Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues.
Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues.
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DOI：
10.1002/cncr.23988
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发表时间：
2009-01-01
期刊：
影响因子：
6.2
通讯作者：
Hudson MM
中科院分区：
文献类型：
--
作者：
Hijiya N;Ness KK;Ribeiro RC;Hudson MM
继发性急性白血病对于接受过癌症治疗的儿童和青少年来说是一种毁灭性的并发症。继发性急性淋巴细胞白血病（s-ALL）以前很少报道，但现在可以通过比较免疫球蛋白和t细胞受体重排来区分复发性原发性ALL。继发性急性髓性白血病（s-AML）更为常见，有些病例实际上可能是第二原发癌症。治疗和宿主相关特征及其相互作用已被确定为s-AML的危险因素。最广泛认识的治疗相关危险因素是烷基化剂和拓扑异构酶II抑制剂（表观卟啉毒素和蒽环类药物）。与这些因素相关的风险程度取决于几个变量，包括给药计划、伴随用药和宿主因素。高累积剂量的烷基化剂是众所周知的易患s-AML。随着烷基化剂累积剂量的减少和更致白血病的烷基化剂的有限使用，烷基化剂相关s-AML的患病率在儿科肿瘤患者中有所下降。最具文献记录的拓扑异构酶II抑制剂相关的s-AML是与表皮毒素相关的s-AML。在这些病例中，s-AML的风险受到给药计划和与其他抗肿瘤药物的相互作用的影响，但与累积剂量并不一致。尽管预防复发的益处可能大于s-AML的风险，但表观臼毒素治疗后s-AML的不可预测风险可能会阻碍这些药物的使用，即使在复发风险高的患者中也是如此。对成人癌症幸存者的研究表明，与先前的观点相反，当调整细胞遗传学特征时，s-AML的结果并不一定比新生AML更差。需要更多的研究来证实这一发现在儿科患者群体中。
Secondary acute leukemia is a devastating complication in children and adolescents who have been treated for cancer. Secondary acute lymphoblastic leukemia (s-ALL) was previously rarely reported but can now be distinguished from recurrent primary ALL by comparison of immunoglobulin and T-cell receptor rearrangement. Secondary acute myeloid leukemia (s-AML) is much more common, and some cases may actually be second primary cancers. Treatment- and host-related characteristics and their interactions have been identified as risk factors for s-AML. The most widely recognized treatment-related risk factors are alkylating agents and topoisomerase II inhibitors (epipodophyllotoxins and anthracyclines). The magnitude of the risk associated with these factors depends on several variables, including the administration schedule, concomitant medications, and host factors. A high cumulative dose of alkylating agents is well known to predispose to s-AML. The prevalence of alkylator-associated s-AML has diminished among pediatric oncology patients with the reduction of cumulative alkylator dose and limited use of the more leukemogenic alkylators. The best-documented topoisomerase II inhibitor–associated s-AML is s-AML associated with epipodophyllotoxins. The risk of s-AML in these cases is influenced by the schedule of drug administration and by interaction with other antineoplastic agents but is not consistently related to cumulative dose. The unpredictable risk of s-AML after epipodophyllotoxin therapy may discourage the use of these agents even in patients at high risk of relapse, although the benefit of relapse prevention may outweigh the risk of s-AML. Studies in survivors of adult cancers suggest that contrary to previous beliefs, the outcome of s-AML is not necessarily worse than that of de novo AML when adjusted for cytogenetic features. More studies are needed to confirm this finding in the pediatric patient population.
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