induction regimens containing either oral Realgar-indigo naturalis formula (RIF) (n=35) or ATO (n=29). The end points were the dynamic changes of the WBC counts during induction. The time points started at day 1 and were selected over 3-day intervals for 28days. RESULTS: Among the 64 included patients, the median initial and peak WBC counts were 1.78×109/L (range 0.31-9.89) and 12.16×109/L (range 1.56-80.01), respectively. The incidence of differentiation syndrome was 9.38%. The dynamic changes in leukocytosis showed a single peak wave in all the patients, and the median time to peak was 10 (range 2-26) days. A higher WBC count was observed in the RIF group than in the ATO group after 10days of treatment (9.22×109/L vs. 4.10×109/L, p=0.015). Patients with the peak WBC count >10×109/L had a shorter WBC doubling time compared to patients with a lower peak WBC (RIF group 4days vs. 7days, p=0.001; ATO group 4.5days vs. 23days, p=0.002). Univariate and multivariable analyses showed that the doubling time of WBC is an independent factor for the peak WBC count. CONCLUSION: Different kinetics of WBC proliferation were observed during induction with oral arsenic plus ATRA and ATO plus ATRA. The doubling time of WBC is an important independent factor for predicting the peak WBC count.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Arsenicais/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Leucemia Promielocítica Aguda/sangue , Leucócitos/efeitos dos fármacos , Leucocitose/induzido quimicamente , Óxidos/efeitos adversos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Trióxido de Arsênio , Arsenicais/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Óxidos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Tretinoína/administração & dosagem , Adulto Jovem
15.
Leuk Res ; 44: 40-4, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26994850

RESUMO

Homoharringtonine combined aclarubicin and cytarabine (HAA) has been demonstrated to achieve a high remission rate and provide a survival advantage in acute myeloid leukemia (AML). To investigate whether HAA is an ideal induction regimen for t(8;21)AML, we retrospectively analyzed the data of 140 patients from the last 8 years in our center. When achieving complete remission (CR), the post-remission treatment was administered as a minimal residual disease-directed risk-stratification treatment protocol. The RUNX1/RUNX1T1 transcript level was assessed by RT-qPCR. The last follow-up was conducted in October 2015. In total, thirty patients received an HAA regimen as the induction treatment. The CR rate after one cycle of the HAA regimen was 93.3% (28/30). One patient achieved partial remission, and one had no response. No patients died during induction treatment. The median fold decrease of the RUNX1/RUNX1T1 transcript level was 200 (1-358000), and 16.7% (5/30) patients achieved >3 log decrease after one cycle of the HAA regimen. The estimated 4-year disease-free survival and overall survival were 89.9% and 90.8%, respectively. We concluded that the HAA regimen is highly effective as the first course of induction therapy for t(8;21) AML, and this needs to be confirmed in a large population in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomos Humanos Par 21/genética , Cromossomos Humanos Par 8/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Translocação Genética/genética , Aclarubicina/administração & dosagem , Adolescente , Adulto , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Citarabina/administração & dosagem , Feminino , Seguimentos , Harringtoninas/administração & dosagem , Mepesuccinato de Omacetaxina , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Proteínas de Fusão Oncogênica/genética , Prognóstico , RNA Mensageiro/genética , Proteína 1 Parceira de Translocação de RUNX1 , Reação em Cadeia da Polimerase em Tempo Real , Indução de Remissão , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Adulto Jovem
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(2): 273-8, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23628015

RESUMO

This study was purposed to detect the methylation status in promoter region of RUNX2 gene and its expression in cell lines and patients with HOX11(+) T-cell acute lymphoblastic leukemia (T-ALL) and to explore the relationship between the expression level of RUNX2 gene and methylation of CpG island in its promoter region. The methylation pattem in promoter region of RUNX2 gene was detected with bisulfite sequencing PCR, DNA methylation immunoprecipitation technique and promoter oligonucleotide microarray analysis and the expression levels of RUNX2 mRNA was detected with RT-PCR in 3 T-ALL cell lines (sil-ALL, DND41 and RPMI), as well as in 75 clinic bone marrow samples including 38 de novo T-ALL patients, 29 complete remission T-ALL patients and 8 normal samples. The results showed that there were hypermethylation of CpG island in promoter region of RUNX2 gene in patients with highly expressing HOX11(+) T-ALL. The methylation rate of the promoter CpG islands of RUNX2 gene in HOX11(+) T-ALL (78.9%) was significantly higher than that in HOX11(-) T-ALL (36.8%) (P < 0.01). The expression of RUNX2 in HOX11(+) cell lines was significantly lower than that in HOX11(-) cell lines, and the expression level of RUNX2 in the HOX11(+) T-ALL patients (0.581 ± 0.257) was significantly lower than that in HOX11(-) T-ALL patients (0.835 ± 0.317). The relationship between RUNX2 and HOX11 mRNA expression level showed a negative correlation (rs = -0.378, P < 0.01). The expression levels of RUNX2 gene negatively correlated with the methylation of CpG island in its promoter region (rs = -0.419, P < 0.01). It is concluded that HOX11 is a negative regulator of RUNX2 gene and the expression of RUNX2 is down regulated or even lost by promoter methylation in T-ALL, which demonstrate a better event-free survival and a marked trend for longer overall survival for HOX11-high T-ALLs. The expression and methylation level of RUNX2 gene may have some significance in evaluating the curative effect of T-ALL. The abnormal expression of RUNX2 may be a prognostic marker in T-ALL patients.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/genética , Ilhas de CpG/genética , Metilação de DNA , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Adulto , Estudos de Casos e Controles , Linhagem Celular Tumoral , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Feminino , Proteínas de Homeodomínio/genética , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Adulto Jovem
18.
Zhonghua Yi Xue Za Zhi ; 93(48): 3835-40, 2013 Dec 24.
Artigo em Chinês | MEDLINE | ID: mdl-24548444

RESUMO

OBJECTIVE: To detect the status of methylation in promoter region of MEIS1 gene and its expression in cell lines and patients with HOX11(+) T-cell acute lymphoblastic leukemia (T-ALL) and explore the relationship between the expression level of MEIS1 gene and methylation of CpG island in promoter region. METHODS: The methylation pattern in MEIS1 gene was detected with bisulfite sequencing PCR, DNA methylation immunoprecipitation and promoter oligonucleotide microarray. And the expression level of MEIS1 mRNA was detected with reverse transcription PCR in 3 T-ALL cell lines: sil-ALL, DND41 and RPMI as well as in 75 clinical bone marrow samples including 38 de novo T-ALL patients, 29 complete remission T-ALL patients and 8 normal samples from January 2009 to December 2011. RESULTS: The expressions of HOX11 mRNA in the patients were classified into high expression (HOX11(+)) groups (n = 14) and low expression (HOX11(-)) groups (n = 24) . There was hypermethylation of CpG island in promoter region of MEIS1 gene in patients with HOX11(+) T-ALL. The methylation rate of promoter CpG islands of MEIS1 gene in HOX11(+) T-ALL (76.8%) was significantly higher than that of HOX11(-) T-ALL (29.5%) (P < 0.01). The expression MEIS1 in complete remission T-ALL patients and normal samples was significantly lower than that in de novo T-ALL patients (both P < 0.05) . The expression MEIS1 in HOX11(+) cell lines was significantly lower than that in HOX11(-) cell lines (0.392 ± 0.226,0.378 ± 0.317 vs 1.059 ± 0.533, both P < 0.05) and the expression level of MEIS1 in HOX11(+) T-ALL patients (0.462 ± 0.281) significantly lower than that in HOX11(-) T-ALL patients (0.916 ± 0.437) (P < 0.01). The relationship between MEIS1 and HOX11 mRNA expression level had a negative correlation (rs = -0.416, P < 0.01) . The expression level of MEIS1 gene was negatively correlated with the methylation of CpG island in promoter region in T-ALL (rs = -0.383, P < 0.01) . CONCLUSIONS: The expression of MEIS1 becomes down-regulated or even lost by promoter methylation in T-ALL. HOX11 maybe a negative regulator of MEIS1 gene.


Assuntos
Ilhas de CpG , Metilação de DNA , Genes Homeobox , Proteínas de Homeodomínio/genética , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Adulto , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Meis1 , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/metabolismo , Adulto Jovem
19.
Zhonghua Yi Xue Za Zhi ; 89(1): 41-4, 2009 Jan 06.
Artigo em Chinês | MEDLINE | ID: mdl-19489243

RESUMO

OBJECTIVE: To evaluate the effect and safety of piperacillin/tazobactam on neutropenic febrile patients with Malignant Hematopathy. METHODS: 218 patients with malignant hematopathy complicated by infectious fever, 162 (74.31%) with fever of unknown origin (FUO), 33 (15.14%) with clinically defined infection (CDI), and 23 (10.55%) with microbiologically defined infection (MDI), underwent intravenous drip of piperacillin/tazobactam at the dose of 4.5 g for 30 min every 8 hours till 4 - 5 d after the temperature returned to normal or neutropenia was relieved. Twenty hours before and after treatment blood routine, blood biochemical and electrolytes, and bacteriological examination, chest X-ray examination were conducted. The changes of symptoms and signs were observed. RESULTS: The total effective rate was 65.60%, the bacteria clearance rate was 71.43%, and the adverse reaction rate was 5.04%. The average defervescence time was (2.5 +/- 1.2) days, and the duration of antibiotic therapy was (9.4 +/- 8.1) days. There were not significant differences in the curative effect and defervescence time between the patients undergoing chemotherapy and those undergoing hematopoietic stem cell transplantation (chi2 = 2.058, P > 0.05, and t = 1.892, P > 0.05). After the piperacillin/tazobactam treatment the white blood cell count and absolute neutrophile granulocyte count of the patients significantly increased (t = 4.092, P < 0.01; t = 4.248, P < 0.01). However, the hepatic and renal functions did not change obviously after treatment. CONCLUSIONS: Piperacillin/tazobactam therapy is effective and safe empirical antibacterial therapy in febrile neutropenic patients with hematological malignancies.


Assuntos
Antibacterianos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Neutropenia/tratamento farmacológico , Ácido Penicilânico/análogos & derivados , Piperacilina/uso terapêutico , Adulto , Antibacterianos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/uso terapêutico , Piperacilina/efeitos adversos , Estudos Prospectivos , Tazobactam , Resultado do Tratamento
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 17(2): 377-81, 2009 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-19379570

RESUMO

The purpose of this study was to evaluate the expression of cyclin A1 mRNA in patients with myelodysplastic syndrome (MDS) and its clinical significance. The expression of cyclin A1, cdk2 and p21(cip1) mRNA in the bone marrow from 56 patients with MDS and 10 normal control were measured by using reverse transcription polymerase chain reaction (RT-PCR) technique. The results indicated that the positive rate and the expression level of cyclin A1 in MDS patients (69.64%; 0.964 +/- 1.879) were significantly higher than those in normal control (0%; 0.012 +/- 0.014) (p < 0.01). Among de-novo MDS patients, the expression level of cyclin A1 mRNA in the MDS-RAEB group (1.895 +/- 1.769) was higher than that in MDS-RA group (0.629 +/- 1.583) (p < 0.01). The expression level of cyclin A1 mRNA in post-treatment group was significantly lower than that in prior-treatment group (p < 0.01). It is concluded that the mRNA expression of cyclin A1 in MDS patients is higher than that in normal control, the abnormal expression of cyclin A1 may be used as a prognostic marker in MDS patients.


Assuntos
Ciclina A1/metabolismo , Síndromes Mielodisplásicas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ciclina A1/genética , Feminino , Células HL-60 , Humanos , Células K562 , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...