Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation

被引：26

作者：

Shouval, Roni ^{[1
,2
]}

Waters, Nicholas R. ^{[3
]}

Gomes, Antonio L. C. ^{[3
]}

Brambilla, Corrado Zuanelli ^{[1
,4
,5
]}

Fei, Teng ^{[6
]}

Devlin, Sean M. ^{[6
]}

Nguyen, Chi L. ^{[3
]}

Markey, Kate A. ^{[1
,7
]}

Dai, Anqi ^{[3
]}

Slingerland, John B. ^{[3
]}

Clurman, Annelie G. ^{[3
]}

Fontana, Emily ^{[8
]}

Amoretti, Luigi A. ^{[8
]}

Wright, Roberta J. ^{[8
]}

Hohl, Tobias M. ^{[2
,8
]}

Taur, Ying ^{[2
,8
]}

Sung, Anthony D. ^{[9
]}

Weber, Daniela ^{[10
]}

Hashimoto, Daigo ^{[11
]}

Teshima, Takanori ^{[11
]}

Chao, Nelson J. ^{[9
]}

Holler, Ernst ^{[10
]}

Scordo, Michael ^{[1
,2
]}

Giralt, Sergio A. ^{[1
,2
]}

Perales, Miguel-Angel ^{[1
,2
]}

Peled, Jonathan U. ^{[1
,2
,12
]}

van den Brink, Marcel R. M. ^{[1
,2
,3
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, New York, NY 10065 USA

[2] Weill Cornell Med Coll, Dept Med, New York, NY USA

[3] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Immunol, New York, NY 10065 USA

[4] Univ Siena, Dept Med Biotechnolo gies, Siena, Italy

[5] Azienda Ospedaliera Univ Senese, Dept Oncol, Hematol Unit, Siena, Italy

[6] Mem Sloan Kettering Canc Ctr, Depart ment Epidemiol & Biostat, New York, NY 10065 USA

[7] Fred Hutchinson Canc Res Ctr, Seattle, WA USA

[8] Mem Sloan Kettering Canc Ctr, Dept Med, Infect Dis Serv, New York, NY 10065 USA

[9] Duke Univ, Med Ctr, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC USA

[10] Univ Regensburg, Univ Med Ctr, Dept Internal Med, Regensburg, Germany

[11] Hokkaido Univ, Fac Med, Dept Hematol, Sapporo, Japan

[12] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA

来源：

CLINICAL CANCER RESEARCH | 2023年 / 29卷 / 01期

关键词：

VERSUS-HOST-DISEASE; DIVERSITY;

D O I：

10.1158/1078-0432.CCR-22-1254

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: The gut microbiota is subject to multiple insults in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. We hypothesized that preparative conditioning regi-mens contribute to microbiota perturbation in allo-HCT.Experimental Design: This was a retrospective study that eval-uated the relationship between conditioning regimens exposure in 1,188 allo-HCT recipients and the gut microbiome. Stool samples collected from 20 days before transplantation up to 30 days after were profiled using 16S rRNA sequencing. Microbiota injury was quantified by changes in a-diversity.Results: We identified distinct patterns of microbiota injury that varied by conditioning regimen. Diversity loss was graded into three levels of conditioning-associated microbiota injury (CMBI) in a multivariable model that included antibiotic exposures. High -intensity regimens, such as total body irradiation (TBI)-thiotepa-cyclophosphamide, were associated with the greatest injury (CMBI III). In contrast, the nonmyeloablative regimen fludarabine- cyclophosphamide with low-dose TBI (Flu/Cy/TBI200) had a low-grade injury (CMBI I). The risk of acute GVHD correlated with CMBI degree. Pretransplant microbial compositions were best preserved with Flu/Cy/TBI200, whereas other regimens were associated with loss of commensal bacteria and expansion of Enterococcus.Conclusions: Our findings support an interaction between con-ditioning at the regimen level and the extent of microbiota injury.

引用

页码：165 / 173

页数：9

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