AbstractBacterial bloodstream infections (BSI) can be a substantial contributor to complications of GVHD treatment. The aim of this study was to determine the risk for BSI from neutrophil engraftment through day 100 post transplant in patients with acute GVHD (AGVHD) based on organ involvement and severity.

摘要细菌性血流感染（BSI）可能是GVHD治疗并发症的重要原因。这项研究的目的是根据器官受累和严重程度确定急性GVHD（AGVHD）患者中性粒细胞植入至移植后第100天的BSI风险。

Patients (n = 4064) who underwent an allogeneic hematopoietic stem cell transplant (HCT) reported to the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients and was associated with a greater day-100 incidence of post engraftment BSI than with grade 0/I (24.9 vs. 15.3%).

分析了向CIBMTR登记处报告的接受异基因造血干细胞移植（HCT）的患者（n=4064）。II-IV级AGVHD发生在1607例（39.5%）患者中，植入后BSI的100天发病率高于0/I级（24.9比15.3%）。

Patients with grade III/IV AGVHD had the highest BSI risk (HR 2.45; 95% CI 1.99–3.0; p < 0.0001). Lower GI involvement increased BSI risk (HR 1.54; 95% CI 1.17–2.02; p = 0.0019). BSI post-engraftment through day 100 was associated with worse survival (HR 1.64, 95% CI 1.43–1.87; p < 0.001) and higher non-relapse mortality (NRM), (HR 2.22; 95% CI 1.91–2.59; p < 0.001).

III/IV级AGVHD患者的BSI风险最高（HR 2.45；95%CI 1.99-3.0；p<0.0001）。较低的胃肠道受累增加了BSI风险（HR 1.54；95%CI 1.17-2.02；p=0.0019）。BSI植入后至第100天与较差的生存率（HR 1.64,95%CI 1.43-1.87；p<0.001）和较高的非复发死亡率（NRM）相关（HR 2.22,95%CI 1.91-2.59；p<0.001）。

Those with stage III/IV GI involvement are at highest risk for BSI. Future studies evaluating novel methods for preventing BSI in these high risk populations are needed to reduce mortality associated with AGVHD.Highlights.

那些III/IV期胃肠道受累的患者患BSI的风险最高。需要进一步研究评估在这些高危人群中预防BSI的新方法，以降低与AGVHD相关的死亡率。。

Bacterial blood stream infections are more common in patients with Grade II-IV AGVHD with roughly 25% of these patients developing at least one BSI by day-100.

细菌性血流感染在II-IV级AGVHD患者中更为常见，其中约25%的患者在第100天至少发生一次BSI。

Patients with grade III/IV AGVHD and those with lower gastrointestinal involvement are at the highest risk for BSI.

III/IV级AGVHD患者和下消化道受累患者发生BSI的风险最高。

Patients who experience a BSI by day 100 have worse survival and over a two-fold higher probability for non-relapse mortality.

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The final analysis dataset will be posted to the CIBMTR website at: https://cibmtr.org/CIBMTR/Resources/Publicly-Available-Datasets#.

最终分析数据集将发布到CIBMTR网站：https://cibmtr.org/CIBMTR/Resources/Publicly-Available-Datasets#.

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Download referencesFundingThe CIBMTR is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); N00014-23-1-2057 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, Gateway for Cancer Research, Pediatric Transplantation and Cellular Therapy Consortium and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Alexion; Allogene; AlloVir, Inc.; Amgen, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; BioLineRX; Blue Spark Technologies; bluebird bio, inc.; Blueprint Medicines; Bristol Myers Squibb Co.; CareDx Inc.; CSL Behring; CytoSen Therapeutics, Inc.; DKMS; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; Gift of Life Biologics; Gift of Life Marrow Registry; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karius; Kashi Clinical Laboratories; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Labcorp; Legend Biotech; Mallinckrodt Pharmaceuticals; Med Learning Group; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miller Pharmacal Group, Inc.; Miltenyi Biotec, Inc.; MorphoSys; MSA-EDITLife; Neovii Pharmaceuticals AG; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, Inc.; OriGen BioMedical; Ossium .

下载参考文献资助CIBMTR主要由国家癌症研究所（NCI），国家心肺血液研究所（NHLBI）和国家过敏与传染病研究所（NIAID）的公共卫生服务U24CA076518支持；来自卫生资源和服务管理局（HRSA）的75R60222C00011；海军研究办公室的N00014-23-1-2057；Be Match基金会，威斯康星州医学院，国家骨髓捐赠者计划，癌症研究门户，儿科移植和细胞治疗联盟以及以下商业实体也提供了支持：AbbVie；Actinium制药公司。；自适应生物技术公司；；Adienne SA；亚力兄；异基因；阿洛韦公司。；安进公司。；美国阿斯特拉斯制药公司；阿斯利康；阿塔拉生物疗法；贝金；BioLineRX；Blue Spark Technologies公司；蓝鸟生物公司。；蓝图药物；百时美施贵宝公司。；CareDx公司。；CSL贝林；CytoSen Therapeutics，Inc。；DKMS；Eurofins Viracor，DBA Eurofins移植诊断；。；生命礼物生物制品；生命礼物骨髓登记处；葛兰素史克；组织遗传学；Incyte公司；Iovance公司；杨森研究与发展有限责任公司；杨森/强生公司；Jasper Therapeutics；爵士制药公司。；卡里斯；喀什临床实验室；凯迪斯制药；基列德公司Kite；协和麒麟；Labcorp公司；联想生物技术；马林克罗特制药公司；医学学习小组；。；中胚层；千年，武田肿瘤公司。；米勒制药集团。；Miltenyi Biotec公司。；MorphoSys公司；MSA EDITLife；Neovii Pharmaceuticals AG；诺华制药公司；奥梅罗斯公司；OptumHealth；奥卡生物系统公司。；OriGen生物医学；骨化。

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Dr. C Lee reports advisory board participation for Sanofi, Kite, Kadmon, BMS, and Incyte; research funding from Incyte; steering board committee participation for Incyte; speakers panel participation for Kite; and consulting for Fresenius Kabi, Sanofi, and Mallinckrodt. Dr. Sharma reports Grant funds from CRISPR Therapeutics; Consulting fees from Spotlight Therapeutics, Medexus Inc., Vertex Pharmaceuticals, Sangamo Therapeutics and Editas Medicine; and is the St.

C Lee博士报告了赛诺菲，Kite，Kadmon，BMS和Incyte的咨询委员会参与情况；来自Incyte的研究资金；Incyte指导委员会的参与；风筝演讲者小组参与；并为费森尤斯·卡比（Fresenius Kabi）、赛诺菲（Sanofi）和马林克罗特（Mallinckrodt）提供咨询。Sharma博士报告了CRISPR Therapeutics的赠款；Spotlight Therapeutics，Medexus Inc.，Vertex Pharmaceuticals，Sangamo Therapeutics和Editas Medicine的咨询费；这是圣。

Jude Children’s Research Hospital site principal investigator of clinical trials for genome editing of sickle cell disease sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics (NCT03745287), Novartis Pharmaceuticals (NCT04443907) and Beam Therapeutics (NCT05456880). The industry sponsors provide funding for the clinical trial, which includes salary support paid to Dr.

裘德儿童研究医院现场镰状细胞病基因组编辑临床试验首席研究员，由Vertex Pharmaceuticals/CRISPR Therapeutics（NCT03745287），诺华制药（NCT04443907）和Beam Therapeutics（NCT05456880）赞助。行业赞助商为临床试验提供资金，其中包括支付给Dr。

Sharma’s institution. Dr. Sharma has no direct financial interest in these therapies. Dr. Nishihori reports significant payments (research support) to the institution for clinical trial (Novartis), research support (drug supply only) to the institution for clinical trial (Karyopharm) and advisory board participation for Medexus.

Sharma的机构。Sharma博士对这些疗法没有直接的经济利益。Nishihori博士向临床试验研究所（Novartis）报告了大量款项（研究支持），向临床试验研究所（Karyopharm）报告了研究支持（仅限药物供应），并报告了Medexus咨询委员会的参与情况。

Dr. Kitko reports compensation for ad board for Horizon Therapeutics and Incyte and compensation for participation in CME lectures about GVHD for Sanofi, Physicians Education Resource and i3Health. Dr. Pidala reports consulting and advisory board membership for Syndax, CTI Biopharma, Amgen, Regeneron, and Incyte; and clinical trial support for Novartis, Amgen, Takeda, Janssen, Johnson and Johnson, Pharmacyclics, Abbvie, CTI Biopharma, and BMS.

Kitko博士报告了Horizon Therapeutics和Incyte广告板的报酬，以及参加赛诺菲、医师教育资源和i3Health有关GVHD的CME讲座的报酬。Pidala博士报告了Syndax，CTI Biopharma，Amgen，Regeneron和Incyte的咨询和顾问委员会成员；以及诺华，安进，武田，杨森，强生，Pharmacyclics，Abbvie，CTI Biopharma和BMS的临床试验支持。

Dr. S Lee reports compensation (research funding) from Amgen, AstraZeneca, Incyte, Kadmon, Pfizer, Syndax; steering committee participation for Incyte; drug supply for Janssen; co.

S Lee博士报告了Amgen，AstraZeneca，Incyte，Kadmon，Pfizer，Syndax的报酬（研究资金）；Incyte指导委员会的参与；杨森的药物供应；公司。

Ethics approval and consent to participate

道德批准和同意参与

This study was approved the NMDP Institutional Review Board, registration number IRB00001253. All patients provided written informed consent for research participation and data submission, in accordance with the Declaration of Helsinki.

这项研究得到了NMDP机构审查委员会的批准，注册号为IRB00001253。根据赫尔辛基宣言，所有患者均提供了书面知情同意书，以参与研究和提交数据。

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et al. Incidence of bacterial blood stream infections in patients with acute GVHD..

急性GVHD患者细菌性血流感染的发生率。。

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