Inflammatory monocytes promote pre-engraftment syndrome and tocilizumab can therapeutically limit pathology in patients

Linlin Jin, Zimin Sun (), Huilan Liu, Xiaoyu Zhu, Yonggang Zhou, Binqing Fu, Xiaohu Zheng, Kaidi Song, Baolin Tang, Yun Wu, Jiang Zhu, Rui Sun, Zhigang Tian () and Haiming Wei ()
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Linlin Jin: University of Science and Technology of China
Zimin Sun: University of Science and Technology of China
Huilan Liu: University of Science and Technology of China
Xiaoyu Zhu: University of Science and Technology of China
Yonggang Zhou: University of Science and Technology of China
Binqing Fu: University of Science and Technology of China
Xiaohu Zheng: University of Science and Technology of China
Kaidi Song: University of Science and Technology of China
Baolin Tang: University of Science and Technology of China
Yun Wu: University of Science and Technology of China
Jiang Zhu: University of Science and Technology of China
Rui Sun: University of Science and Technology of China
Zhigang Tian: University of Science and Technology of China
Haiming Wei: University of Science and Technology of China

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Unrelated cord blood transplantation (UCBT) is an effective treatment for hematopoietic disorders. However, this attractive approach is frequently accompanied by pre-engraftment syndrome (PES), severe cases of PES are associated with enhanced mortality and morbidity, but the pathogenesis of PES remains unclear. Here we show that GM-CSF produced by cord blood-derived inflammatory monocytes drives PES pathology, and that monocytes are the main source of IL-6 during PES. Further, we report the outcome of a single arm, single-center clinical study of tocilizumab in the treatment of steroid-refractory severe PES patients (www.chictr.org.cn ChiCTR1800015472). The study met the primary outcome measure since none of the patients was nonrelapse death during the 100 days follow-up. The study also met key secondary outcomes measures of neutrophil engraftment and hematopoiesis. These findings offer a therapeutic strategy with which to tackle PES and improve nonrelapse mortality.

Date: 2021
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DOI: 10.1038/s41467-021-24412-1

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