Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna, Sant'Orsola Malpighi Hospital, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Transplant Cell Ther. 2021 Feb;27(2):180.e1-180.e8. doi: 10.1016/j.jtct.2020.11.006. Epub 2020 Dec 13.
Nutritional support for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely debated. Enteral nutrition (EN) is recommended as first-line nutritional support by the main international guidelines. However, these recommendations are based on weak evidence, and there is wide variability in the types of nutritional support among transplantation centers, with the majority providing parenteral nutrition (PN) instead of EN. Here we provide an up-to-date systematic review and meta-analysis of studies comparing EN and PN for nutritional support during the neutropenic period after allo-HSCT. The literature search strategy identified 13 papers, of which 10 compared clinical transplantation outcomes, 2 compared gut microbiota (GM) compositions, and 1 compared systemic metabolic profiles. For the meta-analysis, among the 10 clinical studies, 8 studies in which 2 groups were compared were selected: in 1 group, EN was provided as primary nutritional support in the neutropenic phase after allo-HSCT with or without the addition of PN (EN group), whereas in the other group, only PN was provided as nutritional support. The incidence rates of acute graft-versus-host disease (aGVHD) (relative risk [RR], 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = .0007), aGVHD grade III-IV (RR, 0.44; 95% CI, 0.30 to 0.64; P < .0001), and gut aGVHD (RR, 0.44; 95% CI, 0.30 to 0.66; P < .0001) were lower in the EN group than in the PN group. No differences were found between the 2 groups with regard to the incidence of severe oral mucositis (RR, 0.95; 95% CI, 0.83 to 1.09; P = .46) or overall survival at day +100 (RR, 1.07; 95% CI, 0.95 to 1.21; P = .29). Other variables were too heterogeneous to perform quantitative analyses. The results of the meta-analysis showed that EN reduced the incidence of aGVHD, specifically grade III-IV and gut aGVHD. This result should prompt improved efforts to implement EN as first-line nutritional support in patients undergoing allo-HSCT. Considering the emerging evidence regarding the association between GM dysbiosis and aGVHD onset, we speculate that this protective effect could be attributed to the improved gut eubiosis observed in enterally fed patients. Further studies are warranted to better address the relationship between the GM composition, aGVHD, and the nutritional administration route during HSCT.
异基因造血干细胞移植（allo-HSCT）患者的营养支持一直存在广泛争议。主要国际指南推荐肠内营养（EN）作为一线营养支持。然而，这些建议的证据基础薄弱，而且移植中心之间的营养支持类型存在很大差异，大多数中心提供肠外营养（PN）而不是 EN。本文提供了一项关于 allo-HSCT 后中性粒细胞减少期 EN 与 PN 比较的最新系统评价和荟萃分析。文献检索策略确定了 13 篇论文，其中 10 篇比较了临床移植结果，2 篇比较了肠道微生物群（GM）组成，1 篇比较了全身代谢谱。对于荟萃分析，在 10 项临床研究中，选择了 8 项比较 2 组的研究：在 1 组中，EN 作为 allo-HSCT 后中性粒细胞减少期的主要营养支持，可加用或不加用 PN（EN 组），而在另 1 组中，仅使用 PN 作为营养支持。EN 组急性移植物抗宿主病（aGVHD）的发生率（相对风险 [RR]，0.69；95%置信区间 [CI]，0.56 至 0.86；P =.0007）、aGVHD 3-4 级（RR，0.44；95%CI，0.30 至 0.64；P <.0001）和肠道 aGVHD（RR，0.44；95%CI，0.30 至 0.66；P <.0001）均低于 PN 组。两组之间严重口腔黏膜炎（RR，0.95；95%CI，0.83 至 1.09；P =.46）或第 100 天总生存率（RR，1.07；95%CI，0.95 至 1.21；P =.29）无差异。其他变量的异质性太大，无法进行定量分析。荟萃分析结果表明，EN 降低了 aGVHD 的发生率，特别是 3-4 级和肠道 aGVHD。这一结果应促使我们努力将 EN 作为 allo-HSCT 患者的一线营养支持。考虑到 GM 失调与 aGVHD 发病之间关联的新证据，我们推测这种保护作用可能归因于接受肠内喂养的患者中观察到的肠道微生物群组成的改善。需要进一步的研究来更好地解决 GM 组成、aGVHD 和 HSCT 期间营养管理途径之间的关系。
