Treating childhood acute lymphoblastic leukemia without cranial irradiation.
Treating childhood acute lymphoblastic leukemia without cranial irradiation.
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DOI：
10.1056/nejmoa0900386
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发表时间：
2009-06-25
期刊：
影响因子：
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通讯作者：
Relling MV
中科院分区：
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作者：
Pui CH;Campana D;Pei D;Bowman WP;Sandlund JT;Kaste SC;Ribeiro RC;Rubnitz JE;Raimondi SC;Onciu M;Coustan-Smith E;Kun LE;Jeha S;Cheng C;Howard SC;Simmons V;Bayles A;Metzger ML;Boyett JM;Leung W;Handgretinger R;Downing JR;Evans WE;Relling MV
我们进行了一项临床试验，以测试是否预防性颅照射可以省略所有儿童新诊断的急性淋巴细胞白血病。共入组498例可评价患者。治疗强度基于缓解诱导治疗后的表现特征和微小残留病水平。比较了71例既往接受过预防性颅照射的患者和56例接受过预防性颅照射的历史对照患者的持续完全缓解情况。所有498例患者的平均生存率（95%置信区间）分别为85.6%（79.9%至91.3%）和93.5%（89.8%至97.2%）。孤立性中枢神经系统（CNS）复发的5年累积风险为2.7%（1.1%至4.2%），任何CNS复发（孤立性加合并）的5年累积风险为3.9%（1.9%至5.9%）。71例患者的持续完全缓解显著优于56例历史对照（P = 0.04）。所有11例孤立性CNS复发患者均保持第二次缓解0.4至5.5年。CNS白血病（CNS-3状态）或诊断时有原始细胞的创伤性腰椎穿刺和缓解诱导6周后高水平的微小残留病（≥ 1%）与无事件生存率较差显著相关。CNS复发的危险因素包括存在t（1; 19）[TCF 3-PBX 1]、诊断时任何CNS受累和T细胞免疫表型。常见的不良反应包括对左旋门冬酰胺酶的过敏反应、骨坏死、血栓形成和播散性真菌感染。通过有效的风险调整化疗，在治疗儿童急性淋巴细胞白血病时可以安全地省略预防性颅照射。
We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia.