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  • 21
    Online Resource
    Online Resource
    Who is the best donor for a related HLA haplotype-mismatched transplant?
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 6 ( 2014-08-07), p. 843-850
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 6 ( 2014-08-07), p. 843-850
    Abstract: There is a need to identify the best HLA haplotype-mismatched related donor. Use of young, male, NIMA-mismatched donors results in the best survival after HLA haplotype-mismatched related donor transplants.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2014-03-563130
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 22
    Online Resource
    Online Resource
    Risk-Stratification Directed Prophylaxis with Additional Low-Dose of Methylprednisolone Can Reduce Acute Graft-Versus-Host Disease for Patients with Hematological Malignancies after Allogeneic SCT: A Randomized, Controlled, Clinical Trial
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 40-40
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 40-40
    Abstract: The major complication of allogeneic HSCT-graft-versus-host disease (GVHD)-remains lethal and limits use of this important procedure, especially after unmanipulated haploidentical HSCT. Several studies have provided evidence that universal addition of corticosteroids for prophylaxis of GVHD can reduce the risk for acute GvHD grade II-IV in HLA-matched transplantation. However, corticosteroid, a non-specific immunosuppressive agent, may also contribute to high rates of infections. Our previous data suggest that the ratio of CD4/CD8 in allografts from haploidentical donors can stratify patients into high-risk and low-risk ones who will develop GVHD after transplantation. Recently, we indicated that low-dose of methylprednisolone (MP, 0.5 mg/kg/day) might be a well-tolerated, effective and inexpensive regimen in combination of MTX for therapy of GVHD, suggesting that low-dose corticosteroid may be used for the prophylaxis of GVHD without increasing infection. To investigate whether risk-stratification directed prophylaxis strategy can reduce the incidence of GVHD and improve survival in a hemogenous patient population who underwent unmanipulated haploidentical HSCT, we performed a prospective, randomized, controlled, clinical trial. A total of 228 patients were enrolled in this trial. All of the patients completed the study and were stratified as high-risk (n=145) and low-risk arms (n=83) according to the ratio of CD4/CD8 in allografts. Patients of the high-risk arms were randomly assigned in a 1:1 ratio to additional low-dose glucocorticoid prophylaxis group (Group A, n=72) and control group (GroupB, n=73). The groups were balanced with respect to patient and donor characteristics. Our results showed that the cumulative incidence of grade II-IV acute GVHD on day 100 was 20.9%±4.8% in Group A, which was comparable to Group C (25.5%±4.8%, P=0.430) and both of which were significantly lower than that of Group B (48.1%±5.9%, P＜0.001). In addition, the onset time of grade II-IV acute GVHD was 25 (16-50) days, 15 (9-57) days, and 21 (10-58) days, respectively in Group A, Group B, and Group C (P＜0.05, Group A vs. Group B or Group C). There were no significant difference in grade Ⅲ-IV acute GVHD among these three groups. The ratio of patients who developed glucocorticoid refactory acute GVHD and treated with basiliximab (anti-CD25 antibody) were 13.9% (10/72), 17.8% (13/73), and 22.9% (19/83), respectively, in Group A, Group B, and Group C, there is a trend that the incidence of basiliximab treated patients in Group C is higher than that of Group A (P=0.109). The median time for myeloid engraftment in Group A was 11 days (range: 10-21 days), which was significantly faster that those of Group B (13 days, range from 10 to 33 days, P＜0.05) and Group C (13 days, range from 10 to 33 days, P＜0.05). The median time for platelet engraftment in Group A was 12 days (range: 10-22 days), which was significantly faster that those of Group B (17 days, range from 6 to 255 days, P＜0.01) and Group C (19 days, range from 8 to 260 days, P＜0.01). In addition, risk-stratification directed prophylaxis with additional low-dose of MP did not increase the incidence of CMV, EBV reactivation, PTLD, relapse and TRM, as well as delay immune recovery after unmanipulated haploidentical HSCT. The 100 day cumulative incidence relapse and transplant-related mortality was not significantly different among patients in Group A, Group B, and Group C, respectively. The 100 day probabilities of LFS and OS were comparable among these three patient groups. In conclusion, we for the first time demonstrated that risk-stratification directed prophylaxis for GVHD with additional low-dose of MP could significantly decrease the incidence and delay the onset of grade II-IV acute GVHD without increasing infections and delaying immune recovery. Our data indicated that addition of glucocorticoid early after unmanipulated haploidentical transplantation could also accelerate hematopietic recovery [This study was registered at http://clinicaltrials.gov/ NCT01607580] . Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.40.40
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 23
    Online Resource
    Online Resource
    Prolonged Thrombocytopenia After Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) and Its Association with an Increase in CD8+ CX3CR1+ Cells in Bone Marrow.
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 3077-3077
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3077-3077
    Abstract: Abstract 3077 Background: Since prolonged thrombocytopenia (PT) is an independent risk factor for poor clinical outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the underlying mechanisms need to be understood in order to develop selective treatments. Previous studies1–4 have suggested that abnormalities in B cells may play a role in the pathogenesis of PT. However, abnormalities in B cells alone do not fully explain the complete pathogenic mechanisms of PT. Our previous studies5 showed that the frequency of megakaryocytes with a ploidy value ≤ 8N was significantly increased in patients who developed PT after allo-HSCT compared to the control group. Mechanisms concerning the megakaryocyte hypoplasia in PT after allo-HSCT are not well understood. Design and Methods: PT was defined as a platelet count ≤80 × 109/L for more than 3 months after HSCT, recovery of all other cell counts, and no apparent cause for thrombocytopenia, such as aGVHD, disease recurrence, CMV infection, or antiviral drug treatment at three months post-HSCT when all other blood cell counts had return to normal.5 We analyzed T cell subsets in bone marrow (BM) and peripheral blood (PB) from allo-HSCT recipients with and without PT (n = 23 and 17, respectively) and investigated the expression characteristics of homing receptors CX3CR1, CXCR4 and VLA-4 by flow cytometry. Futhermore, Mononuclear cells (MNCs) from PT patients and controls were cultured with and without autologous CD8+ T cells in vitro, and clarify the effect of activated CD8+ T cells on the ploidy and apoptosis of megakaryocytes in the bone marrow. Results: The results demonstrated that the percentage of CD3+ T cells in the BM was significantly higher in PT patients than the experimental controls (76.00 ± 13.04% and 57.49 ± 9.11%, respectively, P 〈 0.001), whereas this difference was not significant for the PB (71.01 ± 11.49% and 70.49 ± 12.89%, respectively, P = 0.911). While, some T cell subsets in the BM and PB from allo-HSCT recipients with PT were not significantly different from that of the experimental control group, such as CD8+ T cells, CD4+ T cells, CD4+ CD25bright T cells (regulatory T cells), CD44hi CD62Llo CD8+ T cells and naive T cells (CD11a+ CD45RA+). Furthermore, the surface expression of homing receptor CX3CR1 on BM T cells (64.16 ± 14.07% and 37.45 ± 19.66%, respectively, P 〈 0.001) and CD8+ T cells (56.25 ± 14.54% and 35.16 ± 20.81%, respectively, P = 0.036), but not in blood, were significantly increased in PT patients compared to controls. For these two groups of patients, the surface expression of CXCR4 and VLA-4 on T cells and CD8+ T cells from both BM and PB did not show significant differences. Through the study in vitro, we found that the activated CD8+ T cells in bone marrow of patients with PT might suppress apoptosis (MNC group and Co-culture group: 18.02 ± 3.60% and 13.39 ± 4.22%, P 〈 0.05, respectively) and Fas expression (MNC group and Co-culture group: 21.10 ± 3.93 and 15.10 ± 2.33, P 〈 0.05, respectively) of megakaryocyte. In addition, megakaryocyte with a ploidy value ≤ 8N (MNC group: 40.03 ± 6.42% and 24.54 ± 4.31%, respectively, P 〈 0.05) was significantly increased in patients with PT compared to the control group. Conclusions: In conclusion, an increased surface expression of CX3CR1 on T cells may mediate the recruitment of CD8+ T cells into the bone marrow in patients with PT who received an allo-HSCT. Moreover, CD8+CX3CR1+ T cells, which can have significantly increased numbers in bone marrow of patients with PT, likely caused a reduction in the megakaryocyte ploidy, and suppressed megakaryocyte apoptosis via CD8+ T cell-mediated cytotoxic effect, possibly leading to impaired platelet production. Therefore, treatment targeting CX3CR1 should be considered as a reasonable therapeutic strategy for PT following allo-HSCT. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.3077.3077
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 24
    Online Resource
    Online Resource
    Impact of Cytogenetic and Molecular Markers on Disease-Free Survival of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 3217-3217
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3217-3217
    Abstract: Introduction: Cytogenetics is an independent prognostic factor in acute myeloid leukemia (AML). Molecular genetics including leukemia fusion gene, gene mutation and gene over expression are recognized to have significant impact on survival in patients with AML as well. In present study, the impact of cytogenetic and molecular markers on disease-free survival (DFS) of allogeneic hematopoietic stem cell transplantation (HSCT) for AML was investigated. Methods: Between April 2012 and December 2014, consecutive 345 patients with AML who underwent allogeneic HSCT in our center were analyzed retrospectively. All patients were either in poor-risk or in good-risk/intermediate-risk but with persistent minimal residual disease. The median age was 19 (1.8 to 64) years old. Children (≤14 years) were 96 (27.8%) cases and adults ( 〉 14 years) were 249 (72.2%) cases. Male to female was 200:145. The median disease course was 6 (1-64) months. Leukocyte count at diagnosis was 〈 30 x 109/L in 230 (66.7%) patients (low leukocyte) and ≥30 x 109/L in 115 (33.3%) cases (high leukocyte). Transplants at CR1, ≥CR2, and advanced disease were 168 (48.7%), 53 (15.4%) and 124 (35.9%), respectively. Donor sources were identical sibling (IS) in 45 (13.0%) cases, unrelated (UR) in 71 (20.6%) cases and haploidentical (HI) in 229 (66.4%) cases. Myeloablative conditioning regimens were administered with either Busulfan (Bu) plus Cyclophosphamide (Cy)/Fludarabine (Flu)-based in 285 (82.6%) patients or total body irradiation (TBI) plus Cy/Flu-based in 60 (17.4%) patients. Antithymocyte globulin was used in unrelated and haploidentical HSCT. Unmanipulated bone marrow and peripheral blood stem cells (PBSC) for IS and HI HSCT and PBSC for UR transplant were applied as the grafts. Cyclosporine, short-term Methotrexate, and Mycophenolate mofetil were employed for GVHD prophylaxis. Results: Univariate analysis showed that DFS after allogeneic HSCT in AML was not associated with patient age (children vs. adults, 70.3% vs. 69.4%, p=0.6), leukocyte count at diagnosis (low leukocyte vs. high leukocyte, 68.8% vs. 71.3%, p=0.8), donor source (IS vs. UD vs. HI, 77.3% vs. 76.8% vs. 65.8%, p=0.21), and conditioning regimen (Bu-based vs. TBI-based, 70.1% vs. 67.3%, p=0.45). Multivariate analysis indicated that disease status before HSCT was the only impact factor on DFS (CR1 vs. ≥CR2 vs. advanced disease, 81.6% vs. 70.0% vs. 53.1%, p 〈 0.0001). Therefore, total 221 of 345 patients with AML in complete remission pre-conditioning were analyzed for impact of cytogenetic and molecular markers on survival after HSCT. DFS rates were 79.1%, 80.4%, 74.1% in good-risk, intermediate-risk, poor-risk cytogenetics groups (p=0.81), respectively. According to gene mutations, the DFS rates were 100% in CEBPA+, 91.6% in IDH1+/NPM1+, 85.7% in Flt3-ITD+, 81.5% in c-KIT+, 75.0% in no mutation, 70.2% in MLL-PTD+/ASXL1+/TET2+, 54.3% in Flt3-ITD+ with other mutations (p=0.42). According to gene expression, the DFS rates were 100% in DEK-CAN+, 100% in HOX11+/EVI1+, 84.8% in no abnormal gene expression, 83.3% in CBFb-MYH11+, 78.5% in WT1+, 76.5% in MLL+, 74.9% in AML1-ETO+, 0% in TLS-ERG+ (p=0.004). Conclusions: Under our HSCT protocol, disease status before transplant for the patients with AML has significant impact on DFS but not patient age, leukocyte count at diagnosis, donor source and conditioning regimen. Allogeneic HSCT has attenuated the influence of cytogenetics on DFS in patients with AML. Our preliminary data have shown that patients with CEBPA+, IDH1+/NPM1+, DEK-CAN+, HOX11+/NPM1+ have favorable survival, but patients with both Flt3-ITD+ and other gene mutations or with TLS-ERG+ have poor survival after allogeneic HSCT in AML. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.3217.3217
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
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  • 25
    Online Resource
    Online Resource
    Improved Outcomes of Haploidentical Blood and Marrow Transplantation in Hematologic Malignancies: A Single Center Study of 514 Cases
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 3224-3224
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3224-3224
    Abstract: Introduction: With GIAC regimen, haploidentical blood and marrow transplantation (haplo-BMT) has achieved comparable outcomes with identical sibling transplant (Dao-Pei Lu et al., Blood 2006; 107:3065). Our previous study has shown that the third party cell co-infusion in haplo-BMT (GIAC-3 regimen) could significantly reduce aGVHD and transplant-related mortality (TRM). We have also demonstrated that individualized chemotherapy to decrease leukemia burden followed by conditioning could improve disease-free survival (DFS) in refractory/relapsed AML. Objective: To learn the outcomes of our haplo-BMT with these integrated approaches, all patients who received haplo-BMT for hematologic malignancies in our center were analyzed retrospectively. Methods: Between April 2012 and December 2014, consecutive 514 patients with hematologic malignancies who underwent haplo-BMT were included. The median age was 20 (1.8 to 64) years old. The diagnosis included AML 232 (45.1%), ALL 207 (40.3%), MDS 27(5.3%), CML 14 (2.7%), lymphoma 13 (2.5%) and others 21 (4.1%). Transplants at CR1, ≥CR2 or advanced disease were 216 (42.0%), 114 (22.2%), 184 (35.8%), respectively. All patients received unmanipulated bone marrow (BM) and peripheral blood stem cells as graft after myeloablative conditioning plus ATG. Majority of the patients with AML received BuCy-based conditioning, while most ALL patients received TBICy-based regimen. Fludarabine was substituted for cyclophosphamide in some patients due to impaired organ function or high tumor burden. For refractory/relapsed diseases, individualized chemotherapy followed by conditioning was administered. Cyclosporine/tacrolimus, short-term Methotrexate, and Mycophenolate mofetil were employed for GVHD prophylaxis. Either 1ml/kg (recipient's body weight) haploidentical BM from the second haploidentical donor or one unit of unrelated cord blood was infused right after haplo-BMT as the third party cells. Minimal residual disease (MRD) was monitored routinely by quantitative PCR or flow cytometry. The patients with persistent MRD were interfered by immunosuppressant withdrew, adoptive immunotherapy with cytokine induced killer or NK cells or donor lymphocyte infusion. Results: All patients but 5 achieved durable engraftment. The cumulative incidences of grade II to IV aGVHD and grade III to IV aGVHD were 32.2%, 19.8%, respectively. The cumulative incidences of cGVHD and extensive cGVHD were 48.3%, 18.4%, respectively. 100-day TRM and 2-year TRM were 4.1%, 14.9%, respectively. Two-year relapse rate was 22.8%. With the median follow up 17 (6 to 38) months, overall 2-year DFS rates in CR1, ≥CR2 and advanced disease were 75.6%, 70.9%, 49.2%, respectively. For AML, two-year DFS rates in CR1, ≥CR2 and advanced disease were 74.1%, 76.9%, 48.2% (CR1 vs. ≥CR2, p=0.84; CR vs. advanced disease, p=0.000). For ALL, two-year DFS rates in CR1, ≥CR2 and advanced disease were 78.9%, 56.6%, 38%, respectively (CR1 vs. ≥CR2, p=0.018; CR1 vs. NR, p=0.000; ≥CR2 vs. NR P=0.02 ). Conclusions: With our strategies, overall outcomes of haplo-BMT have been improved remarkably and very encouraging. Therefore, haplo-BMT should be an important way to save life for the patients with hematologic malignancies who need urgent BMT but without matched either sibling or unrelated donor. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.3224.3224
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 26
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    Online Resource
    Machine-Learning Based Early Warning System for Prediction for Disseminated Intravascular Coagulation after Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Multicenter Study
    American Society of Hematology ; 2021
    In:  Blood Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2113-2113
    Details
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2113-2113
    Abstract: Introduction Allogeneic haematopoietic stem cell transplantation (allo-HSCT) has been demonstrated to be the most effective therapy for various malignant as well as nonmalignant haematological diseases. The wide use of allo-HSCT has inevitably led to a variety of complications after transplantation, with bleeding complications such as disseminated intravascular coagulation (DIC). DIC accounts for a significant proportion of life-threatening bleeding cases occurring after allo-HSCT. However, information on markers for early identification remains limited, and no predictive tools for DIC after allo-HSCT are available. This research aimed to identify the risk factors for DIC after allo-HSCT and establish prediction models to predict the occurrence of DIC after allo-HSCT. Methods The definition of DIC was based on the International Society of Thrombosis and Hemostasis (ISTH) scoring system. Overall, 197 patients with DIC after allo-HSCT at Peking University People's Hospital and other 7 centers in China from January 2010 to June 2021 were retrospectively identified. Each patient was randomly matched to 3 controls based on the time of allo-HSCT (±3 months) and length of follow-up (±6 months). A lasso regression model was used for data dimension reduction, feature selection, and risk factor building. Multivariable logistic regression analysis was used to develop the prediction model. We incorporated the clinical risk factors, and this was presented with a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal and external validation was assessed. Various machine learning models were further used to perform machine learning modeling by attempting to complete the data sample classification task, including XGBClassifier, LogisticRegression, MLPClassifier, RandomForestClassifier, and AdaBoostClassifier. Results A total of 7280 patients received allo-HSCT from January 2010 to June 2021, and DIC occurred in 197 of these patients (incidence of 2.7%). The derivation cohort included 120 DIC patients received allo-HSCT and 360 patients received allo-HSCT from Peking University People's Hospital, and the validation cohort included the remaining 77 patients received allo-HSCT and 231 patients received allo-HSCT from the other 7 centers. The median time for DIC events was 99.0 (IQR, 46.8-220) days after allo-HSCT. The overall survival of patients with DIC was significantly reduced (P ＜ 0.0001). By Lasso regression, the 10 variables with the highest importance were found to be prothrombin time activity (PTA), shock, C-reactive protein, internationalization normalized ratio, bacterial infection, oxygenation, fibrinogen, blood creatinine, white blood cell count, and acute respiratory distress syndrome (from highest to lowest). In the multivariate analysis, the independent risk factors for DIC included PTA, bacterial infection and shock (P & lt;0.001), and these predictors were included in the clinical prediction nomogram. The model showed good discrimination, with a C-index of 0.975 (95%CI, 0.939 to 0.987 through internal validation) and good calibration. Application of the nomogram in the validation cohort still gave good discrimination (C-index, 0.778 [95% CI, 0.759 to 0.766]) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. The predictive value ROC curves of different machine learning models show that XGBClassifier is the best performing model for this dataset, with an area under the curve of 0.86. Conclusions Risk factors for DIC after allo-HSCT were identified, and a nomogram model and various machine learning models were established to predict the occurrence of DIC after allo-HSCT. Combined, these can help recognize high-risk patients and provide timely treatment. In the future, we will further refine the prognostic model utilizing nationwide multicenter data and conduct prospective clinical trials to reduce the incidence of DIC after allo-HSCT and improve the prognosis. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2021-150437
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 27
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    Exome Sequencing Identifies Somatic Mutations of DDX3X in Natural Killer/T-Cell Lymphoma
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 1663-1663
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1663-1663
    Abstract: Natural-killer/T cell lymphoma (NKTCL) is a malignant proliferation of CD56+/cytoCD3+ lymphocytes and constitutes a heterogeneous group of aggressive lymphoma prevalent in Asian and South American populations. NKTCL represents a distinct clinicopathologic entity of non-Hodgkin’s lymphoma, characterized by male predominance, strong association with Epstein-Barr virus (EBV) infection, prominent tissue necrosis and aggressive clinical course. However, molecular pathogenesis of NKTCL remains largely elusive. Here we identified somatic mutations by whole-exome sequencing in 25 NKTCL patients and extended validation through targeted sequencing in an additional 80 cases. Functional experiments including RNA unwinding test, colony forming assay, cell proliferation assay and gene expression profiling were also performed. Overall, 50.5% of NKTCL patients displayed somatic mutations of RNA helicase family, tumor suppressors (TP53 and MGA), and/or epigenetic modifiers (MLL2, ARID1A, EP300 and ASXL3). Recurrent mutations were most frequently discovered in RNA helicase gene DDX3X (21/105 cases, 20.0%). Mutations of DDX3X were seldom overlapped with those of TP53. Functionally, DDX3X mutants exhibited reduced RNA unwinding activity and enhanced cell proliferation. Similar stimulatory effect on cell proliferation was observed in cells transfected with specific siRNA targeting DDX3X. Gene expression profiling revealed an association of DDX3X mutations with activation of NF-kB and MAPK pathways. The clinical follow-up data showed that DDX3X-mutated patients presented a poor prognosis. Our work suggests the heterogeneity of gene mutational spectrum of NKTCL and provides a potential therapeutic target for relevant cases. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.1663.1663
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 28
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    Overexpression of WT1 and PRAME predicts poor outcomes of patients with myelodysplastic syndromes with thrombocytopenia
    American Society of Hematology ; 2019
    In:  Blood Advances Vol. 3, No. 21 ( 2019-11-12), p. 3406-3418
    Details
    In: Blood Advances, American Society of Hematology, Vol. 3, No. 21 ( 2019-11-12), p. 3406-3418
    Abstract: Overexpression of WT1 and PRAME are common in MDS patients with thrombocytopenia. Both are independent poor prognostic factor for outcome. The evaluation of WT1/PRAME transcript analysis can better risk-stratify the patients, thus guiding individualized treatment.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    URL: Article
    DOI: 10.1182/bloodadvances.2019000564
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 2876449-3
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  • 29
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    Imatinib Mesylate Versus Allogeneic HSCT for Patients with Chronic Myelogenous Leukemia In Accelerated Phase: A Single Center Experience In China After a 9-Year Follow-up
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 2347-2347
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2347-2347
    Abstract: Abstract 2347 The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the imatinib era in patients with chronic myelogenous leukemia (CML) in accelerated phase (AP) has not been evaluated due to few comparison study published. A prospective study was designed to compare the outcome of imatinib versus allo-HSCT for AP CML according to the World Health Organization (WHO) 2001 classification in our center (Registration Number: ChiCTR-TNC-10000955). In imatinib group, imatinib were given at an initial dose of 400 mg or 600 mg daily. In allo-HSCT group, the recommended treatment prior to transplantation was a short-term imatinib therapy less than 3 months. From April 2001 to September 2008, 132 patients were enrolled, 87 in imatinib group and 45 in allo-HSCT group, respectively, according to their intention. In allo-HSCT group, 19 patients performed transplant from a HLA-matched sibling donor, 23 from a HLA-mismatched sibling/haploidentical donor, and 3 from a HLA-mismatched unrelated donor. The end time of evaluation was April 2010. After a median follow-up of 45 months (range, 7–108 months) for 53 living patients on imatinib and 65 months (range, 18–108 months) for 38 living patients post allo-HSCT, imatinib was inferior to allo-HSCT in outcome, with the estimated 6-year event-free survival (EFS), overall survival (OS) and progression-free survival (PFS) rates of 39.2% vs 71.7% (P=0.035), 51.4% vs 83.3% (P=0.023), and 48.3% vs 95.2% (P=0.000), respectively. A multivariate analysis of the total population of 132 patients adding pretreatment characteristics and therapy (imatinib versus allo-HSCT) indicated that longer CML disease duration, pretreatment anemia and higher percentage of peripheral blasts were independent adverse prognostic factors for OS and PFS in common, imatinib therapy was only associated with shorter PFS. In order to analyze whether therapy play an important role in survival differences among patients with or without common pretreatment poor prognostic factors for OS and PFS, we categorized the entire cohort into low-risk (neither factor, n=40), intermediate-risk (either factor, n=59) or poor-risk (at least two factors, n=33). Therapy had no influence on the outcome in low-risk patients, with the estimated 6-year EFS, OS and PFS rates of 80.9% vs 80.7% (P=0.898), 100% vs 81.2% (P=0.114), and 85.2% vs 95.2% (P=0.365), in imatinib group vs allo-HSCT group, respectively. EFS and OS showed no difference by therapy in intermediate-risk patients, with the estimated 6-year EFS and OS rates of 47.1% vs 61.9% (P=0.788), and 61.3% vs 81.3% (P=0.773), in imatinib group vs allo-HSCT group, respectively. However more patients developed a relapse in advanced phase with imatinib compared to those with allo-HSCT, the estimated 6-year PFS rates were 55.7% vs 92.9% (P=0.047), respectively. The superiority of allo-HSCT was extremely significant in poor-risk patients, with the estimated 5-year EFS, OS and PFS rates of 9.3% vs 66.7% (P=0.034), 17.7% vs 100% (P=0.008) and 18.8% vs 100% (P=0.006), in imatinib group vs allo-HSCT group, respectively. We conclude that allo-HSCT is the first-line option for all patients with CML in AP; it is superior to imatinib with evident survival advantage for poor/intermediate-risk patients. However, the outcome of imatinib and allo-HSCT were equally good in low-risk patients with CML in AP. For such patients, it may also be advised that imatinib remains the primary option by carefully monitoring of MRD, and allo-HSCT may be considered if there is evidence of imatinib resistance. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.2347.2347
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 30
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    The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment
    American Society of Hematology ; 2023
    In:  Blood Vol. 142, No. 10 ( 2023-09-07), p. 903-917
    Details
    In: Blood, American Society of Hematology, Vol. 142, No. 10 ( 2023-09-07), p. 903-917
    Abstract: The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.2022019537
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2023
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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