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  • American Society of Hematology  (2)
  • 2015-2019  (2)
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  • American Society of Hematology  (2)
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  • 2015-2019  (2)
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  • 1
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5432-5432
    Abstract: Introduction Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. Methods The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. Patients with secondary MDS, chronic myelomonocytic leukaemia, and patients with AML and a BM blast count of 20-30% who were classified as having refractory anaemia with excess blast (RAEB)-t according to the French-American-British classification were excluded. Cytogenetic aberrations were counted following the International Working Group on MDS Cytogenetics (IWGMC) consensus guidelines. Complex karyotype (CK) was defined as having 3 or more chromosomal abnormalities. Monosomal karyotype (MK) was defined as the presence of 2 or more autosomal monosomies or 1 single autosomal monosomy in combination with structural abnormalities. Results The median age of the patients was 65 years, and 457 (61.9%) were male. The median follow-up time was 71.7 months for survivors (range, 0.1 - 230.5). The most common WHO subtype was refractory cytopaenia with multilineage dysplasia (29.7%), followed by RAEB-1 (19.8%), RAEB-2 (18.4%), refractory cytopaenia with unilineage dysplasia (15.4%), and MDS-unclassifiable (11.9%). More than half of patients received disease-modifying treatment; 381 (50.7%) received hypomethylating agents (HMAs), and 83 (11.1%) received haematopoietic stem cell transplantation (HSCT). IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations. Among these, 46 translocations involving 72 breakpoints were identified including balanced translocations in 13 (28.3%) and unbalanced translocation in 33 (71.7%). Translocations were found as a part of CK in 30/46 cases (65.2%) and as a part of MK in 21/46 (45.7%). Frequently involved chromosomes were chromosome 7 (n = 13); ch1 (n = 12); ch5 (n = 9); ch12 (n = 6); ch6, ch11, and ch14 (n = 5); ch10 and ch20 (n = 4); and ch16, ch17, and X (n = 3) in decreasing order. To the best of our knowledge, 43 (93.5%) of the 46 translocations have not been previously described in MDS, nor in AML or CMML. Patients with translocation also had a higher percentage of BM blasts and included a significantly larger proportion of RAEB-1 and RAEB-2. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P 〈 0.01), and multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06-2.63] ; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06-2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Conclusion Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment. Further studies in other populations are needed to validate the clinical relevance of translocation in patients with MDS. Disclosures Lee: Amgen: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    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. 3876-3876
    Abstract: Upfront allogeneic hematopoietic cell transplantation (alloHCT) as first line therapy for older than 40 or 50 years is not usually recommended for severe aplastic anemia patients even though there are suitable matched sibling donors because they usually have poor outcomes after alloHCT. Therefore, first line immune suppression therapy (IST) is recommended. However, current outstanding alloHCT outcome can make it possible to try upfront alloHCT even in older AA patients. The purpose of this retrospective study is to determine the transplantation-related results in AA patients older than 40 years. This study collected data retrospectively for older AA patients. Congenital bone marrow failure was excluded from this study. alloHCT was divided as upfront and second alloHCT according to prior IST. Total 129 patients were enrolled in this study from 2001 to 2017. Age at diagnosis and at alloHCT were 25 to 63 (median 48.0) years and 40.3-64.9 (median 49.1) years, respectively. Median time from diagnosis to alloHCT was 5.2 (range, 1-234.1) months. Upfront and second alloHCT were 42 and 87 patients, respectively. Upfront alloHCT received more stem cells from related donors, more BM stem cells and more fludarabine conditioning compared with second alloHCT (83.3% vs. 58.6%, p=0.005; 52.4% vs. 74.7%, p=0.011; 52.4% vs. 30.2%, p=0.015, respectively). However, ABO mismatching (p=0.747), TBI conditioning (p=0.547), cyclophosphamide conditioning (p=0.114), ATG conditioning (p=0.483) were similar between upfront and second alloHCT. Any engraftment failure, neutrophil engraftment failure and platelet engraftment failure were similar between upfront and second alloHCT (28.6% vs. 28.7%, p=0.985; 19.0% vs. 18.4%, p=0.928; 19.0% vs. 34.5%, p=0.072). Hepatic SOS, acute GvHD and chronic GvHD were also similar between upfront and second alloHCT (4.8% vs. 5.7%, p=0.817; 28.6% vs. 36.5%, p=0.376; 19.0% vs. 19.5%, p=0.947). Survival rates at 1Y, 2Y, 3Y and 5Y were 90.7, 82.2, 73.5 and 64.3%, respectively. Survival rates at 5 years in upfront and second alloHCT were 76.2 and 54.1%, respectively (p=0.059). Survival rates at 5 years (5YSR) in age 40-50y, 50-60y, and older than 60y were 64.1, 62.4 and 50.0%, respectively (p=0.349). alloHCT from matched related donor or other donors had similar survival rates (p=0.404). However, upfront alloHCT showed superior survival rate (5YSR 76.5% vs. 53.2%, p=0.114) without statistical significance compared with second alloHCT even in matched related donor subgroup. This trend is similar in alternative donor subgroup (5YSR 75.0% in upfront alloHCT vs. 54.9% in second alloHCT, p=0.459). alloHCT in older AA showed promising results even in patient older than 60 years although upfront alloHCT showed marginal statistical superiority. In conclusion, upfront alloHCT in older AA needs further confirmation by prospective studies. 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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