Division of Pediatric Hematology/Oncology, The Brooklyn Hospital Center, Brooklyn, New York 11201, USA.
Paediatr Drugs. 2010 Apr 1;12(2):85-98. doi: 10.2165/11316170-000000000-00000.
Hodgkin lymphoma is one of the few cancers that affect both adults and children. Cure rates for Hodgkin lymphoma remain among the best for pediatric cancers. However, cure is often associated with significant delayed effects of therapy, including an elevated risk for second malignancies, cardiotoxicity, pulmonary toxicity, and gonadal and non-gonadal endocrine dysfunction. Therefore, the aim of current treatment strategies is to further improve outcomes while minimizing therapy-related complications. At diagnosis, patients are classified into risk groups based on disease stage, and the presence of clinical, biologic, and serologic risk factors. In general, the most recent trials have intensified therapy in those patients with high-risk disease to improve disease control, and have limited therapy in those patients with low-risk disease to avoid secondary effects. In low-risk patients, multiple studies have been conducted to investigate limiting either radiation therapy or chemotherapy to prevent long-term side effects without affecting the excellent cure rate. In intermediate- and high-risk patients, many studies have examined intensifying therapy to improve event-free survival rates. In addition, response assessment by fluorine-18-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) may be particularly important in pediatric Hodgkin lymphoma; it may allow modification of treatment to maximize treatment efficacy and minimize late effects of chemotherapy and radiation therapy. Despite the improvements in treatment for all stages of Hodgkin lymphoma, there is still a subgroup of patients who do not enter remission with initial therapy or relapse after initial response to therapy. Unfortunately, standard-dose salvage chemotherapy for relapsed disease has disappointing results in terms of overall survival since patients have typically already received intensive therapy. While there is no standard of care in terms of salvage chemotherapy, high-dose chemotherapy with autologous stem cell transplant (ASCT) rescue has become the standard of care for the majority of children with relapsed Hodgkin lymphoma. The use of allogeneic transplantation is controversial in relapsed or refractory Hodgkin lymphoma; because of the high transplant-related mortality, allogeneic transplant has not been associated with improved overall survival over ASCT. As more has been learned about the biologic mechanisms involved in Hodgkin lymphoma, biologically-based therapies are being investigated for use in this disease, both at initial diagnosis and relapse. Both immunotherapy and small molecules are being studied as possible therapeutic agents in Hodgkin lymphoma. Unfortunately, the vast majority of investigations of novel agents have occurred exclusively in adult patients. However, since pediatric Hodgkin lymphoma and adult Hodgkin lymphoma are similar, these results may potentially be extrapolated to pediatric Hodgkin lymphoma.
霍奇金淋巴瘤是少数同时影响成人和儿童的癌症之一。霍奇金淋巴瘤的治愈率仍然是儿科癌症中最高的之一。然而,治愈通常与治疗的显著延迟效应有关,包括二次恶性肿瘤、心脏毒性、肺毒性、性腺和非性腺内分泌功能障碍的风险增加。因此,目前治疗策略的目标是在最大限度地减少治疗相关并发症的同时,进一步提高疗效。在诊断时,根据疾病分期和临床、生物学和血清学危险因素,患者被分为风险组。一般来说,最近的试验已经加强了高危疾病患者的治疗,以改善疾病控制,并限制了低危疾病患者的治疗,以避免二次效应。在低危患者中,已经进行了多项研究,以调查限制放疗或化疗的范围,以防止长期副作用,而不影响卓越的治愈率。在中高危患者中,许多研究都在研究加强治疗,以提高无事件生存率。此外,氟-18-2-氟-2-脱氧-D-葡萄糖正电子发射断层扫描(FDG-PET)的反应评估在儿科霍奇金淋巴瘤中可能特别重要;它可以改变治疗,以最大限度地提高治疗效果,最大限度地减少化疗和放疗的晚期效应。尽管霍奇金淋巴瘤各期的治疗都有所改善,但仍有一部分患者在初始治疗后未进入缓解期或初始治疗缓解后复发。不幸的是,对于复发疾病的标准剂量挽救化疗,从总体生存的角度来看,结果并不令人满意,因为患者通常已经接受了强化治疗。虽然在挽救化疗方面没有标准的护理,但对于大多数复发霍奇金淋巴瘤患者来说,高剂量化疗联合自体干细胞移植(ASCT)已成为标准的护理。同种异体移植在复发或难治性霍奇金淋巴瘤中存在争议;由于移植相关死亡率高,同种异体移植与 ASCT 相比并未提高总体生存率。随着对霍奇金淋巴瘤涉及的生物学机制的了解越来越多,基于生物学的疗法正在被研究用于这种疾病,无论是在初始诊断还是复发时。免疫疗法和小分子都被研究为霍奇金淋巴瘤的可能治疗药物。不幸的是,绝大多数新型药物的研究仅在成年患者中进行。然而,由于儿科霍奇金淋巴瘤和成人霍奇金淋巴瘤相似,这些结果可能潜在地推广到儿科霍奇金淋巴瘤。
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