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  • 1
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4897-4897
    Abstract: Xiaomei Chen and Jianyu Weng contributed equally to this study. The outcomes ofrelapsed or refractory acute myeloid leukemia (RR-AML) are poor and effective salvage regimens are urgently needed. We present a study of 14 patients with RR-AML (median age 42years, range 18-65years; male n=12, female n= 2) treated with CLAT regimen, which consisted of cladribine 5mg/m² per day i.v. 2-3 hour on days 1-5, cytarabine 1.0g/m² per day i.v. 4 hours after cladribine on days 1-5, topotecan 1.25mg/m² per day i.v. 4 hours after cytarabine on days1-5 and G-CSF 300ug per day subcutaneous injection on days until neutrophile granulocyte recovery. Total of fourteen patients were included into the study from June 2013 to June 2015, Two (14.3%) patients were relapsed and twelve (85.7%) patients were refractory, 4 of 14 patients were relapsed or refractory after allogeneic-HSCT. Two patients died of invasive fungal infection before the assessment. Seven patients (58.3%) achieved complete remission (CR), and one patient (8.3%) achieved partial remission (PR), the rest patients (33.3%) did not respond (NR). The overall response rate was 66.7%. Following CLAT treatment, four patients with CR underwent allogeneic hematopoietic stem cell transplantation (HSCT) or microtransplantation. The median relapse-free survival (RFS) for RR-AML patients receiving CLAT regimen was 8.6 (range 2-16) months. Thirteen patients developed grade 4 granulocytopenia and thrombocytopenia, the median duration was 13(range 2 to 21) days and12 (range 2 to 21) days, respectively. The most common non-hematological side effects included nausea, vomiting, diarrhoea, and were grade 1/2. The CLAT regimen seems promising for the treatment of patients, and it was well tolerated. This regimen offers an alternative treatment for those patients with RR-AML who have received severe intensive treatment, especially with anthracycline-containing chemotherapy. The project was sponsored by grants from National Natural Science Foundation of China (No. 30972790; No.81270648; No.81370665; No.81300446) Provincial Natural Science Foundation of Guangdong (No. S2012010009560) Provincial Science and Technology Planning Project of Guangdong (No.2013B021800186; No.2013B021800201), and Science and Technology Planning Project of Guangzhou (No. 201400000003-4, 201400000003-1). Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 2
    In: Leukemia, Springer Science and Business Media LLC, Vol. 34, No. 10 ( 2020-10), p. 2790-2793
    Type of Medium: Online Resource
    ISSN: 0887-6924 , 1476-5551
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2008023-2
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  • 3
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-9-2)
    Abstract: The t(11;14)(q13;32) is a common chromosome translocation in multiple myeloma (MM), but its prognostic value remains controversial. Immunoglobulin light chain amyloidosis is commonly secondary to multiple myeloma, which can rapidly cause heart failure and high mortality. We aimed to investigate the prevalence of secondary cardiac amyloidosis in MM patients with t(11;14) and to evaluate its impact on survival outcomes. Methods We retrospectively identified 52 MM patients with t(11;14) in our center between October 2015 and April 2022. The associations between cardiac amyloidosis and clinical and biological parameters were statistically analyzed, and the impacts of concomitant of cardiac amyloidosis on survival and prognosis of MM patients with t(11;14) were also assessed. Results Concomitant presence of cardiac amyloidosis was observed in 15 (28.8%) of all cases. Patients with cardiac amyloidosis had significantly higher NT-proBNP ( p = 0.002) and higher hs-cTnT ( p & lt; 0.001), while the patients without cardiac amyloidosis had higher percentage of bone marrow plasma cells ( p = 0.027), higher incidence of hemoglobin & lt;80 g/L ( p = 0.021) and bone destruction ( p & lt; 0.001). The median overall survival (OS) for all patients was 33.4 months after a median follow-up of 23.8 months. The amyloidosis group showed a significantly shorter OS than the non-amyloidosis group (15.3 vs. 41.8 months, p & lt; 0.001). Besides, patients harboring NT-proBNP & gt;1,800 pg/ml ( p & lt; 0.001) or hs-cTnT ≧40 pg/ml ( p = 0.001) or light chain (LC) only isotype ( p = 0.033) had a significantly shorter mean OS compared with patients with lower NT-proBNP or hs-cTnT or other M-protein isotype. Univariate analyses showed that NT-proBNP & gt;1,800 pg/ml, hs-cTnT ≧40 pg/ml, LC only isotype, and concomitant presence of cardiac amyloidosis were independently associated with shorter OS, while NT-proBNP & gt;1,800 pg/ml still retained the prognostic value for OS in multivariate analyses. Conclusion The t(11;14) MM patients with coexisting cardiac amyloidosis may represent a distinct clinical entity that confers a poor outcome. These findings may have important clinical and biological implications.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5082-5082
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5082-5082
    Abstract: BACKGROUND & OBJECTIVE FMyelodysplastic syndromes (MDS) are among the most frequent hematologic malignancies. The diagnosis of MDS can be difficult, and there is a paucity of molecular markers. The pathophysiology is still largely unknown. Therefore, we investigated whether serum proteome profiling may serve as a noninvasive platform to discover novel molecular markers for MDS and establish the predictive models that may be of help to serologic diagnosis and classification of MDS. METHODS FSerum samples were collected from 14 MDS patients including to 8 Refractory anemia with excess blasts in transformation (RAEB) and 6 Refractory cytopenia with multilineage dysplasia (RCMD) and 18 non-MDS hematologic malignancies and 8 age- and sex-matched healthy subjects. Serum peptides were separated and purified with a purification kit of magnetic beads, using magnetic beads-based weak cation exchange chromatography (MB-WCX) and MB-IMAC Cu, bases on immobilized metal ion affinity chromatography on the surface of superparamagnetic microparticles. We generated serum proteome profiles by matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF- MS) and identified a profile that distinguishes MDS from non-MDS hematologic malignancies and healthy subjects. RESULTS FA totaI of 146 effective protein peaks were detected at the molecular range of 1.02 tO 10.25 ku, Among which 7 protein peaks were different significantly among MDS patients, non-MDS hematologic malignancies and healthy subjects (P & lt;0.05). There was also different for Peptide mass fingerprinting in MDS patients, and the samples were divided into two groups, which was identical with clinical classification about RAEB and RCMD, using 3-cross validation approach. There was significantly different expression protein between RCMD and RAEB patients, which was identified as a piece of fibrinogen peptide. The expressions of fibrinogen in RAEB subtype patients were higher than RCMD subtype patients. CONCLUSION F Using the MALDI-TOF-MS technique may help to identify serum proteomic biomarkers related to MDS. The predictive models can discriminate MDS patients from other hematologic malignancies and healthy people effectively and help to identify MDS clinical classification. The different expression of Fibrinogen between RAEB and RCMD may suggested heterogeneity of etiopathogenisis in different subtypeof MDS.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 5
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1147-1147
    Abstract: Abstract 1147 Poster Board I-169 In the past twenty years, allogeneic hematopoietic stem cells transplantation (Allo-HSCT) has been accepted as the most effective treatment for many hematologic malignancies. However, the successful rate of allo-HSCT has been limited by transplantation-related mortality and malignancies relapse, no matter using traditional intensity conditioning or reduced-intensity conditioning. In this study, we presented ninety-two patients with hematopoietic malignancies received fludarabine combinasion with modified Bu/Cy (FABC) conditioning regimen before allogeneic hematopoietic stem cell transplantation. Ninety-two patients with hematological malignancies (58 males, 34 females) ranged in age from 14 to 50 (median 28) years. These patients were diagnosed with acute lymphoblastic leukemia (ALL, n=30), acute myelogenous leukemia(AML, n=24), chronic myelogenous leukemia (CML, n=33; CP, n=27; CML-AP, n=5; CML-BC, n=1), myelodysplastic syndrome ( MDS, n=3), chronic myelomonocytic leukemia (CMML, n=1), and one patient coexisted chronic myelomonocytic leukemia and T lymphoblast cell lymphoma. Fifty-five (59.8%) patients were at high risk. From June 2004 to October 2008, 92 patients gave their informed consent and received conditioning regimen with fludarabine-based modified Bu/Cy (FABC conditioning regimen) in allo-HSCT. The FABC regimen consist of cytarabine 2.0 g/ m2 on day -9, busulphan (Bu) 3.2 mg/kg per day for intravenous on days -8 to day-6, followed by cyclophosphamide (Cy) 60 mg/kg per day on days -5 and day-4, combined fludarabin 30 mg/m2 per day for three consecutive days, on days -6 to day-4, and Me-CCNU (1-(2-Chloroethyl)-3-(4-ethylnitrobiphenyl Cylohexyl4)-1- Nitrosourea) 250 mg/m2 on day -3. Graft-versus-host-disease(GVHD) prophylaxis consisted of cyclosporine A, short-term MTX and Mycophenolate Mofefil (MMF 1.0g/day, on d-8 to d-1). Anti-T-lymphocyte globulin (2.5 mg·kg-1·d -1, on d-3 to d-1) was added to patients with mismatched sibling or unrelated donors. Follow-up was performed on 30 December, 2008. Ninety-two patients engrafted successfully, the median time for ANC 〉 0.5×109/L was 12 (8 to 22) days, and for BPC 〉 20×109/L was 12 (7 -32) days. Detected by short tandem repeat (STR)-PCR, complete donor chimerism was comfirmed in all patients on day +21 or day+30. The incidence of acute GVHD was 25% (23/92), and grades 3 to 4 acute GVHD developed in 8 (8.7%) of 92 patients with in 100 days after HSCT. Chronic GVHD developed in 40(47.6%) of 84 patients who were alive more than 100 days after HSCT, and the incidence of extensive cGVHD was 35.7%(30/84). The transplant related mortality (TRM) was 19.6% (18/92), mainly from severe infection (n=7), acute or chronic GVHD (n=5), transplant associated-microangiopathy (n=2), diffusion alveolar hemorrhage (n=2), and post-transplant lymphoproliferative disorders (n=2). With a median follow-up of 16.2(1.5 to 54.5) months, 70 (76.1%) of the 92 patients were alive and 67(72.8%) were disease-free. The probabilities of OS at 1 year and 2 years was 80% and 72.5%, and DFS was 79.1% and 71.4%, respectively. These results suggest that the fludarabine-based modified Bu/Cy conditioning regimen (FABC) should reduce severe acute GVHD and accelerate hematopoietis resconsition without increasing chronic GVHD and lower leukemia relapse rates even in high-risk patients. Footnotes Corresponding author Disclosure No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 6
    Online Resource
    Online Resource
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 4921-4921
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4921-4921
    Abstract: Introduction The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem cell disorders, while, immunological abnormalities are frequently observed in patients with MDS[1]. Several reports [2,3] revealed that about 10% of MDS patients have clinical autoimmune disorders like skin vasculitis, rheumatic disease, or autoimmune hemolytic anemia. Furthermore, serological immunological abnormalities like hyper- or hypogammaglobulinemia, positivities of antinuclear antibody, positivities of direct Coombs test, or inverted CD4/8 ratios were found in 18–65% of patients with MDS. Recently immunosuppressive therapies including prednisolone, antithymocyte globulin, and cyclosporin A (CsA) are used to treat cytopenia in some patients with MDS. We reported four patients with MDS. Rearrangements of the TCR-beta genes were seen in these patients using RT-PCR and Genescan analysis (CDR 3 length analysis). Also they had skewed TCR usages using TCR repertoire analysis. Methods Two patients with refractory anemia(RA), two with refractory anemia with blasts(RAEB). four males from 41to 68 yearsold. Complementarity determining region 3(CDR3) of TCR Vβ with 24 variable region gene was amplified in peripheral blood mononuclear cells, which were drawn from five patients with myelodysplastic syndromes (MDS) using RT-PCR, to observe the expression of TCR Vβreceptoroire T cells, the PCR products were further analyzed by genescan to evaluating clonality of T cells (CDR 3 length analysis), and compare results with age-matched healthy donors and patients with graft versus host disease(GVHD). Results We found a significantly higher number of skewed Vb profiles in the MDS and GVHD patients compared with donors. In peripheral blood T cells, Only 2-11 Vb subfamily T cells could be identified in MDS patinets, clonal expansion T cells could be found in Vb1, 3,13, 14 and 21 subfamilies. Disussion In this study, we evaluated the total T-cell repertoire of 4 MDS patients using gendscan analysis to look for evidence of T-lymphocyte clonality. This analysis showed that all 4 patients exhibited extensive skewing of their TCR spectratypes, suggesting clonal or oligoclonal T-cell expansions. Epperson [10]also reported the same results. As we know, acute and chronic graft-versus-host disease(GVHD) is a major complication after allogeneic bone marrow transplantation. GVHD is mediated by T cells that are derived from the BM graft. In this study, we compared the results of GVHD patients with that of MDS patients, and found that these two groups patients show TCR Vb skew distribution and clonal expansion. These findings provide further evidence that T cell mediated immune processes are a feature of MDS.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
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  • 7
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5229-5229
    Abstract: Background: Treatment for acute myeloid leukemia (AML) has remained relatively unchanged over the past few decades. Standard-dose cytarabine and idarubicin (7+3 IA) or daunorubicin (7+3 DA) induction regimen have been recommended for AML induction therapy by global guidelines. Mitroxantrone, a type II topoisomerase inhibitor, disrupts DNA synthesis and DNA repair, has been recommended as a salvage treatment for refractory/relapsed AML or induction therapy for elderly patients. Objective: To compare the the clinical response and adverse events of Idarubicin regimen ( IA) with mitoxantrone and cytarabine (MA) in the treatment of newly acute myeloid leukemia (AML) . Methods: This retrospective study evaluated 164 patients with newly diagnosed AML who received either IA (idarubicin 10mg/M2, d1-3; cytarabine 200mg/d, d1-7) or MA regimen (mitoxantrone 10mg/M2, d1-d3; cytarabine 200mg/d, d1-7) as induction therapy from September 2010 to November 2017 at Guangdong General Hospital. The primary end point of this study was complete response and complete response with incomplete blood count recovery (CR/CRi), with secondary end points were adverse event rates and days of granulocyte and platelet recovery. Results: A total of 164 patients , 90 patients were males and 74 females, the median age was 41 (range:14~64) years old. There were 88 patients received IA regimen and 76 patients received MA regimen. There was no significant difference in clinical features and molecular biological characteristics in two groups (P 〉 0.05). The CR/CRi rate was 72.3% and 64.0% (P=0.263) in IA and MA group after the first induction regimen, respectively. And the accumulated CR/CRi rate was 85.9% and 75.7% in two group, respectively (P=0.109). The common adverse reactions in the two groups were myelosuppression and infection , but with no statistical difference (P 〉 0.05) in the incidence and grade of serious. The grade 4 and grade 5 neutropenia were 95.3% vs.98.7% and 4.7% vs. 1.3%, P 〉 0.05 in IA and MA group respectively. And thrombocytpenia were 72.9% vs.63.2% and 4.7% vs. 1.3%, P 〉 0.05. There was no significant difference in the incidence and severity of gastrointestinal, cardiovascular, respiratory, skin, liver and kidney injury between the two groups (P 〉 0.05). The median days of intravenous antibiotics (including antifungal drugs), neutrophil recovery, platelet recovery and the units of platelet and red blood cell suspension transfusion had no statistical difference in two groups (P 〉 0.05). Conclusion: This retrospective study implied mitoxantrone with standard-dose cytarabine (3+7 MA) regimen has similar efficacy and outcome to the idarubicin with standard-dose cytarabine (3+7 IA) regimen for newly diagnosed AML, without increasing the incidence of adverse event rates. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
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  • 8
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-11-2)
    Abstract: Identifying subgroups of T-cell acute lymphoblastic leukemia (T-ALL) with poor survival will significantly influence patient treatment options and improve patient survival expectations. Current efforts to predict T-ALL survival expectations in multiple patient cohorts are lacking. A deep learning (DL)-based model was developed to determine the prognostic staging of T-ALL patients. We used transcriptome sequencing data from TARGET to build a DL-based survival model using 265 T-ALL patients. We found that patients could be divided into two subgroups (K0 and K1) with significant difference (P & lt; 0.0001) in survival rate. The more malignant subgroup was significantly associated with some tumor-related signaling pathways, such as PI3K-Akt, cGMP-PKG and TGF-beta signaling pathway. DL-based model showed good performance in a cohort of patients from our clinical center (P = 0.0248). T-ALL patients survival was successfully predicted using a DL-based model, and we hope to apply it to clinical practice in the future.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 9
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-06-15)
    Abstract: C5aR signaling plays an important role in the regulation of T cell activation and alloimmune responses in chronic graft-versus-host disease (cGVHD). However, direct evidence of this modulation and the efficacy of C5aR blockade in the treatment of cGVHD have not been demonstrated. We observed higher expression of C5aR on both monocytes and T cells of patients with cGVHD compared with healthy controls and non-GVHD patients after allogeneic hematopoietic stem cell transplantation. Our data also demonstrated a significant negative correlation between C5aR expression and regulatory T cells (Treg) frequency in cGVHD patients, indicating a potential role of C5aR in the generation and regulation of Treg. In addition, an in vitro experiment revealed C5aR deficiency promoted the development of Treg whereas C5a activation abolished the differentiation of Treg. Importantly, we found C5aR blockade by PMX53 attenuated the pathology of cGVHD and improved the survival of cGVHD mice. PMX53 had a direct regulatory effect on Treg commitment and increased TGF-β1 expression. Thus, C5aR signaling may induce and intensify cGVHD by down-regulating Treg induction. The modulation of C5aR activation by PMX53 may provide a potential therapy for cGVHD.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 10
    Online Resource
    Online Resource
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4132-4132
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4132-4132
    Abstract: Abstract 4132 The objective was to definite the expression level of aven mRNA of white blood cells from peripheral blood(PB)of de novo acute myeloid leukemia and preliminary analyze its clinical significance, providing a experimental basis for evaluating prognosis. Aven mRNA levels in PB samples from 69 AML patients were detected by using real-time quantitative PCR. The relation of aven mRNA level with clinical and hematological characteristics (age, sex, WBC, Hb, Plt, LDH, Blast% in PB and BM,FAB subtype) and treatment outcome (complete remission rate and relapse rate)were analyzed. Twenty-one normal individuals served as controls. The level of aven mRNA was between 11.72% and 178.93 %(median 37.2%) in de novo AML and between 10.81% and 50.98 %(median 28.81%) in normal individuals. Aven mRNA level was higher in the AML group than in the controls (p=0.006). When we compared aven mRNA with other clinical and hematological parameters, there were significant correlations between aven mRNA and age(r=0.25,p=0.039),aven mRNA and hemoglobin level (r=0.29,p=0.019),aven mRNA and FAB subtype(r=0.253,p=0.036). We found that median level of aven mRNA in group whose age older than median age was higher than group whose age younger than median level(p=0.018).The complete remission rate after two cycles chemotherapy in group with lower aven mRNA level(25/30,83.33%)was higher than group with higher aven mRNA level(21/30,70%). But the difference was not significant(p=0.22).The difference of aven mRNA expression level between AML patients with relapse and that without relapse was not significant (p=0.076). In conclusions, the level of aven mRNA in de novo AML is overexpression. The overexpression of aven mRNA is likely to play an important role in tumorigenesis of AML. Association of aven mRNA expression with treatment outcome and relapse was not observed. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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