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

Linlin Jin,Jiang Zhu,Yonggang Zhou,Haiming Wei,Xiaohu Zheng,Huilan Liu,Zimin Sun,Xiaoyu Zhu,Kaidi Song,Baolin Tang,Binqing Fu,Yun Wu,Zhigang Tian,Rui Sun

doi:10.1038/s41467-021-24412-1

Linlin Jin, Jiang Zhu + Show 12 more

Open Access

https://doi.org/10.1038/s41467-021-24412-1

Copy DOI

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.

Highlights

Unrelated cord blood transplantation (UCBT) is an effective treatment for hematopoietic disorders
The incidence of relapse is lower in UCBT compared with Hematopoietic stem cell transplantation (HSCT) with a human leukocyte antigen (HLA)-matched or HLA-mismatched unrelated donor, indicating that CB may have a stronger graft versus leukemia (GVL) than bone marrow and peripheral blood stem cells (PBSC)[2,10]
Since the year 2000, a total of 1545 hematopoietic stem cell transplantations have been performed for the treatment of high-risk hematological disorders at the First Affiliated Hospital of the University of Science and Technology of China: 21 received bone marrow, 198 received bone marrow and PBSCs, 385 received PBSCs, and 941 received unrelated CB

Summary

Introduction

Unrelated cord blood transplantation (UCBT) is an effective treatment for hematopoietic disorders. 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. The study 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. The incidence of relapse is lower in UCBT compared with HSCT with a HLA-matched or HLA-mismatched unrelated donor, indicating that CB may have a stronger graft versus leukemia (GVL) than bone marrow and peripheral blood stem cells (PBSC)[2,10]. Since the success of UCBT is limited by mortality associated with severe PES, it is imperative to develop methods with which to control such toxicity and reduce mortality

Methods

Results

Conclusion