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  • Jiang, Xuejie  (6)
  • Xu, Dan  (6)
  • 2015-2019  (6)
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  • 2015-2019  (6)
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Subjects(RVK)
  • 1
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5170-5170
    Abstract: AML1/ETO-positive acute myeloid leukemia (AML) is a heterogeneous malignancy. Up until now, the difference between adult ( 〉 14-year old) and pediatric (≤14-year old) AML1/ETO+ AML remains unclear. In this retrospective multi-center study we analyzed 173 AML1/ETO+ AML patients including 98 adults and 75 kids, and found that AML-M2 phenotype was the most common morphology, especially higher in adult patients with an incidence of 92.9%, as compared with 82.7% (P=0.005) in pediatric patients. Furthermore, higher incidence of extramedulary leukemia (29.6% vs. 13.3%, P=0.001) and C-KIT mutation (21/67, 31.3% vs. 12/66, 18.2%, P=0.079) were observed in adult patients than pediatric patients. No significant difference in gender ratio, peripheral white blood cells count, immunology and cytogenetic abnormality including affiliated cytogenetic abnormalities and lose of sex chromosmoe between the two age groups. Among adult patients, idarubicin combined with cytarabine (IA) or daunorubicin combined with cytarabine (DA) was the major induction regimens, while FLAG (fludalabin,cytarabine and G-CSF) combined with idarubicin or DA combined with etoposid (DAE) was the main regimens in pediatric patients for one to two cycles. Not only the first-cycle complete remission (CR) rate (69/74, 93.2% vs. 56/95, 58.9%, P 〈 0.001), but also the second-course cumulative CR rate (73/74, 98.6% vs. 82/95, 86.3%, P=0.004) in pediatric patients was much better than that in adult patients. After obtaining CR, standard dose cytarabine (SDAC)-based or medium dose cytarabine (MDAC)-based regimens were given to the adult patients as the major consolidation regimens, while pediatric patients received MDAC or homoharringtonine combined with cytarabine and etoposid (HAE). With a median of 23.5(2-126) months follow-up, cumulatively 35/87(40.2%) patients relapsed and 39/98(39.8%) cases died in adult group, which were much higher than that in pediatric patients, with the cumulative incidence of recurrence of 18/74(24.3%) (P=0.032) and cumulative death rate of 13/75(17.3%) (P=0.001). Survival analysis showed that EML [RFS: HR 3.20(1.63-6.28), P=0.001; OS: HR 2.92(1.55-5.51), P=0.001] and C-KIT mutation [RFS: HR 3.17(1.47-6.93), P=0.003; OS: HR 2.24(1.03-4.86), P=0.041] were the adverse factors for relapse free survival (RFS) and overall survival (OS). Nevertheless, neither these two factor were negative for the survival of pediatric patients. Taking together, significant difference in bone marrow morphology, incidence of EML and C-KIT mutation, also prognostic factors were observed between the adult and pediatric AML1/ETO+ AML patients. Intensive induction might be a main reason for higher CR rate and better survival in pediatric 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: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 2
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5245-5245
    Abstract: BACKGROUND : Mutations of internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) contributed to poor prognosis in cytogenetically normal acute myeloid leukemia (CN-AML). FLT3 tyrosine kinase inhibitor sorafenib in combination with chemotherapy was applied to treat FLT3-ITD AML patients with limited efficacy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was considered as a potent therapeutic regimen in FLT3-ITD patients, but additional sorafenib maintenance was indispensable to support their long-term survival after allo-HSCT. Studies showed that increasing ITD size may be accompanied with decreasing OS and RFS in AML patients, but it remained controversial about the prognostic implication of ITD mutant lengths, the prognostic influence was important to evaluate in determining the therapeutic strategy for AML patients with different ITD lengths. METHODS: Total 185 CN-AML patients with and without FLT3-ITD mutations were enrolled in this study. We retrospectively studied the clinical characteristic, treatment response, survival and relapse risk after chemotherapy or allo-HSCT plus sorafenib in these patients. Distribution of ITD lengths detected in AML patients suggested two groups including long (≥70bp) and short ITD length ( 〈 70bp). Influence of FLT3-ITD mutation and its length were investigated after chemotherapy or allo-HSCT plus sorafenib. RESULT: FLT3-ITD mutations were detected in 15 percentage of AML patients, and associated with leukocytosis, high blast percentage in bone morrow (BM) and increased risk of treatment failure. FLT3-ITD mutations indicated decreased complete remission (CR) rate, overall survival (OS) and relapse-free survival (RFS), and increased relapse risk (RR) in AML patients after chemotherapy plus sorafenib. Patients with long ITD length (≥70bp) had worse OS and RFS, and more relapse probability than these with short ITD length ( 〈 0bp) or FLT3-WT, but patients with short ITD length and FLT3-WT had the similar RFS and RR after chemotherapy. Allo-HSCT plus sorafenib maintenance significantly prolonged OS and RFS, decreased RR in FLT3-ITD patients, especially in these with long ITD length instead of those with short ITD length. CONCLUSION: Our findings indicated that FLT3-ITD mutation and long ITD length had negative effect on treatment response and prognosis in CN-AML patients. Allo-HSCT plus sorafenib maintenance was an effective strategy to improve survival and decrease relapse probability, abrogated disadvantage from long ITD length in FLT3-ITD 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: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 3
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4932-4932
    Abstract: Introduction. Most acute myeloid leukemia (AML) patients with adverse prognosis either fail to achieve complete remission (CR) or relapse after short-term remission, new strategies are needed to improve therapeutic effect in these patients. Gene silencing via DNA methylation are frequent and reversible in high-risk AML, it provides the possibility to treat AML patients with DNA-hypomethylating agent. Decitabine alone has limited anti-leukemia effect and minimal toxicity. Studies demonstrated that decitabine prior to chemotherapy was likely to increase efficacy in AML. In this study, we investigated the effect of decitabine on susceptibility to cytotoxic drugs in chemoresistant AML cells. Efficacy and safety of decitabine prior to HAA regimen was evaluated in refractory, relapsed and high-risk AML patients. Methods. HL60, HL60/ADR, Kasumi-1, and primary AML cells were pre-treated with 1.0 μM decitabine for 72 hours, Sensitivities to harringtonine, adriamycin, cytarabine and the combination was determined by MTT, apoptosis was analyzed by flow cytometry. Protein expression was detected by western blotting. In clinic, Twenty-three patients were enrolled in decitabine prior to HAA regimen, and twenty-four patients in HAA alone. CR ratio was used to evaluate efficacy. Durations of neutrocytopenia or thrombcytopemia and infection incidence were observed to assess the safety. All of patients were followed up to 36 monthes, overall survival (OS) and disease-free survival (DFS) were calculated. Result. Decitabine increased sensitivity and apoptosis induced by harringtonine in HL60/ADR, as well as adriamycin and cytarabine in HL60/ADR and Kasumi-1 cells. But no change in sensitivity to each drug was observed in HL60, and sensitivity to harringtonine in Kasumi-1. The similar changes in sensitivity to adriamycin and cytarabine were also observed in primary AML cells from refractory patients (n=6). Cytotoxic effect of HAA was alsoincreaed by decitabine in HL60/ADR and Kasumi-1 cells (p=0.004, 0.018). Western blotting showed that decitabine decreased expression of DNMT1, activation of p53 and inhibition of c-Myc, Survivin and Bcl-2. In clinic, 16 (69.6%) patients in decitabine plus HAA regimen responded to the first course of induction therapy: 14 CR (60.9%) and 2 PR (8.7%). 1 in 2 patients with PR achieved CR after second course induction. It brought the overall CR was 65.2%. Otherwise, 10 (45.8%) patients in HAA regimen alone responded to the first induction: 7 CR (29.2%) and 4 PR (16.7%), 3 in 4 patients with PR achieved CR after the second induction, and overall CR reached 41.7%. The first-cycle CR ratio in decitabine plus HAA was higher than that in HAA alone (p=0.041). Patients continued to receive chemotherapy alternatively combined with decitabine. The median OS was 14 months in chemotherapy plus decitabine, 6 months in chemotherapy alone, and median DFS were 18 and 5 months in the former and latter. No significant difference was observed in the time of neutrophil (p=0.832, 0.631) or platelet recovery (p=0.798, 0.544) after induction and intensification therapy. The incidences of infection were also similar (p=0.724, 0.697). The clinic data indicated that decitabine plus HAA regimenit was efficacy and well-tolerated to treat refractory AML patients. Conclusion. Our results demonstrated that decitabine increased cytotoxic effect against chemoresistant AML cells. Combination of decitabine and HAA was safe and efficacy to treat refractory/relapsed AML. These findings support clinic protocols based on decitabine prior to chemotherapy to overcome resistance and improve therapeutic efficacy in AML patients. Disclosures Carter: PrismBiolab: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 4
    In: Oncology Letters, Spandidos Publications, ( 2017-11-13)
    Type of Medium: Online Resource
    ISSN: 1792-1074 , 1792-1082
    Language: Unknown
    Publisher: Spandidos Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2573196-8
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  • 5
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5249-5249
    Abstract: Gene mutations play a critical role in leukemogenesis of AML1-ETO-positive acute myeloid leukemia (AE-AML). Nevertheless, gene mutation profile in this subtype leukemia remains unclear, and their clinical effect might be underestimated. In this study, we detested gene mutations at diagnosis and relapse with next-generation sequencing in 64 newly diagnosed AE-AML patients, and verified the results with Sanger sequencing at the same time. Our results showed that 68.8% patients presented recurrent mutations at diagnosis and 6/11 cases underwent genetic alterations at relapse. C-KIT mutation was the most common event at diagnosis, with an incidence of 42.2%, followed by ASXL1 (15.6%), MET (12.5%), MLH1 (9.4%) , TET2 (7.8%), and FBXW7, TP53 and DNMT3A (7.8%), etc. Also, C-KIT mutation was the most common molecular event associated with relapse (7/11, 63.6%). No significant difference in the clinical characteristic between the gene mutation and wild type (WT) groups was observed, except of higher incidence of additional cytogenetic abnormalities (ACAs) (P=0.025) in TP53 mutation patients. C-KIT (exon 8, 17) mutation but not exon 10 adversely affected on survival. Also ASXL1 and TP53 mutation were poor for the RFS (P 〈 0.05), and ASXL1, MET, FBXW7 and TP53 mutation negatively impacted on the OS (P 〈 0.05). Multivariate analysis showed C-KIT (exon 8, 17) and ASXL1 mutations were the independent adverse factors for survival. Further, co-mutation of these two genes showed even worse effect on survival. Taking together, additional gene mutations are critical in the development and progression of AE-AML. C-KIT and ASXL1 mutations are the two most common molecular events in this subtype leukemia. Single mutation of C-KIT (exon 8, 17) or ASXL1 poorly affects on survival, even worse in the co-mutation. Figure. Figure. 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: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 6
    In: Oncology Reports, Spandidos Publications, ( 2019-10-15)
    Type of Medium: Online Resource
    ISSN: 1021-335X , 1791-2431
    Language: Unknown
    Publisher: Spandidos Publications
    Publication Date: 2019
    detail.hit.zdb_id: 1222484-4
    detail.hit.zdb_id: 2120548-6
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