Department of Pediatrics, Weill Cornell Medical College, New York, NY.
Department of Biostatistics, University of Florida, Gainesville, FL.
Blood. 2021 Mar 18;137(11):1449-1456. doi: 10.1182/blood.2020007225.
Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs). Response-adapted treatment may decrease this risk by reducing exposure to therapy associated with SMN risk. The Children's Oncology Group study AHOD0031 evaluated response-adapted therapy for children and adolescents with intermediate-risk HL. We report the SMNs among 1711 patients enrolled in AHOD0031. Patients were treated with 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without involved-field radiation therapy (RT). Patients with a slow early response to initial chemotherapy were randomized to 2 additional cycles of dexamethasone, etoposide, cisplatin and cytarabine or no additional chemotherapy, and all received RT. At a median follow-up of 7.3 years, an analysis of SMNs was performed. The 10-year cumulative incidence of SMN was 1.3% (95% confidence interval [CI], 0.6-2.0). SMNs included 3 patients with acute myeloid leukemia (AML), 11 with solid tumors, and 3 with non-Hodgkin lymphoma. Sixteen of 17 patients with an SMN had received combined modality therapy. The standardized incidence ratio for SMN was 9.5 (95% CI, 4.5-15.2) with an excess absolute risk of 1.2 per 1000 person-years. The cumulative incidence of SMNs was higher among patients who received RT (P = .037). In multivariate analysis, RT, B symptoms, and race were associated with SMN risk. Given the latency from exposure, we have likely captured all cases of secondary leukemia and myelodysplastic syndrome (MDS). Longer follow-up is needed to determine the risk of solid tumors. Avoidance of RT without sacrificing disease control should remain a goal for future therapeutic approaches. This trial was registered at www.clinicaltrials.gov as #NCT00025259.
霍奇金淋巴瘤（HL）幸存者存在随后发生恶性肿瘤（SMN）的风险增加。通过减少与 SMN 风险相关的治疗暴露，适应反应的治疗可能会降低这种风险。儿童肿瘤学组研究 AHOD0031 评估了适应反应的治疗方法，用于治疗中危 HL 的儿童和青少年。我们报告了在 AHOD0031 中入组的 1711 例患者中的 SMN。患者接受了 4 个周期的多柔比星、博来霉素、长春新碱、依托泊苷、泼尼松和环磷酰胺，加或不加累及野放疗（RT）。对初始化疗反应缓慢的患者进行随机分组，接受 2 个周期的地塞米松、依托泊苷、顺铂和阿糖胞苷或不接受额外化疗，所有患者均接受 RT。中位随访 7.3 年后，进行了 SMN 的分析。SMN 的 10 年累积发生率为 1.3%（95%CI，0.6-2.0）。SMN 包括 3 例急性髓系白血病（AML）、11 例实体瘤和 3 例非霍奇金淋巴瘤。17 例 SMN 患者中有 16 例接受了联合治疗。SMN 的标准化发病比为 9.5（95%CI，4.5-15.2），超额绝对风险为每 1000 人年 1.2 例。接受 RT 的患者 SMN 的累积发生率更高（P =.037）。多变量分析显示，RT、B 症状和种族与 SMN 风险相关。鉴于潜伏期，我们可能已经捕获了所有继发性白血病和骨髓增生异常综合征（MDS）的病例。需要更长时间的随访才能确定实体瘤的风险。在不牺牲疾病控制的情况下避免 RT 应仍然是未来治疗方法的目标。该试验在 www.clinicaltrials.gov 上注册为 #NCT00025259。
