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1.
Ann Transplant ; 24: 328-340, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31171762

RESUMO

BACKGROUND Allogeneic transplantation remains one of the best therapies for high-risk acute myeloid leukemia (HR-AML). MATERIAL AND METHODS This study retrospectively analyzed 126 patients with HR-AML after allogeneic hematopoietic stem cell transplantation (allo-HCST). RESULTS The disease-free survival (DFS) rates of 1 year and 3 years were 58.83% (95%CI: 50.75-68.20%) and 53.09% (95%CI: 44.59-63.22%) respectively. The cumulative relapse rates of 1 year and 3 years were 21.1% (95%CI: 14.4-28.8%) and 25.9% (95%CI: 18.1-34.5%) respectively. The cumulative incidences of III to IV acute graft-versus-host disease (aGVHD) for 100 days was 8.70% (95%CI: 4.6-14.5%). The cumulative rate of extensive chronic graft-versus-host disease (cGVHD) for 1-year was 4.1% (95%CI: 1.5-8.7%). The cumulative transplantation related mortality rate of 1 year and 3 years were 20.1% (95%CI: 13.6-27.6%) and 21.0% (95%CI: 14.3-28.6%) respectively. Univariate analysis revealed that lower overall survival was correlated with age, bacterial or fungal infection, disease status at transplantation, III-IV aGVHD, post-transplantation lymphoproliferative disorders (PTLD), white blood cell engraftment, and extramedullary involvement (P<0.05). The results of multivariate analysis were that the aforementioned factors were also related to lower overall survival except for PTLD (P<0.05). The results of univariate and multivariate analysis were that extramedullary involvement, III-IV aGVHD, and status pre-transplantation influenced DFS (P<0.05). The risk factors for relapse were status pre-transplantation and extramedullary involvement by univariate and multivariate analysis (P<0.05). CONCLUSIONS HR-AML has inferior prognosis. Our study indicated the necessity of achieving remission status prior to hematopoietic stem cell transplantation, and administration of preventive treatments on high-risk patients after hematopoietic stem cell transplantation. In addition, adequate prevention and treatment of complications are needed.

2.
Ann Transplant ; 24: 175-184, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30940797

RESUMO

BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following solid organ transplantation and allogeneic hematopoietic stem cell transplantation (Allo-HSCT), which gives rise to high mortality rates. MATERIAL AND METHODS This was a single-center retrospective analysis based on 27 patients who were diagnosed with PTLD following Allo-HSCT between January 1, 2007 and June 2018 at the Chinese PLA General Hospital. The purpose of this analysis was to investigate responses and prognostic factors of rituximab-based treatment. RESULTS Twenty-seven patients were treated with rituximab. Among them, 20 of 27 patients (74.07%) had a complete response, 2 of 27 patients (7.41%) had a partial response, 5 of 27 patients (18.52%) had no response, and 22 of 27 patients (81.48%) cleared Epstein-Barr virus (EBV) copies. There were no obvious side effects. The 1-year overall survival (OS) estimate was 46.8% (95% CI, 23.1-65.5%). Univariate analysis revealed that lower OS was correlated with Eastern Cooperative Oncology Group (ECOG) score standard (3-4), Epstein-Barr virus (EBV) viral load (≥106 copies/mL), bacteria or fungal infection, and EBV reactivation were positive after treatment with 1 or 2 doses of rituximab (P<0.05). Multivariate analysis showed that each of the following were independently associated with lower OS (P<0.05): female, ECOG score standard (3-4), and EBV reactivation were positive after treatment with 1 or 2 doses of rituximab. CONCLUSIONS Our results demonstrated that rituximab-based treatment was a safe and effective strategy for patients who were diagnosed with PTLD following Allo-HSCT. The identified prognostic factors may help to detect which PTLD patients are at a higher risk of mortality.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Rituximab/uso terapêutico , Adolescente , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Criança , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Transtornos Linfoproliferativos/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Carga Viral , Ativação Viral , Adulto Jovem
3.
Transfus Med Rev ; 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30482420

RESUMO

Controversial results exist regarding the clinical benefits of single- vs double-unit umbilical cord blood transplantation (UCBT) in patients with hematologic diseases. A systematic review was conducted to evaluate this issue. The PubMed, Embase, and Cochrane Library databases were searched up to May 2018. A total of 25 studies including 6571 recipients were identified. Although double-unit UCB contained higher doses of total nucleated cells and CD34+ cells, it offered no advantages over single-unit UCB in terms of hematologic recovery, including the rate and speed of neutrophil and platelet engraftment. Double-unit UCBT was associated with higher incidences of grades II-IV acute and extensive chronic graft-vs-host disease, accompanied by a lower relapse incidence, which may be attributed to a graft-vs-graft effect induced by double-unit UCB. However, transplant-related mortality, disease-free survival, and overall survival were comparable between single- and double-unit UCBT. Although double-unit UCBT confers no clinical advantages over single-unit UCBT, certain patients, such as those at high risk of relapse, might benefit from double-unit UCBT, a possibility that needs to be clarified in future randomized trials.

4.
Ann Hematol ; 97(10): 1941-1950, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29947972

RESUMO

A meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of mesenchymal stromal cells (MSCs) for the prophylaxis of chronic graft-versus-host disease (cGVHD) in patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Six studies involving 365 patients were included. The pooled results showed that MSCs significantly reduced the incidence of cGVHD (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.46 to 0.86, P = 0.004). Favorable prophylactic effects of MSCs on cGVHD were observed with umbilical cord-derived, high-dose, and late-infusion MSCs, while bone marrow-derived, low-dose, and coinfused MSCs did not confer beneficial prophylactic effects. In addition, MSC infusion did not increase the risk of primary disease relapse and infection (RR 1.02, 95% CI 0.70 to 1.50, P = 0.913; RR 0.89, 95% CI 0.44 to 1.81, P = 0.752; respectively). Moreover, there was an apparent trend toward increased overall survival (OS) in the MSC group compared with that in the control group (RR 1.13, 95% CI 0.98 to 1.29, P = 0.084). In conclusion, this meta-analysis demonstrated that MSC infusion is an effective and safe prophylactic strategy for cGVHD in patients with hematological malignancies undergoing allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Aloenxertos , Células da Medula Óssea , Sangue Fetal/citologia , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Incidência , Infecção/epidemiologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Especificidade de Órgãos , Recidiva , Resultado do Tratamento
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 796-801, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950222

RESUMO

OBJECTIVE: To explore the killing effect of CAR (CD138-CD28-CD3ζ)-NK cells on myeloma cells through construction of CAR(CD138-CD28-CD3)-NK cells. METHODS: The antiCD138scFv-CD28-CD3 zeta plasmid pcDNA3.1 was constructed, which then together with 3 plasmid lentiviral packaging system were transfected into 293T cells, the virus was collected. Furthermore, in order to get the stably transfected cell line, the NK92MI cell line was infected by the virus, then the positive cells were screened by puromycin. The expression of the CARNK cells were verified by RT-PCR and Western blot. At last the ability of secreting cytokine CD107a was detected by flow cytometry, and the statistical analysis was carried out to verify the anti-myeloma effect of CAR-NK cells. RESULTS: Gene fragment of the CAR(antiCD138scFv-CD28-CD3ζ) was constructed successfully by gene engineering technique in vitro, and the gene sequence was verified to be correct by sequencing. By virus packaging technology, the virus expressing the protein of the CAR was obtained. PCR and Western blot verified the expression of CAR fusion protein on the sufurce of NK cells. The cell killing experiment confirmed that the CAR-NK cells possessed the ability to secrete cytokine CD107a superior to control cells and showed the obvious killing effect on multiple myeloma cells. CONCLUSION: The CAR can be constructed in vitro, and express on NK92 cells. The CAR-NK cells can kill the multiple myeloma cells expressing CD138 antigen, thereby plays an antimyeloma effect.


Assuntos
Células Matadoras Naturais , Mieloma Múltiplo , Linhagem Celular Tumoral , Humanos , Lentivirus , Receptores de Antígenos , Receptores de Antígenos de Linfócitos T
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 153-158, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397835

RESUMO

OBJECTIVE: To establish the animal model of luciferase-transfected A20 murine B cell lymphoma, so as to provide experimental tools to explore the effect of graft versus tumor. METHODS: Luciferase- labeled A20 cells were cloned with puromycin selection. Transfected A20 cells and C57BL/6 bone marrow were inoculated into the irradiated BALB/c mice by injection in tailvein to establish the transplantation model. The bioluminescent imaging technique was used to monitor the tumor growth, and then the survival, body weight, tumor formation and pathological characteristics of target organs were observed. RESULTS: A20 cell line stably expressing luciferase gene was successfully obtained. The the bioluminicent imaging found that the tumor luminescence could be observed on day 8 of A20 cell inoculation, and the mean fluorescent intensity was increased along with the tumor growth. Compared with the BMT group, the survival rate and body weight of BMT+A20-Luc+ mice were decreased significantly. General anatomy showed the tumor mainly formed in the liver and spleen. CONCLUSION: A mouse transplantation model with luciferase- transfected A20 cells has been successfully established, thus laying a foundation for investigation of graft-versus-tumor.


Assuntos
Linfoma , Animais , Transplante de Medula Óssea , Luciferases , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
7.
Leuk Lymphoma ; 58(10): 2452-2459, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28278715

RESUMO

Central nervous system lymphoma (CNSL) presents diagnostic and prognostic challenges. The aim of this meta-analysis was to evaluate the diagnostic and prognostic value of interleukin (IL)-10 in cerebrospinal fluid (CSF) for CNSL comprehensively. PubMed and Cochrane Library databases were searched through September 2016. Four studies with 212 CNSL patients and 262 control patients were included. The pooled sensitivity and specificity of CSF IL-10 for diagnosing CNSL were 81% (95% CI: 66-91%) and 97% (95% CI: 83-100%), respectively. The summary receiver operating characteristic (SROC) curve indicated that the area under the curve was 0.95 (0.93-0.97). The ROC curve based on extracted individual data showed that the optimal cutoff value was 6.88 pg/ml. Moreover, elevated CSF IL-10 was found to be associated with shorter progression-free survival (hazard ratio: 2.89, 95% CI: 1.13-7.41, p = .027). In conclusion, our meta-analysis showed that CSF IL-10 is an effective diagnostic and prognostic biomarker for CNSL.

8.
Sci Rep ; 6: 39003, 2016 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-27991534

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired platelet production. In this study, we conducted a systematic review and meta-analysis to determine the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in primary ITP patients. Thirteen randomized controlled trials were included in this study, the pooled results of which demonstrated that TPO-RAs significantly increased platelet response (R) and durable response (DR) rates [risk ratio (RR): 2.77, 95% confidence interval (CI): 2.01-3.82, P = 5.9 × 10-10; RR: 7.52, 95% CI: 3.94-14.35, P = 9.2 × 10-10; respectively] and that TPO-RAs significantly reduced the incidences of any or severe bleeding events (RR: 0.80, 95% CI: 0.67-0.95, P = 0.013; RR: 0.52, 95% CI: 0.27-0.99, P = 0.048; respectively). Moreover, our results indicated that there was a significant reduction in the proportion of patients needing rescue medications in the TPO-RA groups compared with the control groups (RR: 0.50, 95% CI: 0.42-0.59, P = 2.0 × 10-15) and that the rates of any or severe adverse events were similar between the TPO-RA and control regimens (RR: 1.01, 95% CI: 0.92-1.10; RR: 0.74, 95% CI: 0.54-1.01; respectively). These findings demonstrate that TPO-RAs are an effective and safe second-line treatment option for primary ITP patients.


Assuntos
Plaquetas/metabolismo , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/metabolismo , Receptores de Trombopoetina/agonistas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(4): 1132-6, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27531788

RESUMO

OBJECTIVE: To explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilization on S1P5 expression in T lymphocyte subsets of allo-HSCT donors. METHODS: The peripheral blood was collected from 10 allo-hematopoietic stem cell transplantation (allo-HSCT) donors before and after mobilization with rhG-CSF for 4 days. The flow cytometry was used to detect S1P5 expression in T lymphocyte subsets. RESULTS: There was no S1P5 expression on the surface of T-lymphocytes both before and after rhG-CSF mobilization. After fixation with permeabilization agent, S1P5 expression could be detected in lymphocytes after rhG-CSF mobilization, which indicates S1P5 may be located in cells. Compared with level before rhG-CSF mobilization, S1P5 expression was significantly increased in T lymphocyte subsets after rhG-CSF mobilization, CD3(+)T cells (57.92±2.32)% vs (7.94±1.47)%(P<0.05), CD4(+)T cells (72.58±1.73)% vs (5.48±0.82)%(P<0.05), CD8(+)T cells(51.79±3.57)% vs (6.46±1.01)%(P<0.05),CD3-/CD56(+)NK cells(40.00±1.47)% vs(4.97±0.74)%(P<0.05). The up-regulated level of S1P5 expression in CD4(+)T cells was most high(P<0.05). CONCLUSION: S1P5 expression significantly increases in T lymphocyte subsets after rhG-CSF mobilization, and the up-regulated level of S1P5 expression in CD4(+)T cells is the most high.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Subpopulações de Linfócitos T , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos , Humanos , Receptores de Lisoesfingolipídeo , Proteínas Recombinantes , Transplante Homólogo
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(4): 1196-200, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27531799

RESUMO

OBJECTIVE: To investigate the expression profile of lncRNA NONHSAT040475 in peripheral blood leukocytes of healthy persons. METHODS: The peripheral blood mononuclear cells were collected from 10 healthy volunteers, the CD3(+) T cells,CD19(+) B cells,CD56(+) NK cells and granulocytes were purified and sorted by flow cytometry. Then, the expression of lncRNA NONHSAT040475 in peripheral blood leukocyte subsets was detected by real-time quantitative PCR. RESULTS: the expression levels of lncRNA NONHSAT040475 were various in lymphocyte subsets, its expression in B lymphocytes was significantly higher, as compared with T lymphocytes, while the expressions of lncRNA NONHSAT040475 in NK cells and granulocytes were relative low(P<0.01). CONCLUSION: lncRNA NONHSAT040475 is widely expressed in human peripheral blood leukocytes, and mainly expressed in B lymphocytes, therefore, laying the foundation for further study of B lymphocyte-related diseases. This study has brought a new opportunity for diagnosing and illustrating the molecular mechanism of hematologic disorder or autoimmune disease.


Assuntos
Leucócitos , Citometria de Fluxo , Humanos , Células Matadoras Naturais , Contagem de Leucócitos , RNA Longo não Codificante
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 22(6): 1702-6, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25543500

RESUMO

The adhesion and polarization of T lymphocytes involved in the adhesive interaction of lymphocyte function-associated antigen 1 (LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulation in vitro on the adhesion and polarization of CD4⁺ T cells of healthy human in peripheral blood. The peripheral blood mononuclear cells were collected from 12 healthy volunteers. The CD4⁺ T cells were sorted by miniMACS. The sorted CD4⁺ T cells were incubated with rhG-CSF for 24 h, then the adhesion and polarization of CD4⁺ T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by ELISA and inverted microscope. The results showed that the percentage of adhesion CD4⁺T cells in the experimental group (rhG-CSF acting on the healthy adult volunteers) (61.9 ± 5.9)% was lower than that in the control group (healthy adult volunteers without rhG-CSF stimulation) (68.3 ± 7.3)% (P < 0.05). The percentage of polarized CD4⁺T cells in the experimental group (24.3 ± 4.3)% was also lower than that in control group (47.1 ± 5.1)% (P < 0.05). It is concluded that the adhesion and polarization of CD4⁺T lymphocytes can be inhibited after rhG-CSF stimulation.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Idoso , Adesão Celular/efeitos dos fármacos , Movimento Celular , Quimiocina CXCL12 , Humanos , Técnicas In Vitro , Molécula 1 de Adesão Intercelular , Leucócitos Mononucleares , Ativação Linfocitária , Antígeno-1 Associado à Função Linfocitária , Pessoa de Meia-Idade , Proteínas Recombinantes
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 22(2): 470-4, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24763025

RESUMO

The polarization and migration of T lymphocytes involves the adhesive interaction of lymphocyte function-associated antigen 1(LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilization on the polarization and migration of donor's CD4(+) T cells in peripheral blood. The peripheral blood mononuclear cells were collected from 10 healthy volunteers and 10 donors on the fifth day of mobilization with rhG-CSF. And the CD4(+)T cells were purified by miniMACS. The polarization and migration of CD4(+) T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by using inverted and confocal microscopes respectively. The results showed that the percentage of polarized CD4(+)T cells from donors(32.42 ± 4.91)% was lower than that from healthy controls(56.55 ± 5.35)% (P < 0.01), the migration velocity of CD4(+)T cells from donors (7.06 ± 1.44 µm/min) was also lower than that of healthy controls(9.05 ± 1.91 µm/min)(P < 0.01). It is concluded that the polarization and migration of CD4(+)T lymphocytes is impaired after rhG-CSF mobilization.


Assuntos
Linfócitos T CD4-Positivos/citologia , Movimento Celular , Fator Estimulador de Colônias de Granulócitos/farmacologia , Adolescente , Adulto , Linfócitos T CD4-Positivos/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia , Doadores de Tecidos , Adulto Jovem
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(2): 412-5, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22541110

RESUMO

Natural killer (NK) cells can suppress the development of graft vs host disease (GVHD) while retaining antitumor response in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Sphingosine-1-phosphate receptor 5 (S1PR5) can regulate NK cell migration and distribution in vivo by interacting with sphingosine-1-phosphate (S1P). This study was aimed to investigate S1PR5 expression change of NK cells in allo-HSCT and to explore the relationship between S1PR5 change and frequency of acute/chronic graft-versus-host disease (aGVHD/cGVHD). The S1PR5 expression was detected by real time quantitative PCR in the RNA extracted from blood NK cells of 17 couples of donor and recipient one month after allo-HSCT. The results showed that S1PR5 mRNA level variations in NK cells of donors and recipients post-allo-HSCT were not statistically significant (0.235 ± 0.191 vs 0.330 ± 0.261, P > 0.05). S1PR5 expression of NK cells was significantly lower in patients with aGVHD than those in patient without aGVHD (0.973 ± 0.834 vs 6.166 ± 5.32, P < 0.05). Compared with the corresponding donor, S1PR5 expression levels of patient declined by more than 10 that caused the high incidence of aGVHD. No significant correlation was found between S1PR5 expression of NK cells and cGVHD (3.401 ± 2.324 vs 2.762 ± 1.972, P > 0.05). It is concluded that the decreased expression level of NK cells S1PR5 is associated with aGVHD occurrence. Possible mechanism is due to S1PR5 low expression affecting distribution of NK cells in vivo, so affecting the regulation of NK cells for aGVHD.


Assuntos
Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células Matadoras Naturais/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Transplante Homólogo/efeitos adversos
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