アブストラクト
Japanese
| Title | 急性リンパ性白血病 : 最新の知見 |
|---|---|
| Subtitle | 総説 |
| Authors | 真部淳 |
| Authors (kana) | |
| Organization | 北海道大学大学院医学研究院小児科学教室 |
| Journal | 日本造血細胞移植学会雑誌 |
| Volume | 10 |
| Number | 2 |
| Page | 72-80 |
| Year/Month | 2021 / |
| Article | 報告 |
| Publisher | 日本造血細胞移植学会 |
| Abstract | ALLの治療成績は大きく改善したが, 難治例の治療, 抗がん剤の毒性軽減のために新薬導入が必要である. Ph陽性ALL患者に対してはイマチニブと化学療法の併用によってHSCTを回避出来る可能性が示唆されている. またPh-like ALLでもABLやPDGFRBなどのチロシンキナーゼ遺伝子転座を有する例でTKIの有用性が示された. B細胞型ALLの再発・難治例に対しては免疫療法として, ブリナツモマブ抗体投与とCAR-T細胞療法が保険収載された. 6メルカプトプリンの代謝はNUDT15の遺伝子多型に依存することがわかり, その検査が保険収載された. 一方ALL治療後に二次がんを来たしやすい遺伝性素因 (TP53など) もわかってきた. 今後, ゲノム医療の進歩により, ALLの発症機転, 芽球の薬剤感受性, 薬物による毒性, 二次がんを来たしやすい素因などが統括的に明らかにされ, 個別化医療の一層の進展が期待される. |
| Practice | 臨床医学：内科系 |
| Keywords | 急性リンパ性白血病, 白血病ゲノム, 免疫療法, GWAS, 個別化医療 |
English
| Title | Recent advances in acute lymphoblastic leukemia |
|---|---|
| Subtitle | |
| Authors | Atsushi Manabe |
| Authors (kana) | |
| Organization | Department of Pediatrics, Hokkaido University Graduate School of Medicine |
| Journal | Journal of Hematopoietic Cell Transplantation |
| Volume | 10 |
| Number | 2 |
| Page | 72-80 |
| Year/Month | 2021 / |
| Article | Report |
| Publisher | The Japan Society for Hematopoietic Cell Transplantation |
| Abstract | [Abstract] Although the outcome of patients with ALL has dramatically improved, we still need novel therapy to treat refractory cases and reduced toxicities of conventional therapy in ALL patients. Imatinib-combined with chemotherapy resulted in a good outcome and some patients with Ph-positive ALL may not need HSCT. Tyrosine kinase inhibitors could also be used for those with Ph-like ALL having ABL and PDGFRB translocations. Immunotherapy such as blinatumomab bispecific antibody and CAR-T cell treatment have been developed and are recently covered by health insurance in Japan. NUDT15 polymorphism is appreciated as a major role player in 6-mercaptopirine metabolism and genetic polymorphism examination is recently covered by health insurance in Japan. The prevalence of cancer predisposition genes has recently been extensively studied and some genes such as TP53 is also involved in ALL leukemogenesis and therapy-related cancer may be another important issue in leukemia treatment. Thus, the development of genomic medicine will not only expand our knowledge but also contribute to personalized medicine in the context of leukemogenesis, sensitivity to drugs, toxicity, and subsequent occurrence of secondary cancer. |
| Practice | Clinical internal medicine |
| Keywords | GWAS |
- 全文ダウンロード： 従量制、基本料金制の方共に770円(税込) です。
参考文献
- 1. Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatr Int. 2018; 60: 4-12.
- 2. Tomizawa D, Miyamura T, Imamura T, et al. A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial. Blood. 2020; 136: 1813-1823.
- 3. Hayakawa F, Sakura T, Yujiri T, et al. Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following streatment with a pediatric protocol. A phase II study by the Japan Adult Leukemia Study Group. Blood Cancer J. 2014; 4: e252.
- 4. Toyoda Y, Manabe A, Tsuchida M, et al. Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood. J Clin Oncol. 2000; 18: 1508-1516.
- 5. Kato M, Ishimaru S, Seki M, et al. Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children. Leukemia. 2017; 31: 580-584.
残りの21件を表示する
- 6. Qian M, Cao X, Devidas M, et al. TP53 germline variations influence the predisposition and prognosis of B-cell acute lymphoblastic leukemia in children. J Clin Oncol. 2018; 36: 591-599.
- 7. Schultz KR, Carroll A, Heerema NA, et al. Long-trem followup of imatinib in pediatric Philadelphia choromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AAL0031. Leukemia. 2014; 28: 1467-1471.
- 8. Roberts KG, Li Y, Payne-Turner D. et al. Targetable kinaseactivating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014: 371: 1005-1015.
- 9. Hirabayashi S, Ohki K, Nakabayashi K, et al. ZNF384-related fusion genes consist of a subgroup with a characteristic immunophenotype in childhood B-cell precursor acute lymphoblastic leukemia. Haematologica. 2017; 102: 118-129.
- 10. Ohki K, Kiyokawa N, Saito Y, et al. Clinical and molecular characteristics of MEF2D fusion-positive precursor B-cell acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion. Haematologica. 2019; 104: 128-137.
- 11. Hirabayashi S, Butler ER, Ohki K, et al. Clinical characteristics and outcomes of B-ALL with ZNF384 rearrangements: A retrospective analysis by the Ponte di Legno Childhood ALL Working Group. Leukemia, in press
- 12. Relling MV, Hancock ML, Rivera GK, et al. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst. 1999; 91: 2001-2008.
- 13. Yang SK, Hong M, Baek J, et al. A common missense variant in NUDT15 confirs susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014; 46: 1017-1020.
- 14. Yang JJ, Landier W, Yang W, et al. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intplerance in children with acute lymphoblastic leukemia. J Clin Oncol. 2015; 33: 1235-1242.
- 15. Tanaka Y, Kato M, Hasegawa D, et al. Susceptibility to 6-MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukemia. Br J Haematol. 2015; 171: 109-115.
- 16. 歌野智之, 田中庸一, 木津純子, ほか. 小児急性リンパ性白血病の維持療法期間におけるメルカプトプリン及びメトトレキサート投与量の推移. 小児血液・がん学会雑誌. 2015; 52: 399-404.
- 17. von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/Phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016; 34: 4381-4389.
- 18. Brown PA, Lingyun Ji, Xinxin Xu, et al. A Randomized Phase 3 Trial of Blinatumomab Vs. Chemotherapy As Post-Reinduction Therapy in High and Intermediate Risk(HR/IR)First Relapse of B-Acute Lymphoblastic Leukemia(B-ALL) in Children and Adolescents/Young Adults(AYAs)Demonstrates Superior Efficacy and Tolerability of Blinatumomab: A Report from Children's Oncology Group Study AALL1331. Blood. 2019; 34(Supplement 2): LBA-1.
- 19. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoblastic leukemia. N Engl J Med. 2013; 368: 1509-1518.
- 20. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018; 378: 439-448.
- 21. 平松英文, 加藤格, 梅田雄嗣, 足立壮一, 滝田順子. 急性リンパ性白血病に対するCAR-T細胞療法. 日本造血細胞移植学会雑誌. 2020; 9: 93-99.
- 22. Grupp S, Hu Z-H, Zhang Y, et al. Tisagenlecleucel chimeric antigen receptor(CAR)T-cell therapy for relapsed/refractory children and young adults with acute lymphoblastic leukemia (ALL): Real world experience from the Center for International Blood and Marrow Transplantation Research (CIBMTR) and Cellular Therapy (CT) registry. Blood. 2019; 134 (Supplement 1): 2619.
- 23. Rubinstein JD, Nelson AS, Krupski C, et al. Chimeric antigen receptor T-cell therapy in patients with neurologic comorbidities. Pediatr Blood Cancer. 2020; 67: e28199.
- 24. Mullighan CG, Phillips LA, Su X, et al. Genomic analysis of the clonal origins of relapse of relapsed acute lymphoblastic leukemia. Science. 2008; 322: 1377-1380.
- 25. Moriyama T, Relling MV, Yang JJ. Inherited genetic variation in childhood acute lymphoblastic leukemia. Blood. 2015; 125: 3988-3995.
- 26. Urayama K, Takagi M, Kawaguchi T, et al. Regional evaluation of childhood acute lymphoblastic leukemia genetic susceptibility loci among Japanese. Sci Rep. 2018: 8: 789.
