Hunger S P, Link M P, Donaldson S S
Department of Pediatrics, Stanford University School of Medicine, CA 94305.
J Clin Oncol. 1994 Oct;12(10):2160-6. doi: 10.1200/JCO.1994.12.10.2160.
We reported previously that treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and 15 to 25 Gy irradiation was effective in curing children with Hodgkin's disease, but was associated with a 6.5% 10-year risk of development of secondary leukemia. Based on the results of that study, a successor study was designed with the objective to maintain treatment efficacy while decreasing adverse effects, particularly the occurrence of secondary leukemia.
Fifty-seven children with a chronologic and/or bone age less than 16 years were enrolled onto this study between May 1982 and October 1990. Treatment consisted of six cycles of combination chemotherapy--three of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and three of MOPP--and low-dose irradiation (15 Gy) of involved fields. Boosts of 10 Gy were given to areas of bulky disease and to those that did not respond completely after two cycles of chemotherapy.
With a median follow-up duration of 6.7 years, the projected 10-year survival and event-free survival (EFS) rates are 96% (SE 2.5%) and 93% (SE 3.5%) for the entire cohort of 57 patients, and 85% (SE 10%) and 69% (SE 12.8%), respectively, for 13 patients with stage IV disease. No patient has developed a second malignancy. Growth and development have progressed normally. No patients have symptomatic cardiac, pulmonary, or thyroid disease. Subclinical abnormalities of pulmonary function were detected in 32% and chemical hypothyroidism in 16%.
This therapy was highly efficacious in children with Hodgkin's disease without unacceptable toxicity. Future efforts should be directed toward further reducing therapy for favorable early-stage patients and improving treatment efficacy for those with stage IV disease.
我们之前报道过，采用六个周期的氮芥、长春新碱、丙卡巴肼和泼尼松（MOPP）化疗以及15至25戈瑞的放疗对霍奇金病患儿进行治疗，可有效治愈疾病，但会有6.5%的10年继发白血病风险。基于该研究结果，设计了一项后续研究，目标是在维持治疗效果的同时减少不良反应，尤其是继发白血病的发生。
1982年5月至1990年10月期间，57名年龄小于16岁（按实足年龄和/或骨龄计算）的儿童被纳入本研究。治疗包括六个周期的联合化疗——三个周期为多柔比星、博来霉素、长春花碱和达卡巴嗪（ABVD）方案，三个周期为MOPP方案——以及对受累野进行低剂量放疗（15戈瑞）。对大块病灶区域以及化疗两个周期后未完全缓解的区域给予10戈瑞的加强放疗。
中位随访时间为6.7年，57例患者的整个队列预计10年生存率和无事件生存率（EFS）分别为96%（标准误2.5%）和93%（标准误3.5%），13例IV期疾病患者的预计10年生存率和无事件生存率分别为85%（标准误10%）和69%（标准误12.8%）。没有患者发生第二种恶性肿瘤。生长发育正常进行。没有患者出现有症状的心脏、肺部或甲状腺疾病。32%的患者检测到亚临床肺功能异常，16%的患者检测到化学性甲状腺功能减退。
该疗法对霍奇金病患儿高度有效，且无不可接受的毒性。未来的工作应致力于进一步减少对预后良好的早期患者的治疗，并提高IV期疾病患者的治疗效果。
