实体器官移植(SOT)后移植后淋巴增生性疾病(PTLD)的常见化疗方案是环磷酰胺,阿霉素,长春新碱,和泼尼松(CHOP)。本研究回顾了与儿童肿瘤学组长期随访指南中确定的CHOP成分相关的长期后果的定量证据。引用的参考文献使用预先指定的标准进行筛选(英文,系统审查,随机对照试验n>100,观察研究n>100,病例系列n>20)。提取并合成相关数据。在61项研究中,66%为回顾性队列研究,28%在美国,95%的儿童患者入组。没有专门针对CHOP方案的研究。在>3项研究中观察到的CHOP成分的长期后果包括心脏毒性(n=14),激素缺乏/不孕(n=14),继发性白血病(n=7),骨坏死(n=6),和膀胱癌(n=4)。这些影响是显著的,影响了很高比例的患者,并早在治疗后一年发生。尽管没有一项研究专门针对CHOP方案,30%,23%,和15%评估的烷化剂(例如环磷酰胺),蒽环类药物(如阿霉素),和皮质类固醇(例如泼尼松),分别。所有三个产品类别都具有剂量依赖性的长期后果风险,最高可达13.2倍,27倍,16倍,14.5倍,心力衰竭的风险增加6.2倍,更年期提前,继发性白血病,膀胱癌,和骨坏死,分别。淋巴瘤患者的心脏毒性风险显着升高(高达12.2倍),卵巢功能衰竭(高达3.8倍),和骨坏死(高达6.7倍)。没有发现PTLD或SOT的研究。迫切需要有可能避免这些长期后果的安全有效的PTLD治疗。
A common chemotherapy regimen in post-transplant lymphoproliferative disease (PTLD) following solid organ transplants (SOT) is cyclophosphamide, doxorubicin, vincristine, and prednisone (
CHOP). This study reviews the quantitative evidence for long-term consequences associated with components of
CHOP identified from the Children\'s Oncology Group Long-Term Follow-Up Guidelines. Cited references were screened using prespecified criteria (English, systematic
review, randomized controlled trial n > 100, observation study n > 100, case series n > 20). Relevant data were extracted and synthesized. Of 61 studies, 66% were retrospective cohort studies, 28% were in the US, and 95% enrolled pediatric patients. No study focused specifically on the
CHOP regimen. Long-term consequences for
CHOP components observed in >3 studies included cardiac toxicity (n = 14), hormone deficiencies/infertility (n = 14), secondary leukemia (n = 7), osteonecrosis (n = 6), and bladder cancer (n = 4). These effects are significant, impact a high percentage of patients, and occur as early as one year after treatment. Although none of the studies focused specifically on the CHOP regimen, 30%, 23%, and 15% evaluated alkylating agents (e.g. cyclophosphamide), anthracyclines (e.g. doxorubicin), and corticosteroids (e.g. prednisone), respectively. All three product classes had a dose-dependent risk of long-term consequences with up to 13.2-fold, 27-fold, 16-fold, 14.5-fold, and 6.2-fold increase in risk of heart failure, early menopause, secondary leukemia, bladder cancer, and osteonecrosis, respectively. Lymphoma patients had significantly elevated risks of cardiac toxicity (up to 12.2-fold), ovarian failure (up to 3.8-fold), and osteonecrosis (up to 6.7-fold). No studies were found in PTLD or SOT. Safe and effective PTLD treatments that potentially avoid these long-term consequences are urgently needed.