A systematic review of treatment outcomes with weight-based dosing of chemotherapy in obese adult patients with acute leukemia or lymphoma
A systematic review of treatment outcomes with weight-based dosing of chemotherapy in obese adult patients with acute leukemia or lymphoma
复制标题
对患有急性白血病或淋巴瘤的肥胖成人患者基于体重的化疗剂量的治疗结果进行系统评价
作者：
S. Mapp;G. Sandhu;C. Carrington;S. Hennig
急性血液系统恶性肿瘤的大剂量化疗通常是为了治愈而开的处方。然而，治疗相关的毒性，如感染、长期骨髓抑制、神经毒性、肾损害、胃肠道毒性和心血管并发症，导致显著的发病率，在某些情况下导致死亡。平衡功效和毒性是一个持续的挑战。1980-2013年间，全球超重或肥胖成年人的患病率上升了28% [1]。体重指数（BMI），定义为体重（千克）除以身高（米）的平方，用于将超重定义为BMI 25 kg/m，肥胖定义为BMI 30 kg/m [2]。在超重和肥胖的血液学和肿瘤患者中，通常会减少基于体重的化疗剂量[3]。这是由于担心改变化疗药代动力学和过量的毒性在这一人群。虽然有许多文献综述了体重增加患者的治疗结局，但大多数文献未采集关于基于体重的剂量调整的信息。因此，无法充分解读结果以指导未来患者给药。本系统性文献综述旨在比较超重和肥胖成人患者与正常体重急性白血病或侵袭性淋巴瘤患者的治疗相关毒性和结局。目的是根据该人群的实际体重（ABW）确定化疗剂量的适当性。本综述未涉及新型靶向治疗的剂量。对4个数据库（PubMed、EMBASE、Web of Science和科克伦对照试验中心注册数据库）进行文献检索，以检索1995年至2014年底期间发表的英语文章。PubMed检索词为（肥胖 * 和急性骨髓 * 白血病）或（超重和急性骨髓 * 白血病）或（肥胖 * 和急性淋巴 * 白血病）或（超重和急性淋巴 * 白血病）或（肥胖 * 和淋巴瘤）或（超重和淋巴瘤）。EMBASE检索使用Emtree术语“肥胖”、“淋巴瘤”、“急性淋巴细胞白血病”和“急性粒细胞白血病”的组合，后者是数据库中急性髓细胞白血病的检索词。对于Web of Science和科克伦对照试验中心注册库检索，我们使用与PubMed检索相同的检索词和组合。两位作者（SM、GS）独立筛选标题，整理潜在相关文章，然后全文阅读，以确定其是否符合本综述的资格。分歧以协商一致方式解决。仅当详细描述了治疗结局（包括毒性、疾病缓解和/或生存期），使用了当前接受的化疗方案，并且评论称剂量基于体重，少数体重增加的患者（长春新碱除外）未调整或指定调整剂量时，才将已发表的文章纳入本综述。排除了干细胞移植研究，因为预处理化疗方案中的剂量通常是有意的清髓性，并且治疗相关毒性可能受到全身照射、免疫抑制和干细胞剂量的混淆。此外，最近发表了一项关于该人群的综合文献综述[4]。同样排除了儿科（定义为16岁以下）研究、文献综述、小型病例系列和病例报告、摘要和社论。使用该检索策略共识别出861项急性白血病研究和1098项淋巴瘤研究[图1]。在筛选标题和评价文章的潜在相关性后，只有5篇关于急性髓性白血病的文章和4篇关于淋巴瘤的文章符合要求
High dose chemotherapy for acute hematological malignancies is usually prescribed with curative intent. However, treatment-related toxicities such as infection, prolonged myelosuppression, neurotoxicity, renal impairment, gastrointestinal toxicity and cardiovascular complications cause significant morbidity and in some instances mortality. Balancing efficacy and toxicity is a constant challenge. Between 1980–2013, the worldwide prevalence of overweight or obese adults rose by 28% [1]. Body mass index (BMI), defined as weight in kilograms divided by square of height in meters, is used to define overweight as a BMI 25 kg/m and obese as a BMI 30 kg/m [2]. Weight-based chemotherapy doses have been commonly reduced in overweight and obese hematology and oncology patients [3]. This is due to concerns regarding altered chemotherapy pharmacokinetics and an excess of toxicity in this population. Whilst there are numerous publications reviewing treatment outcomes in patients of increased weight, most do not capture information regarding weightbased dose modifications. Consequently, results cannot be adequately interpreted to guide future patient dosing. This systematic review of the literature was performed to collate treatment-related toxicities and outcomes in overweight and obese adult patients compared to normal weight patients with acute leukemia or aggressive lymphoma. The aim was to determine the appropriateness of dosing chemotherapy according to actual body weight (ABW) in this population. Dosing of novel targeted therapies was not addressed in this review. A literature search of four databases (PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials) was conducted for English language articles published between 1995 and the end of 2014. The PubMed search terms were (obes* AND acute myel* leukemia) OR (overweight AND acute myel* leukemia) OR (obes* AND acute lymph* leukemia) OR (overweight AND acute lymph* leukemia) OR (obes* AND lymphoma) OR (overweight AND lymphoma). The EMBASE search used combinations of the Emtree terms ‘‘obesity’’, ‘‘lymphoma’’, ‘‘acute lymphoblastic leukemia’’ and ‘‘acute granulocytic leukemia’’, the latter being the database’s search term for acute myeloid leukemia. For the Web of Science and Cochrane Central Register of Controlled Trials searches we used the same search terms and combinations as for the PubMed search. Two authors (SM, GS) independently screened titles, collated potentially relevant articles and then read them in full in order to determine their eligibility for this review. Discrepancies were resolved by consensus. Published articles were only included in this review if treatment outcomes were detailed (including toxicities, disease response and/or survival), currently accepted chemotherapy regimens were used and a comment was made that doses were weight-based with no, or specified, modification of doses in a minority of patients of increased weight (except vincristine). Studies in stem cell transplantation were excluded because doses in conditioning chemotherapy regimens are often intentionally myeloablative and treatment-related toxicities could be confounded by total body irradiation, immunosuppression and stem cell dose. Furthermore, a comprehensive literature review in this population had been published recently [4]. Pediatric (defined as below 16 years of age) studies, literature reviews, small case series and case reports, abstracts and editorials were similarly excluded. A total of 861 acute leukemia studies and 1098 lymphoma studies were identified using this search strategy [Fig. 1]. Upon screening titles and evaluating the articles for potential relevance, only five articles for acute myeloid leukemia and four for lymphoma fulfilled
影响因子：
3.5
作者：
Lee, Hun Ju;Licht, Andrea S.;Hyland, Andrew J.;Ford, Laurie A.;Sait, Sheila N. J.;Block, AnneMarie W.;Barcos, Maurice;Baer, Maria R.;Wang, Eunice S.;Wetzler, Meir
通讯作者：
Wetzler, Meir