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  • 1
    In: Blood, American Society of Hematology, Vol. 121, No. 20 ( 2013-05-16), p. 4056-4062
    Abstract: Risk stratification treatment of t(8;21) acute myeloid leukemia may decrease relapse and improve long-term survival. Allo-HSCT benefited high-risk patients, but impaired the survival of low-risk patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 162-162
    Abstract: Abstract 162 Background and Aims. The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) in the first chronic phase (CP) in the imatinib era have not previously been evaluated. This prospective cohort study was designed to compare the medical outcomes and quality of life (QOL), with imatinib versus allo-HSCT from an HLA-matched sibling donor for CML in the first CP including the early CP (ECP; a CML duration 〈 12 months) and the late CP (LCP; a CML duration ' 12 months). Patients and methods. From April 2001 to April 2010, patients treated consecutively at the Peking University People's Hospital, Peking University Institute of Hematology were nonrandomly assigned to treatment with imatinib or allo-HSCT according to whether the patient had an HLA-matched sibling donor; those with an HLA-identical sibling donor were assigned to the allo-HSCT group, and the others were assigned to the imatinib group. QOL of surviving patients still in the imatinib and allo-HSCT groups was measured by the Medical Outcomes Survey Short Form 36 (MOS SF-36) at the end of the study evaluation period in April 2011. Results. In total, 463 patients were recruited, 209 patients were assigned to the allo-HSCT group and 254 patients were assigned to the imatinib group, respectively.Based on a ten-year follow-up period, a multivariate analysis revealed that allo-HSCT was an independent adverse prognostic factor for event-free survival (EFS; estimated HR=2.4, P=0.002 and estimated HR=0.31, P 〈 0.001) and overall survival (OS; estimated HR=6.9, P 〈 0.001 and estimated HR=26.2, P=0.001) for the total population (n=463) and the patients in the ECP (n=348), and an independent favorable predictor of progression-free survival (PFS; estimated HR=3.2, P=0.020) for the total population. Imatinib was superior to allo-HSCT, with six-year EFS and OS rates of 83.6% vs. 76.6% (P=0.041) and 96.4% vs. 82.0% (P 〈 0.001), respectively, for the entire cohort and 90.3% vs. 74.3% (P=0.001) and 99.4% vs. 80.2% (P 〈 0.001), respectively, for the patients in the ECP, despite six-year PFS rates of 90.7% vs. 96.6% (P=0.014), respectively, for the entire cohort and 95.9% vs. 97.3% (P=0.303) respectively, for the patients in the ECP. Both treatments resulted in similar EFS and OS rates in those in the LCP (n=115), with a probability of six-year EFS rate of approximately 80% and six-year OS rate of more than 90%. More LCP patients in the imatinib group experienced relapse compared with those in the allo-HSCT group, with six-year PFS rates of 86.0% vs. 100% (P=0.035), respectively. There was no correlation between the EBMT risk score and EFS, OS or PFS in the patients receiving allo-HSCT. Among the 392 surviving patients who were invited to participate in the QOL survey, 295 (75.3%) patients including 180 of 218 (82.6%) in the imatinib group and 115 of 174 (66.1%) in the allo-HSCT group, respectively, completed the questionnaires. A multivariate analysis revealed that there was no correlation between the treatment mode and the physical health for the total, ECP and LCP population, however, allo-HSCT was one of the independent factors associated with good mental health (estimated HR=0.5, P 〈 0.001) in the ECP patients. The Physical Component Summary were comparable between the imatinib group and the allo-HSCT group, however, the Mental Component Summary of the patients experienced allo-HSCT were better than those receiving imatinib for the total (P=0.001), ECP (P=0.015) and LCP (P=0.010) population. Conclusions. We concluded that imatinib confers significant survival advantages and a desirable QOL and is superior to allo-HSCT as the first-line therapy for patients with CML in the ECP. All trials were registered with www.chictr.org as CHiCHTR-TNC-10000955. Disclosure: No relevant conflicts of interest to declare. 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: 2011
    detail.hit.zdb_id: 1468538-3
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  • 3
    In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 98, No. 11 ( 2019-11), p. 2551-2559
    Type of Medium: Online Resource
    ISSN: 0939-5555 , 1432-0584
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 1458429-3
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  • 4
    In: International Journal of Laboratory Hematology, Wiley, Vol. 44, No. 5 ( 2022-10), p. 892-899
    Abstract: Adult acute myeloid leukaemia (AML) patients with complex karyotype (CK) generally have unfavourable outcomes. CK commonly co‐exists with characteristic chromosomal and genetic abnormalities such as monosomal karyotype (MK), −17 or 17p‐ [abn(17p)] and TP53 mutations. Their individual prognostic significance needs to be clarified. Methods Seventy‐three adult CK‐AML patients and eleven adult non‐CK‐AML patients with TP53 mutations (non‐CK/TP53 mu ) who were diagnosed and received therapy at our institute were enrolled. One hundred and fifty‐seven AML cases retrieved from the cancer genome atlas (TCGA) for validation. Results Among CK‐AML patients, those with TP53 mutations (CK/TP53 mu ) had significantly lower rates of 1‐course induction complete remission (CR), 2‐year relapse‐free survival (RFS) and 2‐year overall survival (OS) than those without TP53 mutations (CK/TP53 wt ); whereas, abn(17p) did not have the above impacts; MK was significantly associated with a lower 2‐year OS rate but was not related to the rates of CR and RFS. Multivariate analysis showed that it were TP53 mutations and treating with chemotherapy alone but not MK and abn(17p) that independently predicted the adverse prognosis for RFS and OS in CK‐AML. Furthermore, non‐CK/TP53 mu patients showed similar rates of CR, RFS and OS to CK/TP53 mu patients. Validation using the TCGA cohort showed that CK/TP53 mu patients had a significantly lower 2‐year OS rate than CK/TP53 wt patients, whereas abn(17p) and MK did not impact OS; the 2‐year OS rate of patients with CK/TP53 wt was similar to that of patients with intermediate‐risk cytogenetics. Conclusion Adult CK‐AML patients have varied risks and TP53 mutations seem to be an independent adverse prognostic factor.
    Type of Medium: Online Resource
    ISSN: 1751-5521 , 1751-553X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 5
    In: British Journal of Haematology, Wiley, Vol. 185, No. 5 ( 2019-06), p. 836-851
    Abstract: Refinement of risk stratification in Philadelphia chromosome (Ph)‐negative B‐cell acute lymphoblastic leukaemia ( ALL ) might aid the identification of patients who are likely to relapse. Abnormal S100 calcium binding protein A16 ( S100A16 ) has been implicated in various cancers, but its function remains unclear. We found S100A16 transcript levels were higher in 130 adults with newly‐diagnosed Ph‐negative B‐cell ALL compared with 33 healthy controls. In 115 of 130 patients who achieved first complete remission, those with high S100A16 transcript levels displayed a lower 3‐year cumulative incidence of relapse ( CIR ; 34% [21, 47%] vs. 40% [48, 72%] ; P  =   0·012) and higher 3‐year relapse‐free survival ( RFS ; 65% [53, 78%] vs. 35% [23, 46%] ; P  =   0·012), especially when receiving chemotherapy only. In multivariate analysis a low S100A16 transcript level was independently‐associated with a higher CIR (Hazard ratio [ HR ] = 3·74 [1·01–13·82] ; P  =   0·048) and inferior RFS ( HR  = 5·78 [1·91, 17·84]; P  〈   0·001). Function analysis indicated that knockdown of S100A16 promoted proliferation and anti‐apoptosis and reduced chemosensitivity. S100A16 over‐expression revealed an opposite trend, especially in a xeno‐transplant mouse model. Western blotting analysis showed upregulation of PI 3K/ AKT and ERK 1/2 in S100A16 ‐knockdown and S100A16 ‐overexpression B‐cell ALL cell lines respectively. Inhibition assays suggested these two signalling pathways participated in the S100A16 ‐mediated proliferation and survival effects in B‐cell ALL cell lines. Trial Registration: Registered in the Chinese Clinical Trial Registry [Chi CTR ‐ OCH ‐10000940]; http://www.chictr.org.cn .
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1475751-5
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  • 6
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 58, No. 6 ( 2017-06-03), p. 1384-1393
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2030637-4
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  • 7
    In: Chinese Journal of Cancer, Springer Science and Business Media LLC, Vol. 35, No. 1 ( 2016-12)
    Type of Medium: Online Resource
    ISSN: 1944-446X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2439836-6
    detail.hit.zdb_id: 2922913-3
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  • 8
    In: Blood, American Society of Hematology, Vol. 117, No. 11 ( 2011-03-17), p. 3032-3040
    Abstract: The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and imatinib for chronic myelogenous leukemia in the accelerated phase (AP-CML) have not previously been evaluated. This cohort study was designed to compare the outcomes of imatinib (n = 87) versus allo-HSCT (n = 45) for AP-CML. A multivariate analysis of the total population revealed that a CML duration ≥ 12 months, hemoglobin 〈 100 g/L, and peripheral blood blasts ≥ 5% were independent adverse prognostic factors for both overall survival (OS) and progression-free survival (PFS). Both treatments resulted in similar survival in low-risk (no factor) patients, with 6-year event-free survival (EFS), OS, and PFS rates of more than 80.0%. Intermediate-risk (any factor) patients showed no difference in EFS and OS, but 6-year PFS rates were 55.7% versus 92.9% (P = .047) with imatinib versus allo-HSCT, respectively. Among high-risk (at least 2 factors) patients, imatinib was by far inferior to allo-HSCT, with 5-year EFS, OS, and PFS rates of 9.3% versus 66.7% (P = .034), 17.7% versus 100% (P = .008), and 18.8% versus 100% (P = .006), respectively. We conclude that allo-HSCT confers significant survival advantages for high- and intermediate-risk patients with AP-CML compared with imatinib treatment; however, the outcomes of the 2 therapies are equally good in low-risk patients. All trials were registered with the Chinese Clinical Trial Registry (www.chictr.org) as CHiCTR-TNC-10000955.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    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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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4270-4270
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4270-4270
    Abstract: Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukemia (CML).Many patients have deep molecular responses(DMR), a prerequisite for TKIs therapy discontinuation. Many clinical studies have been done in discontinuation of TKIs worldwide. We aimed to explore the appropriate criteria for failure of TKIs discontinuation; and to observe the effect of interferon on patients with continuous low level positive BCR-ABL1 after TKIs discontinuation. Therefore, we analyzed the clinical data of 40 CML patients with DMR who have withdrawn TKIs from Match 2013 to January 2018. Eligible CML patients had received any TKI for at least 3 years, and had a confirmed deep molecular response for at least 2 year. The molecular relapse(MR) was defined as loss of major molecular response (MMR; BCR-ABL1 〉 0.1% on the International Scale). The patients with MR would be prescribed TKI, and patients with 0.0032% 〈 BCR-ABL1IS 〈 0.1% would be suggested to try interferon. Of these 40 patients, male/female was 24/16, the median age was 50 (13,70) years, and 2 cases were accelerated phase, while the rest were chronic phase at diagnosis. It was feasible for Sokal score in 35 cases, including 18 cases with low risk, 12 with intermediate risk and 2 with high risk. The median time to MR4.5 was 18 (6,82) months, and the median duration of MR4.5 before TKIs discontinuation was 52 (27,115) months. Thirty-two patients had been taking imatinib and eight had been taking second-generation TKIs. The median duration of TKIs was 83.7 (37.5, 125.4) months. After drug withdrawal, median follow-up was 17.6 (6,65) months. 17 patients eventually lost MMR.TFR was 65% (95%CI (47.6%, 82.4%) at 12 months. A total of 14 patients restarted TKI treatment, 1 lost the visit, and 13 patients regained MMR or MR4.5 within 3 months after taking the medicine. There were 23 patients without losing MMR, 10 of whom maintained CMR. There were 5 cases with single positive BCR-ABL1 that did not lose MR4.Eight cases were positive for BCR-ABL1 more than twice, of which four lost MR4 (3 received interferon treatment) and four did not lose MR4 (1 received interferon treatment). Of the 21 patients with BCR-ABL1 positive for more than 2 times after discontinuation (4 patients were excluded for loss of MMR in first positive test), 6 patients by follow-up did not lose the MR4, in 15 cases losing MR4, 12 cases eventually lose the MMR, 3 cases of follow-up did not lose the MMR (2 cases received interferon treatment), TFR for two groups was statistically difference (P = 0.026).In these 21 patients, 3 cases were non continuous positive, 18 cases of low level 2 consecutive positive, the median follow-up of 15.75 (6,55.5) months, 7 cases received interferon therapy, median follow-up after application of interferon was 9 (3, 20) months, in which 2 cases eventually lose the MMR, 11 cases treated without interferon, 10 cases eventually lose the MMR, TFR was statistically different between the two groups (71.4% vs 9.1%, P 〈 0.001).Among them, 2 female patients lost MMR 4 months after drug withdrawal, and because of pregnancy they did not take TKI again, they were given interferon treatment, and obtained and maintained MMR 2 months after interferon treatment. Patients with interferon are well tolerated. After the discontinuation of TKI in CML patients, early intervention should be conducted if MR4 is lost, and interferon treatment may help maintain MMR and prolong the survival without TKI treatment. 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
    detail.hit.zdb_id: 80069-7
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  • 10
    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
    RVK:
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    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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