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690 Parvovirus B19 Originates from Infected Hematopoietic Stem Cells Following Hematopoietic Stem Cell Transplantation

Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Risk Adapted Approaches to Reduce Transplant Related Toxicities
Hematology Disease Topics & Pathways:
Viral, Diseases, Infectious Diseases, Adverse Events
Sunday, December 8, 2024: 5:45 PM

Xuying Pei, PhD1, Xiaojun Huang2, Zhuojun Liu3*, Qiang Fu4*, Xiaosu Zhao5* and Yuqian Sun6*

1Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
2Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
3Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China
4Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease,Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
5Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China
6National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

Background: Human parvovirus B19 (B19) can lead to severe refractory anemia, aplastic crisis, and systemic lethal syndromes due to persistent infection of erythroid progenitor cells after hematopoietic stem cell transplantation (HSCT), however, the causes of pancytopenia have not yet demonstrated. Previous studies on post-transplant B19 infection have mainly been case reports, leaving its clinical characteristics and pathogenesis largely unexplored.

Methods: We examined the clinical manifestations, risk factors, and prognosis of 136 adult patients infected with B19 at our institution from 2017 to 2023. A control group of 408 patients without B19 infection was selected using propensity score matching. Single cell full-length RNA sequence (scFAST-seq) of four B19-infected patients and four B19-negative patients after HSCT were adopted to profile B19-infected cell spectrum and functional characteristics. Polymerase chain reaction (PCR) were performed to validate scFAST-seq results.

Results: Our study revealed a 2.6% incidence of B19 DNA viremia after allo-HSCT, with a median onset of 94 days post-transplant. Severe anemia, granulocytopenia, and thrombocytopenia were observed in 69.1%, 80.9%, and 96.3% of B19-positive patients, respectively. Persistent B19 infection, defined as B19 DNAemia lasting for 28 days or more occurred in 48 patients, often accompanied by severe pancytopenia (97.9%) and organ complications (54.1%). Importantly, B19 infection significantly correlated with poorer transplant outcomes, evidenced by higher non-relapse mortality and lower overall survival at 1, 3, and 5 years compared to the control group. Based on scFAST-seq data, we found that in adition to erythroid-lineage cells, which are well-known targets of B19, this virus could infect a broad spectrum of the hematopoietic system, including giant bone marrow myeloid and lymphoid-lineage cells, and even hematopoietic stem cells (HSCs). Interestingly, the scFAST-seq data showed a dramatic decrease in hematopoietic stem cells in patients infected with B19, which suggest that B19 may impair the survival of HSCs, potentially leading to pancytopenia. Moreover, B19-infected HSCs exhibited a higher expression levels of differentiation pathways toward downstream lineages, which may suggest that B19 disease originates from the infected HSCs.

Conclusion: This study provides a comprehensive clinical overview of B19 infection following HSCT and indicates poorer transplant outcomes in patients with B19 infection. Importantly, our findings suggest that B19 can infect a broad spectrum of the hematopoietic system post-HSCT, potentially originating from infected hematopoietic stem cells in patients with persistent B19 infection.

Disclosures: No relevant conflicts of interest to declare.

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