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Successful use of defibrotide to treat allogeneic hematopoietic stem cell transplantation associated thrombotic microangiopathy in pediatric patients: report from Chinese single center

Bone Marrow Transplantation volume 59, pages 1483–1485 (2024)Cite this article

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Transplantation-associated thrombotic microangiopathy (TA-TMA) is a syndrome of endothelial injury that is a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The main clinical features are microvascular hemolytic anemia, thrombocytopenia, microvascular thrombosis, and multiple organ dysfunction [1, 2], and its incidence varies from 3 to 39% [3,4,5]. Because the clinical manifestations may overlap with those of other common posttransplant complications, TA-TMA is highly susceptible to misdiagnosis or missed diagnosis, and early diagnosis and treatment are difficult. However, patients with TA-TMA have high treatment-related mortality (TRM) [6,7,8], making the treatment of this disease critical. Defibrotide can stabilize and protect endothelial cells, has antithrombotic and thrombolytic effects, and is considered a very promising drug for the treatment of TA-TMA. Our study retrospectively analyzed the clinical characteristics and therapeutic effects of defibrotide in children with single-center TMA and demonstrated favorable responses. To our knowledge this is the first report on defibrotide therapy for TA-TMA treatment in China.

We retrospectively analyzed the clinical data of children who underwent allo-HSCT at the Hematology Oncology Center of Beijing Children’s Hospital from January 2018 to December 2021, including 36 patients with TA-TMA. Our patient population included patients with nonmalignant diseases such as aplastic anemia, osteopetrosis, chronic active EBV infection, and EBV-related hemophagocytic lymphohistiocytosis or malignant diseases such as acute leukemia, non-Hodgkin lymphoma and so on. The majority of haploidentical transplantations were performed with in vivo T-cell depletion, which contributes to the relatively high incidence of TMA. Our hospital referred to the expert consensus proposed by Chinese Medical Association for TA-TMA diagnosis [9]. The glomerular filtration rate calculated according to age, height and creatinine was used to evaluate renal involvement; neuropsychiatric symptoms, signs and imaging findings were used to evaluate the degree of central nervous system damage; and intestinal TMA was judged by abdominal pain, diarrhoea, and gastrointestinal bleeding, after excluding infection. For the children treated with defibrotide, the indices before diagnosis were collected from records. The standard dose of 6.25 mg/kg defibrotide q6h mainly refers to the treatment of VOD after transplantation in children. Treatment is effective if the child’s hemoglobin (HGB), platelet (PLT), lactate dehydrogenase (LDH), blood creatinine levels, and psychiatric symptoms gradually return to their pre-diagnostic state after treatment; treatment is ineffective if HGB and PLT decrease progressively, LDH and blood creatinine levels increase, and the disease continues to progress [10]. Follow-up until October 2022. The median follow-up time was 18 (0–49) months. All surviving children were followed up for more than 1 month.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 82370142) and the Beijing Municipal Natural Science Foundation (No.7232130).

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Author notes

  1. These authors contributed equally: Jiayu Wang, Yanhui Luo, Chenguang Jia.

  2. These authors jointly supervised this work: Guanghua Zhu, Maoquan Qin, Sidan Li.

Authors and Affiliations

  1. Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

    Jiayu Wang, Yanhui Luo, Chenguang Jia, Jun Yang, Bin Wang, Jie Zheng, Yuanfang Jing, Wei Chen, Wei Yang, Guanghua Zhu & Maoquan Qin

  2. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Sidan Li

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  1. Jiayu Wang
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Contributions

Jiayu Wang, Yanhui Luo and Chenguang Jia: Conceptualization, Methodology, Formal analysis, Writing-Original Draft. Jun Yang, Bin Wang, Jie Zheng, Yuanfang Jing, Wei Chen, Wei Yang: Data Curation, Conceptualization, Validation, Writing-Review and Editing. Guanghua Zhu, Maoquan Qin and Sidan Li: Writing-Review and Editing, Supervision.

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Correspondence to Guanghua Zhu, Maoquan Qin or Sidan Li.

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Wang, J., Luo, Y., Jia, C. et al. Successful use of defibrotide to treat allogeneic hematopoietic stem cell transplantation associated thrombotic microangiopathy in pediatric patients: report from Chinese single center. Bone Marrow Transplant 59, 1483–1485 (2024). https://doi.org/10.1038/s41409-024-02368-2

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