A team led by Prof. WEI Haiming and Prof. TIAN Zhigang from University of Science and Technology of China (USTC), collaborating with Prof. SUN Zimin's team from the First Affiliated Hospital of USTC, revealed the pathological mechanism of severe pre-engraftment syndrome (PES) after umbilical cord blood transplantation. The study, published in Nature communications on July 6, provides a treatment strategy and helps the improvement in the curative effect of unrelated cord blood transplantation (UCBT).

UCBT is an important means to cure hematological malignancies, hematopoietic failure, congenital immunodeficiency and some genetic metabolic diseases. The First Affiliated Hospital has so far completed 1519 cases of UCBT since its first successful case in the treatment of children's malignant hematological diseases in 2000. The symptoms of chronic graft-versus-host disease (GVHD) after transplantation are mild.

In the early stage after UCBT, 70-80% of recipients will suffer PES, which is characterized by high fever, rash, diarrhea, etc., and severe PES increases the transplant-related mortality. However, the mechanism of the pathogenesis of PES after UCBT is still unclear. The research on this mechanism is of great significance for the treatment of PES patients.

Diagram of cytokine dysregulation in PES. (Image by JIN Linlin et al.)

  The researchers in this study analyzed the peripheral blood of recipients after UCBT and found a sharp increase in the number of monocytes in PES patients. These monocytes derived from cord blood had inflammatory characteristics and produced proinflammatory cytokines such as GM-CSF and IL-6. After UCBT, monocytes expanded rapidly in the recipient body, increasing the levels of GM-CSF and IL-6 in serum, leading to the occurrence of PES.

Based on the pathogenesis study of PES, the researchers applied for a clinical trial using tocilizumab to block the IL-6 receptor at www.chictr.org.cn (Reference: ChiCTR1800015472) among severe PES patients. The results showed that the use of tobuzumab for intervention treatment controls the clinical symptoms of PES and reduces the mortality of patients.

Paper link: https://www.nature.com/articles/s41467-021-24412-1

(Written by WENG Jingwen, edited by HOU Luyao, USTC News Center)