Institute of Hematology and Blood Diseases Hospital

Tianjin, China

Institute of Hematology and Blood Diseases Hospital

Tianjin, China
SEARCH FILTERS
Time filter
Source Type

Wan Y.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2016

OBJECTIVE: To summary clinical and genetic features of childhood dyskeratosis congenital (DC) patients with bone marrow failure.METHODS: The clinical data of 8 DC patients with bone marrow failure diagnosed between September 2010 and September 2015 were collected. Whole exons with flanking regions of the 16 telomere-related genes, including DKC1, TERC, TERT, NOP10, NHP2, TINF2 and so on, were analyzed by next generation sequence.RESULTS: Six males and two females were included, with a median age of 42(15-60) months. The median blood cell count at onset were as follow: WBC 3.99 (1.26-5.44) × 10(9)/L, ANC 1.11 (0.38-2.15) × 10(9)/L, RBC 2.45 (0.37-3.56) × 10(12)/L, HGB 82.5(15-127) g/L, PLT 27 (2-112) ×10(9)/L. Hypoplastic or marked hypoplastic bone marrow were seen in 6 patients. DKC1 mutiaton were indentified in 3 patients: one c.961C>A mutation, and two c.1058C>T mutation. TINF2 mutations were identified in 4 patients: c.849delC, c.844C>T, c.811C>T, c.862T>A combined c.871delA. One patient had TINF2 mutation c.848C>A combined TERT mutation c.1138C>T. DKC1 c.961C>A mutation, TINF2 c.849delC mutation and TINF2 c.871delA mutaion were not reported so far. 5 of 7 patients got better after androgen administration. During follow-up, one patient died of serious infection, the other seven patients continued the treatment.CONCLUSIONS: TINF2 and DKC1 mutations were the main genetic phenotypes in childhood DC with marrow failure patients. Androgen is effetive in some cases.


Yang W.R.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2016

OBJECTIVE: To analyze the clinical characteristics and to evaluate immunosuppressive therapy (IST) response and survival in hepatitis-associated aplastic anemia (HAAA).METHODS: We retrospectively analyzed clinical characteristics, IST response, long-term survival and clonal evolution in 41 HAAA patients, and compared those with age and bone marrow failure matched idiopathic aplastic anemia (IAA) patients.RESULTS: The prevalence of HAAA among cases of SAA was 4.34% (41/944). The proportion of VSAA in HAAA cases was significantly higher than IAA (65.9% vs 39.4%, P=0.001). There was no significant difference in the prevalence of hemorrhage and infections between HAAA and IAA patients, but the duration of infection persistence in HAAA group was much longer than IAA group [21 (4-100) d vs 13 (3-139) d, P=0.048]. The absolute counts of CD3(+) T-cell, CD3(+)CD4(+)T-cell, CD3(+)CD8(+)T-cell and ratio of CD4(+) T-cell/CD8(+) T-cell in HAAA were significant lower than that in IAA patients. However, the percentage of CD3(+)CD8(+)T-cell in HAAA was significant higher than that in IAA (P <0.05). The total response in HAAA and IAA patients treated with IST were 34.1% vs 34.1% (P=1.000), 56.1% vs 53.7% (P=0.787), and 73.2% vs 68.3% (P=0.558) at 3, 6, 12 months after IST, respectively. There were no significant difference in 5-year overall survival and event-free survival between HAAA and IAA patients (90% vs 87.1%, P=0.700; 71.9% vs 62.4%, P=0.450).CONCLUSION: HAAA was a rare distinct variant of aplastic anemia with more severe bone marrow failure and more severe imbalance of the T cell immune system than IAA. Treatment outcomes were comparable in patients with HAAA and IAA.


Li J.P.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2016

OBJECTIVE: To evaluate the efficacy and safety of intensive immunosupressive therapy (IST) with antithymocyte/antilymphocyte globulin plus cyclosporine A in the treatment of older patients (≥60 years) with severe aplastic anemia (SAA).METHODS: The hematologic response and safety of sixteen older SAA patients treated with IST regimen in our hospital were retrospectively analyzed , and the factors affecting response were also explored.RESULTS: A total of 16 older SAA patients were involved, the median age was 63.5 (60-79) years. Among them, 7 were VSAA and 9 were SAA; 9 patients received Rabbit anti- human thymocyte globulin (rATG), and 7 patients porcine anti- human lymphocyte globulin (pALG). Two patients died within 3 months after IST; at the 6 months after IST, 9 patients achieved hematology response and 5 patients had no response; overall response rate was 56.3%. Two (22%) of the 9 patients treated with rATG achieved hematology response; However, all 7 patients (100.0%) treated with pALG achieved hematology response. rATG/pALG associated adverse reactions were mild and easily managed.CONCLUSION: The older patients with SAA could still benefit from IST consisting of standard dose rATG/pALG with CsA, and the patients with VSAA had worse prognosis, pALG was inferior to rATG as a first treatment for SAA.


Xu Z.F.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2016

OBJECTIVE: To evaluate the prognostic value of JAK2, MPL and CALR mutations in Chinese patients with primary myelofibrosis (PMF).METHODS: Four hundred and two Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, the Log-rank test, the likelihood ratio test and the Cox proportional hazards regression model were used to evaluate the prognostic scoring system.RESULTS: This cohort of patients included 209 males and 193 females with a median age of 55 years (range: 15- 89). JAK2V617F mutations were detected in 189 subjects (47.0% ), MPLW515 mutations in 13 (3.2%) and CALR mutations in 81 (20.1%) [There were 30 (37.0%) type-1, 48 (59.3%) type-2 and 3 (3.7%) less common CALR mutations], respectively. 119 subjects (29.6%) had no detectable mutation in JAK2, MPL or CALR. Univariate analysis indicated that patients with CALR type-2 mutations or no detectable mutations had inferior survival compared to those with JAK2, MPL or CALR type- 1 or other less common CALR mutations (the median survival was 74vs 168 months, respectively [HR 2.990 (95% CI 1.935-4.619),P<0.001]. Therefore, patients were categorized into the high-risk with CALR type- 2 mutations or no detectable driver mutations and the low- risk without aforementioned mutations status. The DIPSS-Chinese molecular prognostic model was proposed by adopting mutation categories and DIPSS-Chinese risk group. The median survival of patients classified in low risk (132 subjects, 32.8% ), intermediate- 1 risk (143 subjects, 35.6%), intermediate- 2 risk (106 subjects, 26.4%) and high risk (21 subjects, 5.2%) were not reached, 156 (95% CI 117- 194), 60 (95% CI 28- 91) and 22 (95% CI 10- 33) months, respectively, and there was a statistically significant difference in overall survival among the four risk groups (P<0.001). There was significantly higher predictive power for survival according to the DIPSS-Chinese molecular prognostic model compared with the DIPSS-Chinese model (P=0.005, -2 log-likelihood ratios of 855.6 and 869.7, respectively).CONCLUSION: The impact of the CALR type- 2 mutations or no detectable driver mutation on survival was independent of current prognostic scoring systems. The DIPSS- Chinese molecular prognostic model based on the molecular features of Chinese patients was proposed and worked well for prognostic indication.


Yang W.R.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2013

To evaluate the value of serum soluble transferrin receptor (sTfR) concentration in predicting early response to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). Clinical data and hematologic responses of 140 SAA patients treated with rabbit antithymocyte globulin (rATG) combination with cyclosporine in our hospital were retrospectively analyzed. Correlation of pre-IST baseline of sTfR and IST responses was statistically analyzed and receiver operating characteristic (ROC) curve was used to estimate the sensitivity and specificity of sTfR in prediction of early responses. Serum concentration of sTfR in very SAA (VSAA) patients were significantly lower than SAA and transfusion dependent non-SAA cases (P=0.001). The responders, especially at 3 months, had significantly higher pre- IST baseline of sTfR [median, 0.89 (range, 0.21-2.42) mg/L] than that [median, 0.58 (range, 0.13-1.88) mg/L] of non-responders (P=0.005). The cutoff level of 0.91 mg/L and 0.88 mg/L for predicting responses at 3 and 6 months were established based on the ROC curve, with the degree of accuracy of 65.0% and 60.7% respectively. Multivariate analysis showed that pre-IST baseline of sTfR was the independent factor of predicting response at 3 months (P=0.007) and at 6 months (P=0.021). As a indicator of bone marrow failure severity, sTfR could predict early response to IST therapy in aplastic anemia.


Wang C.C.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2012

To investigate the expression of PTEN (phosphatase and tension homology deletion on chromosome 10, PTEN) and its pseudogene PTENP1 in acute leukemia (AL) and correlation between them, and to explore the role of PTENP1 on the PTEN expression in AL cells. PTEN and PTENP1 mRNA expression were evaluated in bone marrow (BM) samples from 138 newly diagnosed AL patients and 15 healthy controls by quantitative real-time RT-PCR (qRT-PCR). pCDH1-PTENP1 3'UTR-GFP lentivirus vectors were constructed. 293T cells were transfected by calcium phosphate precipitation to produce retrovirus. HL-60 cell line was infected with the retroviral vectors expressing pCDH1-GFP and pCDH1-PTENP1 3'UTR-GFP respectively. The flow cell sorter was used to sort the HL-60 with GFP positively expressed. The mRNA expression of PTEN and PTENP1 was detected by qRT-PCR, the expression of PTEN protein by western blot, and the impact of PTENP13'UTR on the proliferation of HL-60 cells by MTT assay. AML patients showed significantly lower PTEN and PTENP1 mRNA expression in BM compared to healthy controls. Correlation analysis showed that the expression of PTEN and PTENP1 mRNA were positively correlated (P < 0.05). The 108 cases of PTENP1(+) AML were classified according to the prognostic classification of 2011 NCCN Clinical Practice Guidelines in AML, there was no difference among different subgroups. HL-60 cell line was infected with the retroviral vectors expressing pCDH1-GFP (control group) and pCDH1-PTENP1 3'UTR-GFP respectively. Compared with the control group, PTENP1 mRNA level of HL-60 infected with the retroviral vectors expressing pCDH1-PTENP1 3'UTR-GFP increased significantly, and PTEN mRNA level also increased. While the PTEN protein level and the cell growth rate of the PTENP1 3'UTR group didn't change significantly. PTEN and PTENP1 mRNA expression level of BM cells from AL patients is significantly lower. There is a positive correlation between expression of PTEN and PTENP1 mRNA. PTENP1 may regulate the expression of PTEN in mRNA level.


Yang L.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2011

To investigate the relationship between DNA homologous recombination (HR) repair genes RAD51-G135C/XRCC3-C241T polymorphisms and development of acute myeloid leukemia (AML) with recurrent chromosome translocation. Genomic DNA was extracted from bone marrow cells of 625 de novo AML patients and peripheral blood cells of 806 patient family members and 704 unrelated volunteers. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by PCR-RFLP. Cell lines with genotypes differed from XRCC3-C241T were selected and irradiated in vitro. The CBFβ-MYH11 fusion gene was detected by TaqMan real-time PCR. The XRCC3-C241T variant (C/T + T/T) showed 6.22-fold and 6.99-fold increase in the risk of developing the AML with inv(16)/t(16;16)/CBFβ-MYH11 as compared with the volunteer and family member controls respectively; the RAD51-G135C homozygote-type (C/C) variant showed 0.87-fold (P = 0.010) and 1.15-fold (P = 0.001) respectively increase in the risk of this subtype AML. In the irradiated group, the CBFβ-MYH11 mRNA level in HL-60 cells was 59.49 times increased than that in KG1a cells. However, the RAD51-G135C and XRCC3-C241T variants had no correlations with the risk of development of t(15;17)/PML-RARα(+)AML, t(8;21)/AML1-ETO(+) AML and 11q23 AML subtypes. The XRCC3-C241T variant and the RAD51-G135C homozygote-type significantly increase the risk of the development of AML with inv(16)/t(16;16)/CBFβ-MYH11.


Wang J.Y.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2012

To investigate JAK2 exon 12 mutations in patients with Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPN) and the clinical characteristics of patients with JAK2 exon 12 mutants. Allele-specific PCR (AS-PCR) was applied to identify JAK2 V617F mutation. Genomic DNA corresponding to exon 12 of JAK2 gene and epigenetic regulator gene (TET2, ASXL1, EZH2) were amplified by polymerase chain reaction (PCR). Identification of mutants was by direct sequencing and classification of mutation types by sequencing followed by plasmid cloning. SNP genotyping of two 46/1 tag SNPs, rs12340895 and rs10974944, was analyzed using commercially available Taqman assays on the 7500HT real-time PCR instrument according to standard protocols. No JAK2 exon 12 mutation was detected in patients with ET, PMF or JAK2 V617F positive PV. Among 13 JAK2 V617F negative PV patients, JAK2 exon 12 mutation was detected as N542-E543del in 2(15.4%) patients who presented with a phenotype of predominant erythrocytosis and erythroid colonic grown from their bone marrow samples in the absence of exogenous EPO, reduced serum erythropoietin (EPO) level, and no mutations in TET2, ASXL1 or EZH2 genes. One of the affected patients was heterozygous for 46/1 but the second was negative for this haplotype. There was no need to detect JAK2 exon 12 mutation in ET, PMF or MPN-U patients without JAK2 V67F mutation. Ph negative MPN patients with JAK2 exon 12 mutations had somewhat unique clinical and laboratory features.


Liang C.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2013

To investigate mesenchymal stem cells (MSCs) immunosuppressive activity in the presence of interferon-gamma (IFN-γ) to reveal synergistic immunomodulatory effects of IFN-γ and MSCs. MSCs were cultured in the presence or absence of IFN-γ100 ng/ml, the supernatants were collected for measurements of PGE2HGF and TGF-β1 by ELISA kits. MSCs were cultured in the presence or absence of IFN-γ 100 ng/mlfor 48 h. The cDNA was analysed for the expression of human indoleamine 2, 3-dioxygenaseIDOmRNA by semiquantitative RT-PCR. Mononuclear cells (MNCs) were extracted from peripheral blood of healthy donors. The T cell proliferation was tested in the co-culture system added with MSCs, recombinant human IFN-γ (100 ng/ml) and anti-IFN-γ mAb (5 μg/ml) by BrdU ELISA kit. The immunosuppressive cytokines PGE2HGF and TGF-β1 were detectable within 24-48 h in the supernatants. Their expressions were significantly up-regulated in the presence of IFN-γ. Concentrations of these cytokines were as of (1715.5±628.6) pg/ml vs (1344.5±709.4) pg/ml (P=0.001);(4031.8±1496.8) pg/ml vs (2452.4±1375.3) pg/mlP=0.011;(1753.5±413.8) pg/ml vs (1026.6±450.5) pg/mlP<0.001,respectively. The expression of IDO mRNA was undetectable when MSCs were cultured alone. In contrast, The IDO mRNA expression was remarkably enhanced in the presence of IFN-γ. Bone marrow-derived MSCs remarkably suppressed allogeneic T cell proliferation in vitro. Addition of exogenous IFN-γ had no significant effect on the inhibitory capacity of MSCs, the inhibitory ratios of T cell proliferation were 40.4±10.9% vs36.7±7.4% (P=0.272). By contrast, the inhibitory ratio of T cell proliferation was significantly decreased in the presence of anti-IFN-γ mAb[(40.4±10.9)% vs (23.9±7.6)%,P=0.002]. Human MSCs constitutively expressed immunosuppressive concentrations of PGE2, HGF and TGF-β1, and their expressions were significantly up-regulated by IFN-γ. IFN-γ-induced expression of IDO on MSCs involved in tryptophan catabolism. MSCs notably suppressed allogeneic T cell proliferation in vitro. IFN-γ promoted the immunosuppressive capacity of human MSCs, indicating the synergistic immunomodulatory effect of IFN-γ and MSCs.


Yuan Y.,Institute of Hematology and Blood Diseases Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2011

To assess complete remission (CR), the overall survival (OS), event-free survival (EFS) and adverse events of newly diagnosed acute promyelocytic leukemia (APL) with homoharringtonine (HHT) plus ATRA, to evaluate the therapeutic effect by comparing HHT plus ATRA with daunorubicin plus ATRA as induction regimen (HA with DA as post-remission regimen). 115 APL patients (54 in HHT group, 61 in DNR group) after long-term follow-up were enrolled in the analyses of clinical feature, chromosome karyotype, molecular biology, OS and EFS. The overall CR of 115 patients was 100%, the median interval to achieve hematological CR was 32 (22 - 43) days, the overall median OS was within 0.23 - 77.34 months, median EFS was within 0.23 - 77.34 months. 3-year OS rate was 93%, 5-year OS rate 93%, 3-year EFS rate 85% and 5-year RFS rate 75% respectively. Converting to PML-RARα PCR-negative after the induction therapy in the HHT and DNR group was 31.3% and 15.5% respectively, at the end of 1 consolidation course was 68.6% and 77.6% respectively, while the remaining 4 patients tested PML-RARα PCR-negative at the end of 2 consolidation courses in the DNR group. While both groups obtained the identical molecular biology relapse rate (9.8% and 8.6%, respectively). Survival analysis indicated that no significant difference was found on OS and EFS between the HHT group and the DNR group (P = 0.206 and 0.506). 5-year OS rate was 87% for the HHT group while 98% for the DNR group, 5-years EFS rate was 80% for the HHT group while 71% for the DNR group. And the risk group was not the factor affecting OS and EFS (P = 0.615 and 0.416). Grade 2 fever in the HHT group was less than in the DNR group during induction therapy. And no difference was found in terms of liver dysfunction, renal dysfunction, cardiac dysfunction, and hematologic toxicity between two groups. Our study demonstrated comparable therapeutic effect of HHT or DNR on APL. HHT was also well tolerated and didn't cause serious adverse events.

Loading Institute of Hematology and Blood Diseases Hospital collaborators
Loading Institute of Hematology and Blood Diseases Hospital collaborators