骨髄芽球の増加を伴う高リスク骨髄異形成症候群の患者におけるアザシチジン療法の予後予測因子
骨髄異形成症候群（MDS）は無効造血と前白血病状態を特徴とし，その病態は多様である．azacitidineは脱メチル化作用を有し，高リスクMDSでは多剤併用化学療法に代わるEpigenetic therapyと位置付けられている．一方芽球増加（20～30％）を伴うMDS（refractory anemia with excess of blast（RAEB））においてazacitidineの治療療効果は症例間で差異が大きい．この群においてのazacitidine治療反応性の相違の背景となる分子基盤は明らかとなっていない．azacitidine療法をより適切に行う指針を得る目的で，当科でazac...
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| Published in | 昭和学士会雑誌 Vol. 77; no. 2; pp. 181 - 187 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
昭和大学学士会
2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2187-719X 2188-529X |
| DOI | 10.14930/jshowaunivsoc.77.181 |
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| Abstract | 骨髄異形成症候群（MDS）は無効造血と前白血病状態を特徴とし，その病態は多様である．azacitidineは脱メチル化作用を有し，高リスクMDSでは多剤併用化学療法に代わるEpigenetic therapyと位置付けられている．一方芽球増加（20～30％）を伴うMDS（refractory anemia with excess of blast（RAEB））においてazacitidineの治療療効果は症例間で差異が大きい．この群においてのazacitidine治療反応性の相違の背景となる分子基盤は明らかとなっていない．azacitidine療法をより適切に行う指針を得る目的で，当科でazacitidine療法を受けた22症例の臨床因子とazacitidine療法後の治療予後を後方視的に解析した．単変量解析において年齢≦80歳（p＝0.04），白血球数≦3,000/µl（p＝0.04），LDH正常値（p＝0.003），フェリチン値（p＝0.006），骨髄細胞密度（p＝0.003），線維化合併（p＝0.04），Early Hematological Improvement（EHI）（p＝0.009），Hematological Improvement with Neutrophil（HI-N）（p＝0.029），Hematological Improvement with platelet（HI-P）（p＝0.009）が生存期間延長と有意に相関していた．これらの臨床因子はazacitidine療法を選択する際に着目すべき重要性を持つと考えられた． |
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| AbstractList | 骨髄異形成症候群（MDS）は無効造血と前白血病状態を特徴とし，その病態は多様である．azacitidineは脱メチル化作用を有し，高リスクMDSでは多剤併用化学療法に代わるEpigenetic therapyと位置付けられている．一方芽球増加（20～30％）を伴うMDS（refractory anemia with excess of blast（RAEB））においてazacitidineの治療療効果は症例間で差異が大きい．この群においてのazacitidine治療反応性の相違の背景となる分子基盤は明らかとなっていない．azacitidine療法をより適切に行う指針を得る目的で，当科でazacitidine療法を受けた22症例の臨床因子とazacitidine療法後の治療予後を後方視的に解析した．単変量解析において年齢≦80歳（p＝0.04），白血球数≦3,000/µl（p＝0.04），LDH正常値（p＝0.003），フェリチン値（p＝0.006），骨髄細胞密度（p＝0.003），線維化合併（p＝0.04），Early Hematological Improvement（EHI）（p＝0.009），Hematological Improvement with Neutrophil（HI-N）（p＝0.029），Hematological Improvement with platelet（HI-P）（p＝0.009）が生存期間延長と有意に相関していた．これらの臨床因子はazacitidine療法を選択する際に着目すべき重要性を持つと考えられた． |
| Author | 柳澤, 孝次 中牧, 剛 塚本, 裕之 村井, 聡 斎藤, 文護 川口, 有紀子 蒲澤, 宣幸 阿部, 真麻 馬場, 勇太 荒井, 奈々 宇藤, 唯 服部, 憲路 綿貫, めぐみ |
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| References_xml | – reference: 6）Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013;48:452-458. – reference: 15）栗山一孝，吉田真一郎，今西大介，ほか．JALSGにおけるAMLの化学療法 スコアリングシステムを用いた予後判定．臨血．1998;39:98-102. – reference: 11）Ghoshal K, Datta J, Majumder S, et al. 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Mol Cell Biol. 2005;25:4727-4741. – reference: 5）Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group（IWG）response criteria in myelodysplasia. Blood. 2006;108:419-425. – reference: 7）Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079-2088. – reference: 1）Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med. 2009;361:1872-1885. – reference: 4）Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51:189-199. – reference: 12）Hollenbach PW, Nguyen AN, Brady H, et al. A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One（Internet）. 2010;5:e9001. （accessed 2016.7.14）https://doi.org/10.1371/journal.pone.0009001 – reference: 10）Welch JS, Petti AA, Miller CA, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375:2023-2036. – reference: 17）Barragan E, Cervera J, Bolufer P, et al. Prognostic implications of Wilms' tumor gene（WT1）expression in patients with de novo acute myeloid leukemia. Haematologica. 2004;89:926-933. – reference: 2）Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454-2465. – reference: 8）Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28:562-569. – reference: 9）Bejar R, Lord A, Stevenson K, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124:2705-2712. – reference: 14）Itzykson R, Thepot S, Quesnel B, et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117:403-411. – reference: 13）Khan R, Aggerholm A, Hokland P, et al. A pharmacodynamic study of 5-azacytidine in the P39 cell line. Exp Hematol. 2006;34:35-43. – reference: 16）Tsang E, Leitch HA. Pre- and post-treatment serum ferritin levels in patients with higher risk myelodysplastic syndromes receiving azacitidine. Leuk Lymphoma. 2016;57:2709-2711. – reference: 3）Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase Ⅲ study. Lancet Oncol. 2009;10:223-232. |
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| SubjectTerms | azacitidine 予後予測因子 骨髄異形成症候群 |
| Title | 骨髄芽球の増加を伴う高リスク骨髄異形成症候群の患者におけるアザシチジン療法の予後予測因子 |
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