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  • American Society of Hematology  (20)
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  • 1
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 36-36
    Abstract: Abstract 36 Background. Nephrotic syndrome (NS) is frequently accompanied by thromboembolic complications such as renal vein thrombosis, deep vein thrombosis and pulmonary embolism. However, the cause of the hypercoagulable state in NS patients is not understood. In contrast to quiescent cells, membrane-derived microparticles have exposed phosphatidylserine which may support procoagulant enzyme complexes in thrombosis. Objectives. The aim of this work was to measure the type and quantity of MPs that expose PS in NS patients, and to evaluate the associated procoagulant activity (PCA). Methods. The subjects with membranous nephropathy (MN) or minimal change nephrotic syndrome (MCNS) were compared to healthy controls. Flow cytometry and confocal microscopy was used to evaluate microparticles. PCA was determined by clotting time and purified coagulation complex assays. Results. We found that the number of lactadherin+ MPs was significantly higher in each NS group MCNS (3230 ± 536)/MN (4642 ± 697) than that in the controls (1748 ± 239), furthermore, MPs in MN patients are significantly higher than ones in MCNS (P 〈 0.05; Table 1), which mostly derived from RBC and platelet membranes. The percentage of lactadherin+ RBCs was also significantly increased in each NS group, MN (9.7 ± 3.2%)/MCNS (5.1 ± 2.4%) patients compared to the controls (0.5 ± 0.2%). In addition, the mean percentage of lactadherin+ RBCs in MN showed significantly higher than that in MCNS (P 〈 0.05). In both NS groups, the percentage of lactadherin+ platelets was significantly higher than that in healthy control subjects (4.1 ± 1.1%) (P 〈 0.05 for both). Furthermore, patients in MN (11.5 ± 3.1%) also had significantly increased lactadherin+ platelets than in MCNS (7.3 ± 2.3%) (P 〈 0.05). By confocal laser-scanning microscope, nearly no staining by Alexa Fluro 488-lactadherin could be detected on RBCs or platelets membranes in healthy subjects, whereas a light green fluorescence on RBC and platelet with lactadherin accompanying vesiculation were observed in NS patients. PCA of RBCs/platelets from healthy individuals and NS patients was assessed by recalcification time assays, intrinsic, extrinsic FXa and prothrombinase assays. MPs shedding and PS exposure of RBCs/platelets were highly procoagulant in NS patients and blockade of PS with lactadherin inhibited over 90% of PCA. However, an anti-TF antibody had no significant inhibition effect (Figure 1). Conclusions. This is the first study to show that loss of RBCs/platelets membrane phospholipid asymmetry with increased PS exposure and MPs release may contribute to the hypercoagulable state of NS patients. The extent of PS exposure on cells and MPs may be a marker of thromboembolic risk in these patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 2
    In: Blood, American Society of Hematology, Vol. 142, No. Supplement 1 ( 2023-11-02), p. 6187-6187
    Abstract: Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by an excessive immune response. Beta-2 microglobulin (B2M) forms the light chain section of the major histocompatibility complex (MHC) class Ⅰ antigen. The prognostic role of B2M in lymphoma-associated HLH remains to be determined. This study was to investigate the prognostic role of serum B2M in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). Methods: The clinical and laboratory characteristics of adult patients in a multicenter cohort with lymphoma-associated HLH who had baseline serum B2M levels between August 2009 and June 2023 were retrospectively analyzed. The diagnosis of HLH was established according to the HLH-2004 criteria. Results: A total of 326 cases were included and the median serum B2M level was 5.19 mg/L. The most common subtype of lymphoma was T/NK cell lymphoma (51.8%, 169/326), followed by B-cell non-Hodgkin lymphoma (45.4%, 148/227) and Hodgkin lymphoma 8/326 (2.5). The optimal cut-off value of serum B2M for predicting overall survival was 8.73 mg/L (p & lt; 0.0001). Patients were divided into two subgroups by the optimal cut-off value. The median survival was 21 days for the high level subgroup, and 236 days for the low level subgroup (Figure 1). The 6-month survival rates were 22% and 54%, respectively. The subgroup with B2M level & gt; 8.73 mg/L was older and had a higher proportion of stage IV. Patients with higher levels of B2M showed lower levels of platelets, albumin, and fibrinogen, and high levels of creatinine. A moderate correlation between creatinine and serum B2M was found (Spearman's ρ = 0.417, p & lt; 0.001). The multivariate analysis showed that the high levels of serum B2M ( & gt; 8.73 mg/L) and creatinine (≥ 133 μmol/L), decreased fibrinogen (≤ 1.5 g/L), agranulocytosis ( & lt; 0.5×10 9/L), severe thrombocytopenia ( & lt; 50×10 9/L), and increased Epstein-Barr virus DNA were found to have significant prognostic values in all patients. The high serum B2M level ( & gt; 8.73 mg/L), severe thrombocytopenia ( & lt; 50×10 9/L), agranulocytosis ( & lt; 0.5×10 9/L), and high Epstein-Barr virus DNA copy number were independent prognostic factors in patients with creatinine & lt; 133 μmol/L. Finally, a prognostic scoring system was established based on serum B2M levels as well as five other independent prognostic factors and divided the patients into three groups with significant prognostic differences (median survival: low-risk [score ≤ 1] 428 days vs. intermediate-risk [score = 2] 102 days vs. high-risk [score ≥ 3] 18 days, P & lt; 0.0001) (Figure 2). The 6-month survival rates were 67%, 46% and 14%, respectively. Conclusions: This study confirmed that the serum B2M level could be an independent prognostic factor in lymphoma-associated HLH and established a prognostic scoring system to predict patients' survival.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2023
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  • 3
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1158-1158
    Abstract: Abstract 1158 Poster Board I-180 Background The importance of theTumor Necrosis Factor (TNF), including TNF-αa and TNF-β, in both the initial preconditioning and effector phases of aGVHD is well established. TNF and TNF receptor II (TNFRII) gene contains multiple single nucleotide polymorphisms (SNPs) in the promoter and transcription start site. There are conflicting datas regarding the cytokines gene polymorphisms and the risk of aGVHD in several studies and no data about Chinese population. This present study was designed to test association of TNFA, TNFB and TNFRII genotype for gene polymorphisms of both donors and recipients with incidence and severity of aGVHD in HLA-matched unrelated allo-HSCT within Chinese population. Methods A total of 138 unrelated donor/recipient pairs, who had undergone HLA-matched allo-HSCT from January 2001 to March 2009 at the First Affiliated Hospital of Zhejiang University School of Medicine, were tested for TNFA (TNFαa-857 C 〉 T,TNFαa-863 C 〉 A,TNFαa-1031 T 〉 C), TNFB (TNFβ+252 A 〉 G) and TNFRII (codon 196 T 〉 G) polymorphism allele frequencies and genotype. SNPs were analyzed by Multiplex Snapshot. Results (1) The TNFαa-857 C/C genotype of the donor or recipient was significantly associated with a higher risk of aGVHD (for donor type:75.7% vs 41.9%, P=0.001; for recipient type: 72.7% vs 50.0%, P=0.039) and a higher incidence of grade II-IV aGVHD( for donor type:50.5% vs 19.4%, P=0.002; for recipient type:48.2% vs 25.0%, P=0.033). (2) The TNFβ+252*G allele of the donor or recipient was significantly associated with a higher incidence of aGVHD (for donor type:74.5% vs 46.9%, P=0.005; for recipient type: 75.0% vs 47.1%, P=0.005); (3) The TNFRII196 T/T genotype of the donor or recipient was significantly associated with a higher incidence of aGVHD (for donor type:73.7% vs 53.8%, P=0.028; for recipient type: 73.3% vs 58.3%, P=0.086); (4) TNF and TNFRII geng polymorphic features, together with other clinical and biological factor (patient's age, donor-recipient gender, diagnosis, conditioning regimen, transplant material and GVHD prophylaxis), were subjected to multivariate analysis for aGVHD manifestation in order to exclude indirect association of gene polymorphic features. In multivariate analysis, donor-recipient gender (female to male) (RR=1.602,95%CI: 1.035-2.479, P=0.034), the TNFαa-857 C/C genotype of donor (RR=2.177, 95%CI: 1.204-3.938, P=0.01) and the TNFβ+252*G allele of recipient (RR=1.920, 95%CI: 1.116-3.304, P=0.018) were found to significantly contribute to the development of aGVHD. The TNFαa-857C/C genotype of donor (RR=3.211, 95%CI: 1.373-7.509, P=0.007) and the TNFβ+252*G allele of recipient (RR=2.174, 95%CI: 1.063-4.443, P=0.033) were also associated with a higher incidence of grade II-IV aGVHD; (5) The genotypes of TNFαa-863 and TNFαa-1031 were not found to be associated with the risk of aGVHD. Conclusions These results, which is the first report of TNF and TNF receptor polymorphic features of Chinese population with the risk of aGVHD, suggest an interaction of the donor and recipient TNFαa-857, TNFβ+252 and TNFRII196 genotypes on risk of aGVHD. These results are helpful for predict allo-HSCT outcome, identify more suitable donors and clarify therapy on an individual patient basis. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 4
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5116-5116
    Abstract: Abstract 5116 Multiple myeloma (MM) is a malignant neoplasm of plasma. The rates of complete remission (CR) or very good partial remission (VGPR) for patients received conventional chemotherapy are still low with median overall survival about 3 years. Here we report our results with combination therapy based on bortezomib in the Chinese population and investigat the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients. Metohds: Between 1st Feb. 2006 and 31st Dec. 2010, 102 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on bortezomib. Sixty-four patients were male and 38 were female. Median age was 59 years (range 31–86 years). Forty-two patients were stage 3 according to the International Staging System, 36 patients were stage 2 and 24 patients were stage 1. The combinations included dexamethasone (BD group ), dexamethasone plus subsequent thalidomide (BDT group ) and dexamethasone plus cyclophosphamide (BDC group ) or epirubicin (BDA group ) based on bortezomib. Thirty-five patients were in BDT group, 19 in BD group, 32 in BDC group and 16 in BDA. All patients received a median of three cycles of therapy (range 1–5 ). The IMWG criteria was used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3. Results: The efficacy of the triplet combination therapy based on bortezomib including BDT, BCD and BAD were better than BD group, with response rate greater than or equal to partial remission(≥PR) 85.7%, 90.6%, 93.7% and 68.4%, respectively. The efficacy of BDA and BDC group were significantly superior to BD group (P=0.048,0.050). Bortezomib in combination with chemotherapy was highly effective as treatment for symptomatic multiple myeloma, even only after one cycle. The efficacy for patients received one cycle of BDT, BD, BCD and BAD was 65.7%, 42.1%, 65.6% and 62.5%, respectively. Patients treated with BD had suboptimal responses to those received BDT, BCD and BAD treatment and one cycle of BCD was superior to one cycle of BD (P=0.019).The median follow-up time was 17m (1–60m), including 31m (1–60m) for 35 patients in BDT group and 16m (2–29m) for the remaining 67 patients. The median progression-free survival (PFS ) of BDT group was 15m (9.8–20.2m ) while BD group was 12m (8.1–15.8m), BCD group was 13m (5.9–20.1m ), and BAD group was 12m (7.8–16.2m ), without significant difference. The median overall survival (OS ) of BDT group was 35m (13.2–56.8m ) while BD, BCD and BAD groups was not reached yet. There was no significant difference in OS among groups, but BCD and BAD were superior to BD group (P=0.104, 0.142 ). The frequent treatment-emergent adverse events includes hematologic adverse events such as neutropenia, anemia, thrombocytopenia and the non-hematologic adverse events like fatigue, infection, constipation, diarrhea, pleural effusion and ascites, herpes zoster and peripheral neuropathy. Patients treated with BDT were more likely to show peripheral neuropathy than those treated with BD, BCD and BAD (91.4% vs 73.6%, 68.7%, 74.9% ), but there is no statistical significant difference (P = 0.131), Grade 2 or 3 peripheral neuropathy was occurred in 45.7% of BDT group significantly higher than BD, BCD and BAD groups. (21.0%, 15.7% and 18.7%, P = 0.028 ). Other related adverse events in all the groups had no significant difference. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment. Conclusions: Our preliminary experience in Chinese patients indicated that combination chemotherapy based on bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC, BDA or BDT regimens may be more superior to BD in Chinese population. There were relative lower rates of DVT/PE in the Chinese patients with MM received combination chemotherapy based on bortezomib. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5455-5455
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5455-5455
    Abstract: Background: Human embryonic stem (hES) cells are distinguished by their capacity for self-renewal and pluripotency. Here we characterize the differentiation of hES cell-derived endothelial cells (hESC-ECs), use molecular imaging techniques to examine their survival and function in vivo. Methods and Results: Here we introduced two-step procedures to increase endothelial differentiation efficiency of hESCs by subcultured embryoid bodies (EBs) in collagen. Single cell suspensions from EBs sprouting in collagen were obtained by treatment with collagenase and Liberase Blendzyme IV and CD31/CD144 positive cells were isolated by FACScan. After isolation, these hESC-ECs express endothelial cell markers similar to HUVEC, form vascular-like channels, and incorporate DiI-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) in vitro. Real time PCR array described increasing endothelial transcription. Using whole genome microarrays, we investigated the hESCs derived endothelial cells (hESC-ECs) transcriptome that occur among sequenced hESCs differentiation processes and human umbilical vein endothelial cells (HUVECs). We found that hESC-ECs expressed endothelial gene at pattern similar to HUVECs. By intravital microscope, we demonstrated that hESC-ECs can form function vessels with blood flow. Conclusion: Taken together, two-steps procedures increased the endothelial differentiation efficiency hESCs, and hESC-ECs can form functional vessel in vivo.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 6
    Online Resource
    Online Resource
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 4620-4620
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 4620-4620
    Abstract: Objective:To evaluate the clinical outcome of granulocyte colony-stimulating factor (G-CSF) priming regimen in treatment of refractory, relapsing and senile aute myeloid leukemia. Materials and Methods:16 patients, 10 men and 6 women ranged in age from 15 to 78 years (median 48), with refractory, relapsing or senile acute myeloid leukemia were treated in our hospital between March 2002 and January 2004. All patients were diagnosed with MIC (morphologic, immunologic, cytogenetic) classification. The control group consists of 18 patients (12 men and 6 women, median age 48) with refractory, relapsing or senile acute myeloid leukemia treated in our hospital between 1999 and 2002. All of them were also diagnosed with MIC. All patients enrolled were treated with G-CSF-priming regimen consisting of low-dose cytosine arabinoside (Ara-C 10mg.m−2.12h−1, subcutaneously,day1–14), aclarubicin (Acla5-7mg.m−2.d−1, continuous intravenous infusion, day 1–8; or 10–14mg.m−2.d−1, continuous intravenous infusion, day1–4) or homoharringtonine (HHT 1mg.m−2.d−1, continuous intravenous infusion, day1–14), and concurrent use of G-CSF (100ug.m−2.12h−1, subcutaneously, day 1–14). In the course of chemotherapy, blood routine examinations were made every other day, and G-CSF was suspended while WBC 〉 20x109/L. Chemotherapy intermission was 14–21 days. If two courses were of no effect, then the investigation was terminated. Patients in the control group received intensive chemotherapy with medium /high dosed Ara-C (1-3g.m−2.12h−1× 3–5d), combined with mitoxantrone or daunorubicin (DNR) or etoposide (vp-16).Statistics:Enumeration data was analyzed by Chi-square test. Results: All patients accomplished the chemotherapy, with no treatment related death. 9 of the 16 patients achieved complete remission. The CR rate was 56.25%, compared with 22.2% of the control group (Χ2=4.15, P 〈 0.05). However, the total effective rate (68.75%) was not statistically higher than the control group (44.4%) (Χ2=2.03, P 〉 0.05). Therapy related mortality (0.0%) was apparently decreased in priming group than in control group (38.9%) (Χ2=7.84, P 〈 0.01). Conclusions:Our study shows that the priming regimen is effective and safe to refractory, relapsing, secondary or senile acute myeloid leukemia. Further studies are necessary to evaluate the long-term effects of this new therapeutic regimen in AML.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    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. 116, No. 21 ( 2010-11-19), p. 1303-1303
    Abstract: Abstract 1303 Background: Leukemia relapse arising in cells of donor origin in the transplant recipient, called donor cell leukemia (DCL), is a rare disease entity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The precise etiological mechanisms of DCL are unravelled and almost all the reported cases do not suggest a common mechanism. Careful analyses of the mechanisms with respect to the oncogenic transformation of donor-derived cells might provide a valuable insight into understanding of leukemogenesis.We aimed to assess whether those genetic mutations implicated in the development of common forms of AML contribute to the “leukemization” of donor cells in DCL. Methods: (1) A 36-year-old male was diagnosed with AML-M4. Cytogenetic evaluation demonstrated an abnormal clone 46 XY, del (9) (q11 q34) in 10/10 cells. The patient underwent `allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from a HLA-identical sister. Short tandem repeats (STR) analyses on day +28 showed complete donor chimera. Thirteen months after SCT, bone marrow aspiration revealed leukemia relapse. STR analyses showed still absolute donor chimera. The karyotype of bone marrow cells of the patient showed a new clonal chromosome abnormality: 45,XX, der(15;22) (q10;q10) in 10/10 cells, which was completely identical to the karyotype of the donor. Molecular evaluation suggested the patient developed DCL from a HLA-identical sibling. The examination of the donor's bone marrow showed normal and no malignant clone was detected by flow cytometry and fluorescence in-situ hybridization analyses. The donor remains healthy during a 25-month follow-up. (2) A series of archival stained bone marrow slides of the patient, including at the times of diagnosis, CR after one course of induction chemotherapy, lasting CR, before SCT, 1 month, 9 months and 12 months after SCT, samples of mononuclear-cell-enriched bone marrow at the times of relapse and CR after relapse, and buccal mucosal swab specimen during remission were available. (3) Buccal mucosal swab specimen and samples of mononuclear-cell-enriched peripheral blood and bone marrow were available from the donor. (4) Genomic DNA was extracted and analyzed for mutations in fms-related tyrosine kinase 3 gene (FLT3), neuroblastoma RAS viral oncogene homolog gene (NRAS), the CCAAT enhancer-binding proteinα gene (CEBPA), myeloid-lymphoid or mixed-lineage leukemia gene (MLL), and nucleophosmin gene (NPM1). Results: (1) DNA obtained from the patient during diagnosis was found to exhibit three different mutations in CEBPA, the gene encoding the crucial granulocytic differentiation factor C/EBPα. The mutation1 was the duplication of a cytosine residue at nucleotide 247 (247dupC) which resulted in the corresponding protein terminating prematurely at codon106 (Gln83fsX106). The mutation2 was a 6-bp duplication comprised nucleotides 584 to 589 (584—589dup) which resulted in an internal tandem duplication of amino acids 195 to 196 (His195—Pro196dup) in the protein. The mutation3 was a 3-bp duplication comprised nucleotides 914 to 916 (914—916dup) which resulted in the duplication of amino acids 305 (Gln305dup) in the protein. The 584—589dup mutation was remain found in DNA from the patient during lasting remission before SCT and from his buccal swab specimen, indicating this mutation should be germ-line mutation. In contrast, other two mutations were not found in the patient during remission and buccal swab specimen, indicating these two mutations should be somatically acquired. (2) The 584—589dup germ-line mutation was also found in DNA from peripheral blood cells, bone marrow cells and buccal swab specimen from the donor. (3) Donor-derived cells in the patient at the times of 1 month, 9 months and 12 months after SCT only exhibited the single germ-line mutation. When the patient relapsed with DCL, donor-derived leukemic cells were found to develop two somatic mutations in CEBPA in the patient microenvironment, which were completely identical to those observed in the patient with de novo leukemia. No other mutations were identified in FLT3, NRAS, MLL and NPM1 genes. Conclusions: Our findings suggest that multiple mutations of CEPBA impairing C/EBPα function may be sufficient to induce AML and a single mutation of CEBPA is not leukemogenic, but is the first step and predisposed to development of other mutations, ultimately inducing AML. 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: 2010
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  • 8
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1159-1159
    Abstract: Abstract 1159 Poster Board I-181 Background In allogeneic SCT, genetic factors such as donor and recipient gene polymorphisms of pro- and anti-inflammatory cytokines have been associated with the incidence and severity of GVHD. However, the influence of such donor and recipient gene polymorphisms on other outcomes, such as early infection after SCT, has seldom been described. TNFαa, TNF receptorII (TNFRII), IL-10 and TGF gene contain multiple single nucleotide polymorphisms (SNPs) in the promoter and codon region. We thus studied the association of this panel of candidate gene polymorphisms with the incidence of the first episodes of early bacterial infections within 100 days after allo-HSCT. Methods A total of 138 unrelated donor/recipient pairs, who had undergone HLA-matched allo-HSCT from January 2001 to March 2009 at the First Affiliated Hospital of Zhejiang University School of Medicine, were tested for TNFαa(TNFαa-857 C 〉 T, TNFαa-863 C 〉 A, TNFαa-1031 T 〉 C), TNFRII (codon196 T 〉 G), IL-10 (IL10-1082 A 〉 G, IL10-819 T 〉 C, IL10-592 A 〉 C), TGF (TGF-509 T 〉 C, TGF+869 C 〉 T) polymorphism allele frequencies and genotype. SNPs were analysed by Multiplex SnaPshot. We considered the first episodes of early bacterial infections within 100 days after allo-HSCT have developed when sepsis, pneumonia, or septic shock was diagnosed according to previously published criteria. Results (1) 133 patients achieved complete donor chimerism in the peripheral blood and 5 patients had graft failure. All patients achieved an absolute neutrophil count (ANC) greater than 0.5×109/L at day 13 (7∼22) and platelet recovery at day 15 (7∼64). The cumulative incidence of at least one bacterial infection was 47.8% (pneumonia and intestinal infection are the most popular) within 100 days after allo-HSCT. There is no significant difference in the time to neutrophil recovery in patients who experienced early bacterial infections with those who did not (13.6 vs 12.8,P=0.115). (2) The TNFαa-857 C/C genotype and TNFRII 196 T/T genotype of the donor were significantly associated with a higher risk of early bacterial infection ( for TNFαa-857 C/C genotype: 53.3% vs 29.0%, P=0.024 ; TNFRII 196 T/T genotype: 53.5% vs 33.3%, P=0.038); (3) The TGF-509 T/T genotype of the donor was significantly associated with a higher risk of early bacterial infection (62.5% vs 41.8, P=0.038); (4) Transplantation from donors with IL10-819 C/C genotype or IL10-592 C/C genotype were significantly associated with a higher risk of early bacterial infection (for IL10-819 C/C genotype: 71.4.1% vs 45.3%, P=0.034; IL10-592 C/C genotype: 70.0.1% vs 45.8%, P=0.055); (5) The genotypes of TNFαa-863, TNFαa-1031, IL10-1082 and TGF+869 were not found to be associated with the risk of early bacterial infection. Conclusions Recent studies have shown that the generation potential of IL-10 is influenced by the polymorphism of the IL-10 gene. The IL10-819*C allele and IL10-592 *C allele are associated with higher secretion of IL-10 than IL10-819*T allele and IL10-592*A allele. In our data, a higher risk of early bacterial infection with IL10-819 C/C and IL10-592 C/C genotype was postulated to be associated with a higher IL-10 production, which suppressed reactive T-cell response. These results, which is the first report of TNFαa, TNFRII, IL-10and TGF polymorphic features of Chinese population with the risk of early bacterial infection after HLA-matched unrelated allo-HSCT, suggest an interaction of the donor TNFαa-857C/C, TNFRII 196 T/T, IL10-819 C/C, IL10-592 C/C and TGF-509 T/T genotypes on risk of early infection. These results are helpful for predict allo-HSCT outcome, identify more suitable donors and clarify therapy on an individual patient basis. 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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  • 9
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 5048-5048
    Abstract: Abstract 5048 Introduction: Novel drugs, such as bortezomib, have significantly improved the response rates in multiple myeloma (MM), but little has been reported on bortezomib-based therapies in Chinese patients. Methods: In the initial eight 28-day cycles, newly diagnosed ymptomatic patients were treated with combination therapy including bortezomib plus dexamethasone (PD) and the triplet combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), thalidomide (PDT) between February 1, 2006 and May 31, 2012. Among the above regimens, bortezomib (1. 3 mg/m2) was given intravenously on days 1, 4, 8, 11, while dexamethasone (20 mg/m2/day) was given intravenously on days 1–2, 4–5, 8–9, 11–12, adriamycin (10 mg/m2) was given intravenously on days 1–4, cyclophosphamide (200 mg/m2) was given intravenously on days 1–4 and thalidomide (100 mg) was administered orally each day. Results: The overall response rate (¡Ý partial response, PR) of all the 151 eligible patients was 88. 7% (including 29. 8% very good partial response (VGPR) and 25. 8% complete response/near complete response (CR/nCR). The responses per IMWG criteria for patients are shown in Table 2. The median PFS was 20. 3 months (95% CI: 14. 8–25. 8 months) in the patients who received PDT, 24. 8 months (95% CI: 20. 0–30. 0 months) in the patients who received PCD, 22. 9 months (95% CI: 17. 6–28. 2 months) in patients who received PAD and 21. 8 months (95% CI: 15. 3–28. 3 months) in the patients who received PD with no significant differences between the groups. The median OS for PD arm was 42. 0(95% CI: 20. 1–63. 9 months) months while other arms were not reached, but the median OS for PDT, PCD and PAD was significant longer than PD (P=0. 042, 0. 039, 0. 010). PFS and OS for patients with favorable cytogenetics were significantly longer than those with unfavorable cytogenetics by FISH. The frequently observed hematologic toxicities (Grade 3/4) were: thrombocytopenia (17. 00%), neutropenia (15. 00%) and anemia (8. 61%). The most common non-hematologic toxicities included (all Grades) peripheral neuropathy(57. 61%), fatigue(27. 15%), infection(23. 84%), constipation(22. 52%), herpes zoster(17. 22%) and diarrhea(15. 23%). Conclusions: Our experience indicated that bortezomib-based regimens were active and well-tolerated for MM patients, and triplet combinations were superior to PD. Serious Adverse events were rare in the Chinese patients with MM who received bortezomib-based chemotherapy. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    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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  • 10
    In: Blood, American Society of Hematology, Vol. 142, No. Supplement 1 ( 2023-11-02), p. 6261-6261
    Abstract: Introduction Stage I diffuse large B-cell lymphoma (DLBCL) is defined as the involvement of a single lymph node or a group of adjacent nodes, or the presence of isolated extranodal lesions without nodal involvement. Generally, the prognosis of stage I DLBCL is excellent with 5-year overall survival (OS) over 90%. However, differences in disease characteristics and prognosis between elderly and younger patients with stage I DLBCL were not clear. Methods In this study, we conducted a retrospective data collection from 255 newly diagnosed patients with stage I DLBCL who were above 60 years old. The data was collected from 19 medical centers of of Jiangsu Cooperative Lymphoma Group (JCLG) located in Jiangsu Province, China. To enroll, patients had to undergo staging using either positron emission tomography/computed tomography (PET/CT) or contrast-enhanced CT scans of the chest, abdomen, and pelvis (C/A/P CT) with contrast, as well as bone marrow examination. Results The clinical characteristics of the 255 patients are presented in Table 1. The median age at presentation was 69 years, with a range of 61 to 92 years old. Among the 255 patients, 65.9% had at least one coexistent disease. A high Charlson Comorbidity Index (CCI), defined as ≥2, was found in 10.1% of patients. 63.9% had extranodal disease. The most common sites of extranodal involvement were the stomach (37.4%), intestine (19.0%), testes (11%), breast (7.4%), skin/soft tissue (5.5%), and sinus/nose (5.5%). According to the Hans algorithm, the non-GCB subtype accounted for 63.7% of patients and did not show a significant difference between the nodal and extranodal groups. None of the patients were diagnosed with double-hit lymphoma. Additionally, EBER was found to be positive in 3.7% of patients (5/134). The treatment approaches are outlined in Table 1. A total of 84.5% patients received the R-CHOP regimen as their primary treatment. The median number of R-CHOP courses administered was 6. Among the 204 patients with treatment evaluation records, 183 (89.7%) achieved complete remission (CR). With a median follow-up time of 30 months, 32 patients died during the follow-up period. Among them, 18 died from causes unrelated to lymphoma at a median age of 73 years. The 3-year progression-free survival (PFS) rate was 81.5% and the 3-year OS rate was 85.6%. In the univariate analysis, age ≥75 years (HR 3.30, P & lt; 0·001) and CCI ≥2 (HR 2.92, P = 0·002) were significantly associated with worse PFS; age ≥75 years (HR 3·29, P = 0·001), CCI ≥2 (HR 2.57, P = 0·022) and non-GCB subtype (HR 1.79, P = 0·018) were significantly associated with worse OS. In multivariate analysis, age ≥75 years (HR 2.91, P = 0·001) and CCI ≥2 (HR 2.32, P = 0·02) remained independent risk indicators for worse PFS; age ≥75 years (HR 2.57, P = 0·015) and non-GCB subtype (HR 1.74, P = 0·025) were independent risk indicators for worse OS. None of the prognostic models including IPI, NCCN-IPI or stage-modified International Prognostic Index (sm-IPI) demonstrated statistical significance. However, by incorporating age≥75 and CCI≥2 into the sm-IPI, we could be able to provide a more accurate prediction of the prognosis for elderly patients with stage I DLBCL (Figure 1). Relapse occurred in 20 patients at a median time of 9 months. 91.7% (11/12) of patients with early relapse (defined as PFS less than 24 months) experienced recurrence in the same anatomical site as the primary disease. In contrast, only 25% (2/8) of patients with late relapse exhibited relapse in the initial site. Conclusion To the best of our knowledge, this is the largest retrospective study conducted specifically on stage I DLBCL in the Asian population during the rituximab era. Our findings suggest that elderly patients with stage I DLBCL have a higher non-lymphoma-related mortality rate and a higher likelihood of relapse in the same anatomical site for early relapses compared to late relapses. Integrating age ≥75 and CCI score into the sm-IPI will help to better assess prognosis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    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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