Imamura Toshihiko, Taga Takashi, Takagi Masatoshi, Kawasaki Hirohide, Koh Katsuyoshi, Taki Tomohiko, Adachi Souichi, Manabe Atsushi, Ishida Yasushi
Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan.
Int J Hematol. 2018 Jul;108(1):91-97. doi: 10.1007/s12185-018-2439-x. Epub 2018 Mar 24.
Therapy-related leukemia (t-leukemia) is associated with dismal prognosis. Published pediatric t-leukemia data are somewhat outdated and may not reflect recent advances in treatment. We report a retrospective nationwide survey of patients diagnosed between 2000 and 2013 in Japan. We identified 43 patients with pediatric t-leukemia; 33 had t-acute myeloid leukemia (t-AML), eight had t-acute lymphoblastic leukemia (t-ALL) and two had t-acute undifferentiated leukemia. Median age at onset and latency were 12 years and 3.8 years, respectively, consistent with previous reports. Of t-AML patients, 63.6% harbored topoisomerase II inhibitor (topo II)-related genetic abnormalities, while only 12.5% of t-ALL patients had such alterations, suggesting that topo II is not key to t-ALL leukemogenesis. The 7-year overall survival (OS) for all 43 patients was 39.2 ± 11.6%. The 5-year OS was 50 ± 20.4% in t-ALL, and 55.2 ± 11.0% in t-AML. Allogeneic hematopoietic cell transplantation (allo-HCT) was associated with superior 5-year OS (HCT(+) vs. HCT(-), 78.8 vs. 12.1%; p < 0.001), and 26 of 32 patients received allo-HCT in complete remission (CR). Only allo-HCT was associated with superior OS on multivariate analysis (HR 0.003, 95% CI 0.0001-0.098; p < 0.001). These findings suggest that allo-HCT in CR improves pediatric t-leukemia outcomes.
治疗相关白血病（t-白血病）的预后较差。已发表的儿童t-白血病数据有些过时，可能无法反映近期的治疗进展。我们报告了一项对2000年至2013年期间在日本确诊的患者进行的全国性回顾性调查。我们确定了43例儿童t-白血病患者；其中33例为t-急性髓系白血病（t-AML），8例为t-急性淋巴细胞白血病（t-ALL），2例为t-急性未分化白血病。发病年龄和潜伏期的中位数分别为12岁和3.8年，与先前的报告一致。在t-AML患者中，63.6%存在与拓扑异构酶II抑制剂（topo II）相关的基因异常，而t-ALL患者中只有12.5%有此类改变，这表明topo II不是t-ALL白血病发生的关键因素。43例患者的7年总生存率（OS）为39.2±11.6%。t-ALL的5年OS为50±20.4%，t-AML为55.2±11.0%。异基因造血细胞移植（allo-HCT）与5年OS较高相关（HCT(+)与HCT(-)，78.8%与12.1%；p<0.001），32例患者中有26例在完全缓解（CR）时接受了allo-HCT。多因素分析显示只有allo-HCT与较高的OS相关（风险比0.003，95%置信区间0.0001-0.098；p<0.001）。这些发现表明，CR期进行allo-HCT可改善儿童t-白血病的预后。
