Meadows A T, Obringer A C, Marrero O, Oberlin O, Robison L, Fossati-Bellani F, Green D, Voûte P A, Morris-Jones P, Greenberg M
Children's Hospital of Philadelphia, Pennsylvania 19104.
Med Pediatr Oncol. 1989;17(6):477-84.
The risk of second malignant neoplasm (SMN) was evaluated in 979 children with Hodgkin's disease. This cohort was diagnosed between 1955 and 1979 at one of the institutions of the Late Effects Study Group. Solid tumors, non-lymphocytic leukemia, and non-Hodgkin's lymphoma (NHL) developed in 18, 17, and 3 patients, respectively. The estimated cumulative probability of developing any SMN was 2% at 5 years from diagnosis, 5% at 10 years, and 9% at 15 years. The incidence is ninefold greater than the risk of acquiring cancer in 19 year-olds, the median age at which the diagnosis of SMN was made in this study population. For leukemia and NHL the corresponding probabilities were 1%, 3%, and 4% for the group as a whole but were increased (2%, 6%, and 8%) in patients who had suffered one or more recurrences. In order to analyze the risk of leukemia and NHL associated with alkylating agent chemotherapy, each patient was assigned a score of one for each alkylating agent administered for a 6-month period. Scores of 2, 4, 6, and 8 were associated with probabilities of leukemia or NHL of 2%, 3%, 6%, and 10%, respectively. In a multivariate analysis for leukemia/lymphoma that included AAD score, stage, and splenectomy, the effect of AAD score and splenectomy did not change substantially compared to the univariate results. AAD score remained statistically significant (P = .0001), and splenectomy was of borderline significance (P = .09). Of the 18 solid tumor SMNs, 15 developed within the field of radiation, and one other developed in tissue irradiated 34 years earlier for hemangioma. This study of a large and unselected group of children with Hodgkin's disease who received a variety of therapies demonstrates that children are as likely as adults to develop acute leukemia after alkylating agents and solid tumors in the field of radiation therapy.
对979例霍奇金病患儿的第二原发性恶性肿瘤（SMN）风险进行了评估。该队列于1955年至1979年间在晚期效应研究组的其中一家机构被诊断。分别有18例、17例和3例患儿发生实体瘤、非淋巴细胞白血病和非霍奇金淋巴瘤（NHL）。估计从诊断起5年时发生任何SMN的累积概率为2%，10年时为5%，15年时为9%。该发病率比19岁人群患癌风险高9倍，19岁是本研究人群中诊断SMN的中位年龄。对于白血病和NHL，整个组的相应概率分别为1%、3%和4%，但在经历一次或多次复发的患者中有所增加（2%、6%和8%）。为了分析与烷化剂化疗相关的白血病和NHL风险，为每位患者在每6个月使用一种烷化剂时赋予1分。2分、4分、6分和8分分别与白血病或NHL的概率2%、3%、6%和10%相关。在一项包括烷化剂累积剂量（AAD）评分、分期和脾切除术的白血病/淋巴瘤多因素分析中，与单因素结果相比，AAD评分和脾切除术的影响没有实质性变化。AAD评分仍具有统计学意义（P = 0.0001），脾切除术具有临界意义（P = 0.09）。在18例实体瘤SMN中，15例发生在放疗区域内，另一例发生在34年前因血管瘤接受放疗的组织中。这项对一大组未经选择且接受多种治疗的霍奇金病患儿的研究表明，儿童在接受烷化剂治疗后发生急性白血病以及在放射治疗区域发生实体瘤的可能性与成人相同。
