Nature sub-Journal Wei Haiming/Tian Zhigang of University of Science and Technology of China reveals that tocilizumab can potentially treat preimplantation syndrome

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iNature unrelated cord blood transplantation (UCBT) is an effective method for the treatment of hematopoietic diseases
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However, this attractive method is often accompanied by preimplantation syndrome (PES).
Severe cases of PES are associated with increased mortality and morbidity, but the pathogenesis of PES is unclear
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On July 6, 2021, Wei Haiming, Tian Zhigang and Sun Zimin of the University of Science and Technology of China jointly published a research paper entitled "Inflammatory monocytes promote pre-engraftment syndrome and tocilizumab can therapeutically limit pathology in patients" in Nature Communications.
The research shows GM-CSF produced by cord blood-derived inflammatory monocytes drives PES pathology, and monocytes are the main source of IL-6 during PES
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In addition, the study reports the results of a single-arm, single-center clinical study of tocilizumab in patients with steroid-refractory severe PES
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The study was in line with the main outcome indicator because there were no non-recurrent deaths during the 100-day follow-up period
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The study also met the key secondary outcome indicators for neutrophil engraftment and hematopoiesis
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These findings provide a therapeutic strategy to address PES and improve non-relapse mortality
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Hematopoietic stem cell transplantation (HSCT) is an effective treatment for hematological malignancies (leukemia, myeloma, and lymphoma) and other hematological diseases (myelodysplastic and aplastic anemia
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However, given the polymorphism of human leukocyte antigen (HLA) With a wide range of sex and the small size of modern families, most patients who require HSCT do not have an HLA-matched donor
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HLA-Haploidentical transplantation is spreading rapidly around the world, and cord blood (CB) is also a good alternative source of hematopoietic stem cells
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CB As a source of stem cells, it has many advantages
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For example, CB is more tolerant of HLA differences due to its lower immunogenicity
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When urgent HSCT is needed, it can also be provided immediately
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Crucially, CB is very easy to buy, and it is very good for newborns.
There is no risk
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Increasing evidence shows that for patients who lack relevant and HLA-matched unrelated donors, haploid identical donors and CB are promising options
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Although hematopoietic recovery is delayed, unrelated cord blood transplantation (UCBT) recipients have a lower incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD)
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In addition, UCBT has a lower recurrence rate compared with HSCT of HLA-matched or HLA-mismatched unrelated donors, indicating that CB may have stronger graft resistance to leukemia (GVL) than bone marrow and peripheral blood stem cells (PBSC)
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Unfortunately, UCBT is usually accompanied by the emergence of unique early immune responses that occur before neutrophil implantation.
These early immune responses are called "preimplantation syndrome" (PES)
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PES is common after UCBT and is characterized by non-infectious high fever, skin rash, diarrhea, and other clinical manifestations, including lung infiltration or weight gain
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PES occurs within the first few days after UCBT; the onset of symptoms usually occurs from 5 days to occasionally 11 days after cord blood transfusion
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According to reports, the incidence of PES after UCBT is 20% to 86.
8%
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However, the only treatment available for PES is corticosteroids
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In contrast, some severe PES patients are refractory to steroids
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Since the success of UCBT is limited by the mortality associated with severe PES, methods must be developed to control this toxicity and thereby reduce mortality
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Unfortunately, the pathogenesis of PES is still unclear
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PES has also appeared in patients who have never achieved transplantation, which suggests that PES may be a response to the infusion of cord blood
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It is known that plasma C-reactive protein (CRP) levels increase slightly at the beginning of PES
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Since CRP is a non-specific marker of inflammation, these findings may indicate that inflammation plays a key role in PES
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It is known that monocytes are sensitive to GM-CSF
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However, whether the expression profile of GM-CSF and umbilical cord blood-derived monocytes are related to the inflammatory response observed during PES remains to be studied
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In this work, mononuclear cells derived from peripheral blood stem cells and umbilical cord blood were comprehensively studied
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This study provides evidence that monocytes derived from cord blood have inflammatory characteristics
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In addition, monocytes are involved in the pathogenesis of PES and represent the main source of IL-6 during PES
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Importantly, the results of this study provide a treatment strategy for patients with steroid-refractory PES
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