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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1672-1677, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607330

RESUMO

OBJECTIVE: To investigate the clinical characteristics, prevention and treatment of invasive fungal disease (IFD). METHODS: The clinical data of 164 patients who met the diagnostic criteria of IFD in our center from January 2012 to January 2015 were retrospectively analyzed. The incidence, clinical characteristics, related factors, treatment methods and prognosis were analyzed. RESULTS: Among 1289 cases of blood diseases, 164 cases suffered from IFD with inciduce of 12.7%. The main infection sites were as followed: lung, blood and gastrointestinal tract, with incidence of 84.2%, 5.5% and 3% respectively. The funge was found in 35 cases by detection; among fungi, the detected rate of candida albicans. aspergillus and candida glabrata was more high with 51.5%, 20% and 14.3% respectively. Among 164 childen with blood deseases complicated by IFD, 36 cases gained complete remission, 97 cases gained partial remission, 10 cases were stable, 11 cases were progressive and 10 cases died, the overall effective rate reached 81.1%. The univariate analysis showed that the gramulopenia, granulocyte recovery, long-term use of corticosteroid and immuno-suppressive agents, as well as different grades of diagnosis were significant factors affecting the efficacy of antifungal therapy for blood disease children with IFD, the multivariate analysis further showed that the granulocyte recovery and diagnosis grades were independent prognostic factors affecting the therapeutic efficacy for IFD children. The overall survival rate of IFD children with 12 weeks of antifungal treatnment was 81.7%, out of which the survival rate of IFD children at 12 weeks of treatment with itraconazole, voriconazole, amphotericin B and caspofungin was 81.4%, 80%, 69.4% and 97.1% respectively, there were significant differences in survival rate between each other by long rank test. In addition of caspofungin, the other 3 kinds of drugs had toxic side effects of different degrees, but IFD children could tolerated these effects after symptomatic treatment. CONCLUSION: The incidence of IFD in children with blood deseases in our hospital is 12.7%, the lung is most common infective site, moreover patogens of IFD mainly is candida. The promotion of granulocyte recovery and early stratified diagnosis can contribule to the treatment of IFD. For the IFD children with better economic condition, the caspofungin is a potent antifungal agent with high efficacy, low toxicity and better prognosis.

2.
Hematology ; 24(1): 577-582, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31389303

RESUMO

Objective: To investigate clinical features, diagnosis, treatment strategies and prognosis of juvenile myelomonocytic leukemia (JMML). Methods: The clinical data of 21 patients with JMML who were diagnosed in our hospital from January 2013 to May 2018 were retrospectively analyzed. Results: Among the 21 children with JMML, 16 were male and 5 were female. Out of the 21 children who were diagnosed with JMML, 7 were lost after treatment while the remaining 14 received A-3V chemotherapy regimen of South Korea. The effective response rate was 78.5%. The three-year overall survival (OS) rate and three-year disease-free survival (DFS) rate were (76.2 ± 14.8)% and (66.2 ± 14)%, respectively. Single factor analysis showed that PLT count ≤33×109/L, LDH level >500 U/L and HbF level >10% and chemotherapy only were the significant factors that lead to poor prognosis in children. Cox multivariate analysis showed that the choice of treatment options affected the prognosis of JMML children. By taking prognostic factors for long-term efficacy into account, patients with treatment strategy of chemotherapy alongside hematopoietic stem cell transplantation (HSCT) have a better prognosis. Conclusion: The PLT count, LDH level, HbF level and choice of treatment plan are important for the evaluation of prognosis for children with JMML. Although there is a lack of consistency in terms of donors but the A-3V scheme is relatively stable, so HSCT should be preferred for children with poor prognostic factors.

3.
Clin Transplant ; 33(8): e13641, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31211850

RESUMO

OBJECTIVE: The purpose of our study was to evaluate the diagnostic value of serum galactomannan antigen (GM) testing combined with chest computed tomography (CT) of invasive pulmonary aspergillosis (IPA) in pediatric patients after hematopoietic stem cell transplantation. METHODS: A retrospective nested case-control study was conducted in the identifying IPA among pediatric patients. RESULTS: A total of 141 eligible pediatric recipients with febrile neutropenia were enrolled in this study. All patients in the cases were diagnosed with proven-probable IPA(PP-IPA), while only 9 patients in the controls. GM testing was positive in 38 pediatric recipients in the cases and nine recipients in the controls with sensitivity of 62.3%, specificity of 81.8%. Among all patients with IPA, 46 patients in the cases and 9 patients in the controls had typical features of CT imaging with sensitivity of 79.3%, specificity of 85.2%. For discrimination of participants' GM testing combined with CT evaluation, the AUC of the diagnostic model was 0.887 with PPV of 0.764, and NPV of 0.872. Sensitivity was 0.793, and specificity was 0.852 in IPA. CONCLUSION: The combination methods with serum GM and CT scan might be used as a valuable marker for early diagnosis of IPA in pediatric patients after HSCT.

4.
Acta Haematol ; 142(3): 162-170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091521

RESUMO

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

5.
Hemoglobin ; 43(1): 38-41, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30915867

RESUMO

To evaluate the iron metabolism and oxidative status in patients with Hb H disease, we investigated 43 patients with Hb H disease, including eight deletional Hb H disease patients and 35 nondeletional Hb H disease patients and 20 healthy controls. The levels of hematological parameters, serum ferritin, hepcidin, superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity (TAC), were examined. We found higher serum ferritin levels and lower hepcidin, MDA and TAC levels in Hb H disease patients than in controls. The hepcidin level in Hb H disease patients was positively correlated with MDA and TAC levels but not with serum ferritin and SOD levels. The patients with nondeletional Hb H disease showed higher serum ferritin and Hb H concentrations than those patients with deletional Hb H disease. However, no statistically significant differences in SOD, MDA and TAC levels were found in patients with deletional and nondeletional Hb H disease. Oxidative stress and antioxidant defense were related to hepcidin levels. Our study indicated that hepcidin might be an important parameter for monitoring the iron metabolism and oxidative status of Hb H disease patients.

6.
Transpl Infect Dis ; 21(3): e13066, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30859662

RESUMO

BACKGROUND: Invasive fungal disease (IFD) has a poor prognosis in children with hematological disorders after hematopoietic stem cell transplantation (HSCT). We assessed if drug combinations with different targets may improve the outcome. METHODS: Retrospective study to assess the outcome of combination antifungal therapy (CAT) for proven-probable IFD (PP-IFD) in children with hematological disorders after HSCT from January 2008 to June 2018. RESULTS: Over the 10-year period, 95 PP-IFD were diagnosed in pediatric recipients, median age of 5.6 years. Twenty-seven patients received combinations of caspofungin and voriconazole, 28 patients received combinations of caspofungin and amphotericin B, and 40 patients received combinations of voriconazole and amphotericin B. The overall response rate of PP-IFD was 77.9%, while the 100-day overall survival rates were 66.8%. Univariate analysis showed that factors that significantly affected the response to combination treatments were type of combination (P = 0.02), the stem cell source (P = 0.04), the donor type (P = 0.03), HLA-match (P = 0.03), aGVHD (P = 0.02), period of treatment (P = 0.044), use of corticosteroids (0.036), CD4:CD8 ratio (P = 0.014), and CMV viremia (P = 0.033). In addition, multivariate analysis demonstrated that only the type of combination remained a significant factor (odds ratio = 0.335, 95% confidence interval: 0.071-0.812, P = 0.042). Forty-three children suffered from mild and reversible adverse reactions, no serious side effects during treatment. CONCLUSION: A variety of factors can affect the outcome of CAT. Combination of caspofungin with voriconazole is a safe and helpful treatment option for HSCT recipients with IFD.


Assuntos
Antifúngicos/uso terapêutico , Doenças Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Fúngicas Invasivas/tratamento farmacológico , Micoses/tratamento farmacológico , Adolescente , Anfotericina B/uso terapêutico , Caspofungina/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Doenças Hematológicas/microbiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/microbiologia , Humanos , Lactente , Masculino , Micoses/etiologia , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Voriconazol/uso terapêutico
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(6): 1695-1701, 2018 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-30501706

RESUMO

OBJECTIVE: To analyze the clinical features and prognosis of 28 children with myelodysplastic syndrome (MDS) and to screen the high risk factors affecting the prognosis so as to provide the new ideas for standard of clinical diagnosis and therapy. METHODS: The clinical data of 28 children with newly diagnosed MDS treated in our hospital from March 1994 to July 2016 were analyzed retrospectively, the features of disease onset and the results of laboratory examination were summarized, all MDS children were followed up, the prognosis and the high risk factors affecting the prognosis were evaluated. RESULTS: In all 28 MDS children, the ratio of male to female was 1.8∶1, the incidence of MDS was observed in boys, while the low incidence of MDS was found in older children. The clinical manifestations were mainly the decrease of three series blood cells in 16 cases (57.14%), other cases presented simple anemia (7.1%), simple thrombocytopenia (7.1%), neutropenia with anemia (14.29%), and anemia with thrombocytopenia (14.28%).The bone marrow image showed mainly hyperplasia (82.14%), and the pathological hematopoiesis, moreover the manifistation of pathological hematopoiesis was different in forma and degree; the bone marrow biopsy showed the typical abnormal localization of immature precursor(ALIP) accepted for 33.33%; the chromosome karyotype detection showed the detected rate of chronosome abnormality was 41.18%. The median follow-up time was 1.75 years. 5 children with MDS received the hematopoietic stem cell transplantation (HSCT), among them 1 dead and 4 maintained CCR; Out of other 23 patients no-received HSCT, 7 cases given up treatment after confirmed diagnosis, 16 cases received the chemotherapy (2 cases given up treatment after CR, 5 cases transformed into AML, 3 cases relapsed, 3 cases maintained CCR), 11 cases dead, 9 cases failed to be followed up. The 5-years OS rate and EFS rate in all patients were predicted as (38.2±11.3)% and (35.3±11.3)%,respectively, among them, the OS and EFS rates of patients received the HSCT allo superior to those of patients did not received HSCT ï¼»(80.0±17.9)% vs.(22.8±11.5)%ï¼½ (P<0.05) and ï¼»(80.0±17.9)% vs (17.5±11.1)%ï¼½(P<0.05). Analysis showed that in addition to receiving the HSCT(P<0.05), platelet decrease in peripheral blood(P<0.01), the age, sex, existance of micromegakaryocytes in bone marrow and progressive MDS or no influenced not on the prognosis(P>0.05). CONCLUSION: The children MDS is rare and easy to be misdiagnosis, moreover displays more high heterogeneity and poor prognosis, thereby the early diagnosis is crucial, in addition, the system of prognosis evaluation is imperative to be perfected. The HSCT may be the effective method for curative treatment of childhood MDS.

8.
Clin Transplant ; : e13459, 2018 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-30506735

RESUMO

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is an increasingly recognized serious complication of Cyclosporine A (CSA) and tacrolimus (TAC) use in hematopoietic cell transplantation (HCT) recipients. PROCEDURE: A retrospective study was carried out, including 84 cases of HCT for TM from January 2012 to January 2017. 11 cases were diagnosed with PRES. RESULTS: The cumulative incidence of PRES was 13.4% (95%CI 9.7-17.2%). The median onset time of the symptoms was 63 [20, 143] days after transplantation. Lumber puncture found that CSF was normal. Univariate analysis showed that patients who received methylprednisolone (MP) (OR=10.629 95% CI, 1.360 to 83.071, p=0.024), female patients (OR=4.275, 95% CI, 1.154 to 15.843, p=0.032), patients who had severe hypertension (OR=5.162, 95% CI, 1.042 to 25.559, p=0.029) had significantly higher risks of PRES. Multivariate analysis showed that severe hypertension (hazard ratio [HR], 12.793; 95% CI, 1.477 to 110.813; P = 0.021), and Pesaro class 3 (HR, 3.367; 95% CI, 1.210 to 9.368; P = 0.020) were associated with PRES. CONCLUSIONS: The severe hypertension is an independent risk factor for PRES post-HCT in children with thalassemia major. Patients of Pesaro class 3 may benefit from optimum control of blood pressure post-HCT for prophylaxis of PRES. This article is protected by copyright. All rights reserved.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(4): 1167-1173, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30111425

RESUMO

OBJECTIVE: To prospectively study the correlation BKV with the occurrence and development of late onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT). METHODS: The clinical data of a total of 276 patients with allo-HSCT in our department between January 1998 and March 2016 were analyzed ratrospectvely. Quantitative Real-time PCR assay was used to prospectively monitor the BKV DNA load of the urine and plasma for 23 patients accepting allo-HSCT from August 2015 to March 2016. RESULTS: LOHC(24.28%) occurred in 67 of 276 cases with allo-HSCT. Univariate analysis showed that age older than 6 years, different diseases, unrelated donor, pretreatment with BU, Ⅲ-Ⅳ aGVHD significantly correlated with LOHC. Multivariate analysis demonstrated that age older than 6 years (P<0.01), pretreatment with BU(P<0.05), and aGVHD of grade Ⅲ-Ⅳ (P= 0.011) were the independent risk factors for LOHC. Among 23 patients after allo-HSTC, 10 of which were positive of urine BKV, and LOHC occurred in 6 cases. The positive rate of urine BKV (85.7%)in group LOHC+ was significantly higher than that in the group LOHC-(25.0%)(χ2=5.043, P<0.01). The incidence of LOHC positively correlated with the positive rate of BKV (r=0.564, P<0.01), and the severity of LOHC positively correlated with urinary BKV load (r = 0.502, P<0.01). And 5 of 6 petriatic patients with LOHC had aGVHD. All of them were subject to the strengthened antiviral treatment, and 4 of them accepted intensive immunosuppression therapy. CONCLUSION: Age ≥6 years old, precenditioning regieme with BU and aGVHD of grade Ⅲ-Ⅳ are independent risk factors for LOHC after allo-HSCT, the positive rate of urine BKV load positively correlates with the severity of LOHC after allo-HSCT.


Assuntos
Cistite , Criança , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemorragia , Humanos , Incidência , Fatores de Risco , Transplante Homólogo
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 900-904, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950240

RESUMO

OBJECTIVE: To study the curative effect and safety of menchymal stem cell infusion in treatment of children with refractory late-onset hemorrhagic cystitis(LOHC) after allogeneic HSCT. METHODS: Thirty cases of children with refractory LOHC after allo-HSCT in our department between December 2010 and July 2016 were analyzed retrospectively, out of 30 cases 7 received MSC treatment. The used MSC of all were four-to-five generation MSC from bone marrows of third party donors, and were infused into patients with (1.87±0.456)×106/kg MSCs once a week (1-4 times in total) until the hematuria and odynuria symptoms being improved. To observe whether unfavorable reactions occurred after MSC treatment, the patients accepted daily physical examination and regular assistant examination. The cytokine levels were also measured and dynamically detected in 2 cases before and after MSC treatment. RESULTS: In 30 children with refractory LOHC, the hematuria difficultly reached the remission after routine hydration, alkalizing and antiviral therapy, Among 25 cases who were received methylprednisolone, MTX and CTX therapy, 7 cases received MSC infusion for 1-4 times with dose of (1.87±0.456)×106/(kg·time) as a result, 7 cases of LOHC were cured. The TNF-α and IL-2R levels in 2 cases progressively decreased after MSC infusion, no occurence of fever, rash, embolism and so on were found in 7 cases received MSC infusion; the BKV detection showed that the viral load did not increase; the leukemia relapse or secondary cancer did not occure. CONCLUSION: The MSC treatment is safe and effective for refractory LOHC after allo-HSCT.


Assuntos
Cistite , Criança , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Mesenquimais , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(2): 375-381, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29665901

RESUMO

OBJECTIVE: To investigate the efficacy and safety of NOPHO-AML 2004 chemotherapy regimen for treatment of children with acute myelocytic leukemia(non-M3). METHODS: Thirty-three patients aged 1-13 with acute myelocytic leukemia (non-M3) were diagnosed from January 2013 to June 2017. FAB typing showed that 1 case in M0, 4 cases in M1, 12 cases in M2, 5 cases in M4, 8 cases in M5, 1 case in M6, and 2 cases in M7; Risk stratification showed that: 19 cases in standard risk, and 14 cases in high risk. All patients were treated with NOPHO-AML 2004 chemotherapy regimen. SPSS 22.0 software was used, the Kaplan-Meier survival analysis method and Cox regression model were used for statistical analysis. RESULTS: In the first course of treatment (AIET), among 33 child patients there were 27 cases with complete remission, and 5 cases with non-remission, thus the remission rate was 81.8%. Out of the 5 child patients without remission, 4 cases reached to the complete remission after the second course (AM), and 1 case did not remission, thus the total remission rate was 96.9%.9 cases (27.3%) underwent bone marrow recurrence and the median recurrence time was 30 months after complete continuous remission. Univariate analysis showed that age and erythrocyte transfusion frequency were significant factors to affect the early treatment response; the multiple Cox regression analysis showed that: age >7, MRD positive, erythrocyte transfusion >4 times and poor response to early treatment were independent risk factors for recurrence; Allogeneic hematopoietic stem cell transplantation(HSCT) in 8 high-risk children received enhanced chemotherapy had better efficacy as compared with the chemotherapy alone. The 3-year event-free survival rate was 59.9%, and 3-year overall survival rate was 69.2%. 33 children patients experienced varying degrees of infection and myelosuppression, or drug-related gastrointestinal reactions and allergic reactions, patients were tolerable to these side reactions after active symptomatic treatment. CONCLUSION: NOPHO-AML 2004 chemotherapy regimen has high response rate and good tolerance, early treatment response is an important factor influencing prognosis. Age and repeated red blood cell infusions are the important factors influencing the prognosis, which promote bone marrow recurrence in AML children. For the children suffered from clinical high-risk AML, the NOPHO-AML 2004 chemotherapy regimen combined with HSCT can improve the prognosis of patients.


Assuntos
Leucemia Mieloide Aguda , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Prognóstico , Indução de Remissão , Resultado do Tratamento
12.
J Pediatr Hematol Oncol ; 40(6): 472-477, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29608548

RESUMO

OBJECTIVE: To explore the clinical features and outcomes of relapsed childhood acute lymphoblastic leukemia (ALL) at our center, achieve the early detection of risk factors for recurrence and assess the risk-stratified Guangdong (GD)-2008 ALL protocol. MATERIALS AND METHODS: In total, 59 Chinese childhood ALL patients treated with the GD-2008 ALL protocol who relapsed between July 2008 and March 2015 were enrolled in this study. Their clinical features and outcomes were retrospectively analyzed and compared with those of 218 patients who achieved continuous complete remission. RESULTS: Of the 285 study participants, 8 died of treatment-related infections or other complications before remission, 218 achieved continuous complete remission, and 59 patients relapsed, yielding a relapse rate of 20.7%. The number of relapsed patients in the standard-risk, intermediate-risk, and high-risk groups were 15 (17.0%), 27 (19.7%), and 17 (32.7%), respectively. Risk factors included age 10 years and above at first diagnosis, white blood cell (WBC) count ≥50×10/L, poor prednisone response, failure to achieve bone marrow complete remission at day 15 of induction chemotherapy. High-risk stratification and a high level (≥0.1%) of minimal residual disease at day 33 were the risk factors for relapse. Multivariate analysis showed that a high WBC at first diagnosis was an independent risk factor for relapse (P=0.000). CONCLUSION: For the GD-2008 ALL risk stratification based on age and initial WBC, 10 years of age and WBC 50×10/L can be used as cut-offs. Patients at high risk benefited from the GD-2008 ALL protocol. In addition, the impact of minimal residual disease on prognosis should be considered.

13.
World J Pediatr ; 14(1): 92-99, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29511925

RESUMO

BACKGROUND: ß-Thalassemia major (ß-TM) has become a public health problem in mainland China. Hematopoietic stem cell transplantation (HSCT) has remained the only cure for ß-TM in mainland China since 1998. METHODS: This multicenter retrospective study provides a comprehensive review of the outcomes of 50 pediatric patients with ß-TM who received HSCT between 1998 and 2009 at five centers in mainland China. Both related (n = 35) and unrelated donors (n = 15) with complete human leukocyte antigen matches were included. The stem cell sources included bone marrow (BM), peripheral blood stem cells, umbilical cord blood (UCB) and a combination of BM and UCB or a combination of BM and peripheral blood stem cells from a single sibling donor. RESULTS: The probabilities of 5-year overall survival (OS) and thalassemia-free survival (TFS) after the first HSCT were 83.1 and 67.3%, respectively. Graft failure (GF) occurred in 17 patients. Univariate analyses showed that umbilical cord blood transplantation (UCBT) was one of the potential risk factors for decreased OS (P = 0.051), and that UCBT (P = 0.002) was potentially related to TFS. GF incidence was distinct between the UCBT and non-UCBT groups (P = 0.004). Four cases of UCB-BM combined transplantation led to decreased risks of mortality and recurrence. In the UCBT group, related donor transplantation produced more favorable results than unrelated donor transplantation in OS (P = 0.009) but not in TFS (P = 0.217). CONCLUSIONS: GF was the primary cause of UCBT failure. Though UCBT from related donors was not favorable, the combined transplantation of UCB and BM could improve the prognosis of UCBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Talassemia beta/cirurgia , Adolescente , Análise de Variância , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Intervalos de Confiança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Talassemia beta/diagnóstico , Talassemia beta/mortalidade
14.
Pediatr Blood Cancer ; 65(7): e27026, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29512932

RESUMO

BACKGROUND: The objective of this study was to evaluate the feasibility of a modified conditioning regimen for the treatment of patients with ß-thalassaemia major (TM), using unrelated donor peripheral blood stem cell transplantation (UD-PBSCT). METHODS: A modified conditioning regimen based on intravenous busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin was performed in 50 consecutive childhood patients with ß-TM and a median age of 4.6 years (range, 2-12 years). According to Pesaro's classification, three classes of risk are identified using the criteria of degree of hepatomegaly, portal fibrosis, and quality of the chelation treatment. Patients with three adverse criteria constituted class III, none of the adverse criteria constituted class I, and one or two of the adverse criteria formed class II. Ten patients were class I, 36 class II, and four class III. All patients were transplanted with UDs containing 37 of 10/10 human leukocyte antigen (HLA)-matched pairs, 11 of 9/10 matched pairs, and two of 8/10 matched pairs. The median follow-up was 36 months (range, 9-96 months). RESULTS: All patients successfully achieved engraftment, two of whom developed persistent thrombocytopaenia. The incidence of acute graft-versus-host disease (aGVHD) grade III-IV and chronic graft-versus-host disease (cGVHD) were 12% and 8%, respectively. However, 8.3% of HLA-matched and 15.4% of HLA-mismatched patients developed aGVHD. The incidence of severe bacterial infections and fungal pneumonia was 12% and 20%, respectively. The 3-year overall survival, disease-free survival, graft rejection, and transplant-related mortality were 94%, 92%, 2%, and 6%, respectively. CONCLUSION: This modified conditioning protocol effectively improved outcomes of UD-PBSCT for patients with ß-TM.

15.
Exp Ther Med ; 14(3): 1884-1891, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28962099

RESUMO

Cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig) and anti-cluster of differentiation 154 (anti-CD154) are able to block B7/CD28 and CD40/CD154 co-stimulatory signals in T cells. Additionally, they promote hematopoietic stem cell transplantation (HSCT) in sensitized recipients and are able to induce immune tolerance and complete hematopoietic reconstitution. Indoleamine 2, 3-dioxygenase (IDO) and nitric oxide (NO) have been implicated in T cell immune tolerance. The aim of the present report was to study the in vivo tolerogenic mechanisms by which CTLA4Ig and anti-CD154 induce transplantation survival in mice receiving HSCT. BALB/c mice were sensitized via splenocyte transfusion and pretreated with CTLA4Ig plus anti-CD154 on day-7. IDO and inducible nitric oxide synthase (iNOS) inhibitors were applied on days-7 to 0 and the mice were divided into 4 groups (n=10) and injected with IDO every other day. The mice were sacrificed on day 0, and splenocytes were separated to identify CD11c+ antigen-presenting cells, which were subsequently assessed for IDO expression and activity. The concentration of NO was tested using a nitrate reductase kit. Following the acceptance of allogeneic HSCT, mice were tested for homing and engraftment, as well as survival rate. Application of the IDO inhibitor increased the concentration of NO, whereas a decrease in NO resulted in increased IDO activity. Immune tolerance was abrogated in the presence of both IDO and iNOS inhibitors, whereas this effect was not observed with either compound alone. CTLA4Ig and anti-CD154 may induce immune tolerance by affecting the activity of IDO and iNOS. This tolerance was abrogated in the presence of both IDO and iNOS inhibitors. A cross-regulatory pathway was observed between the IDO and NO pathways, in which the inhibition of IDO stimulated the iNOS pathway and vice versa.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(3): 936-940, 2017 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28641663

RESUMO

OBJECTIVE: To investigate the changes of hepcidin and ferropotin 1 expression in murine model of iron overload. METHODS: The murine model of iron overload was established, C57BL/6 mice were injected with iron dextran intraperitoneally (10 mg) every 3 days for 4 weeks. Blood routine, serum ferritin and pathological sections were tested at the appointed time-point respectively (before iron injection, 2 weeks and 4 weeks after treatment of iron injection). The serum hepcidin was assayed by enzyme-linked immunosorbent method. The expression of ferroportin 1 in bone marrow cells was detected by RT-PCR and Western blot, respectively. The labile iron pool of bone marrow cells was measured by flow cytometry. RESULTS: The absolute number and percentage of reticulocytes in the iron-overloaded mice were significantly decreased along with the increase of iron injection times (r=-0.938, r=-0.947), while no significant change was found in the number of white blood cells, hemoglobin level and platelet count. The level of serum ferritin was increased along with increase of iron injection time (r=0.894). Iron overload was found in pathological sections of different organs. Furthermore, serum hepcidin was increased along with increase of iron injection time (r=0.957). RT-PCR and Western blot analyses showed that the expressions of ferroportin 1 at mRNA and protein level were increased in the murine model of iron overload (P<0.05). Labile iron pool in bone marrow cells was also found to be increased in the murine model of iron overload(P<0.05). CONCLUSION: The expressions of hepcidin and ferroportin 1 are increase in a murine model of iron overload, which may be contributed to the suppression effect on erythropoiesis in bone marrow.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Hepcidinas/metabolismo , Sobrecarga de Ferro/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL
17.
Mol Med Rep ; 15(6): 3591-3598, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28440403

RESUMO

Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive components in Panax ginseng. The present study aimed to investigate the underlying mechanisms of apoptotic cell­death induced by GRh2 and GRg3 in human leukemia Jurkat cells. The Cell Counting kit­8 assay was used to determine cell proliferation. Apoptosis was detected by nuclear morphologic observation by Hoechst 33342 staining and Annexin V-allophycocyanin and 7-amino-actinomycin D assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was used to examine the effects of mitochondrial ROS on cell viability and mitochondrial membrane potential (MMP). Finally, the expression levels of numerous mitochondrial­associated apoptosis proteins were assessed by western blot analysis. These results demonstrated that GRh2 and GRg3 inhibited cell growth and induced apoptosis, and that GRh2 had greater cytotoxicity than GRg3. GRh2 induced generation of more mitochondrial ROS compared with GRg3 in Jurkat cells; however, this effect was ameliorated by subsequent treatment with mitoTEMPO. Furthermore, excess mitochondrial ROS induced by GRh2 was more potent than GRg3 in inhibiting cell proliferation and reducing MMP. In addition, expression levels of apoptosis­associated proteins were significantly increased in Jurkat cells treated with GRh2 than GRg3. In conclusion, these findings suggested that GRh2 and GRg3 induce mitochondrial-associated apoptosis by increasing mitochondrial ROS in human leukemia Jurkat cells. GRh2 may more effectively inhibit cell growth and accelerate apoptosis than GRg3. This study provides a potential novel strategy for the treatment of acute lymphoblastic leukemia.


Assuntos
Apoptose/efeitos dos fármacos , Ginsenosídeos/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica , Humanos , Células Jurkat , Metaloproteinases da Matriz/metabolismo
18.
J Trop Pediatr ; 63(5): 389-394, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28158572

RESUMO

Background: This study evaluated the efficiency of corticosteroid, leflunomide and mesenchymal stem cells (MSCs) in the treatment of pediatric idiopathic pulmonary hemosiderosis (IPH). Methods: Ten patients were included in the study. The diagnosis of IPH was based on clinical symptoms, laboratory examinations and pulmonary hemosiderosis. Induction therapy consisted of methylprednisolone pulse therapy, followed by prednisone plus leflunomide. Maintenance therapy consisted of low-dose prednisone, leflunomide and administration of MSCs. Results: All the patients achieved complete response after treatment with corticosteroid, leflunomide and MSCs. The median follow-up was 23 months (range: 4-34 months). Moreover, administration of MSCs induced an increase in the percentage of CD4+ CD25+ regulatory T cells but a decrease in the percentage of Th17 cells. Conclusion: Treatment with corticosteroid, leflunomide and MSCs for pediatric IPH was safe and effective.


Assuntos
Corticosteroides/uso terapêutico , Hemossiderose/terapia , Imunossupressores/uso terapêutico , Isoxazóis/uso terapêutico , Pneumopatias/tratamento farmacológico , Transplante de Células-Tronco Mesenquimais , Criança , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hemossiderose/diagnóstico , Humanos , Leflunomida , Pneumopatias/diagnóstico , Pneumopatias/terapia , Masculino , Células-Tronco Mesenquimais , Metilprednisolona/uso terapêutico , Prednisona/administração & dosagem , Pulsoterapia , Estudos Retrospectivos , Resultado do Tratamento
19.
Pediatr Hematol Oncol ; 34(8): 428-434, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29303623

RESUMO

X-linked hyper-immunoglobulin M (IgM) syndrome is characterized by recurrent infections, low or undetectable levels of IgG and IgA, and normal to increased serum IgM, and is also rare. It is associated with mutation in the gene encoding CD40 ligand. This study aimed to describe the first international report of hemizygous CD40LG c.542G>A mutation in a 5-year-old boy with a phenotype of Crohn's disease and hemophagocytic lymphohistiocytosis. Also, the clinical implications of this mutation and associated atypical phenotype are discussed.


Assuntos
Ligante de CD40/genética , Doença de Crohn , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1 , Linfo-Histiocitose Hemofagocítica , Fenótipo , Mutação Puntual , Pré-Escolar , Doença de Crohn/sangue , Doença de Crohn/genética , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/sangue , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/genética , Masculino
20.
J Hematol Oncol ; 9: 12, 2016 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-26892465

RESUMO

BACKGROUND: Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR) inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK) down-regulation in the treatment of ALL. METHODS: The effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model. RESULTS: When combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 cell cycle arrest, and apoptosis were significantly enhanced. In addition, REH cell-injected NOD/SCID mice treated with rapamycin and a short-hairpin RNA (shRNA) to down-regulate FAK had significantly longer survival times and slower leukemia progression compared with mice injected with REH-empty vector cells and treated with rapamycin. Moreover, the B-cell CLL/lymphoma-2 (BCL-2) gene family was shown to be involved in the enhancement, by combined treatment, of REH cell apoptosis. CONCLUSIONS: FAK down-regulation enhanced the in vitro and in vivo inhibitory effects of rapamycin on REH cell growth, indicating that the simultaneous targeting of mTOR- and FAK-related pathways might offer a novel and powerful strategy for treating ALL.


Assuntos
Quinase 1 de Adesão Focal/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Interferência de RNA , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adolescente , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Criança , Pré-Escolar , Terapia Combinada , Regulação para Baixo/genética , Feminino , Quinase 1 de Adesão Focal/metabolismo , Humanos , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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