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Time and residual hematopoiesis are crucial for PNH clones escape in hepatitis-associated aplastic anemia

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Abstract

The presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in aplastic anemia (AA) suggests immunopathogenesis, but when and how PNH clones emerge and proliferate are unclear. Hepatitis-associated aplastic anemia (HAAA) is a special variant of AA, contrarily to idiopathic AA, in HAAA the trigger for immune activation is clearer and represented by the hepatitis and thus serves as a good model for studying PNH clones. Ninety HAAA patients were enrolled, including 61 males and 29 females (median age 21 years). Four hundred three of idiopathic AA have been included as controls. The median time from hepatitis to cytopenia was 50 days (range 0–180 days) and from cytopenia to AA diagnosis was 26 days (range 2–370 days). PNH clones were detected in 8 HAAA patients (8.9%) at diagnosis and in 73 patients with idiopathic AA (IAA) (18.1%). PNH cells accounted for 4.2% (1.09–12.33%) of red cells and/or granulocytes and were more likely to be detected in patients with longer disease history and less severe disease. During follow-up, the cumulative incidence of PNH clones in HAAA increased to 18.9% (17/90). Nine HAAA patients newly developed PNH clones, including six immunosuppressive therapy (IST) nonresponders. The clone size was mostly stable during follow-up, and only 2 of 14 patients showed increased clone size without proof of hemolysis. In conclusion, PNH clones were infrequent in newly diagnosed HAAA, but their frequency increased to one that was similar to the IAA frequency during follow-up. These results suggest that the PNH clone selection/expansion process is dynamic and takes time to establish, confirming that retesting for PNH clones during follow-up is crucial.

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Funding

This study was supported by Grant 2017ZX09304024 of the National Science and Technology Major Project, by Grant 3332019094 of the Special Research Fund for Central Universities, Peking Union Medical College and by Grant 18JCYBJC41200 of Tianjin Manicipal Science and Technology Commission Grant.

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Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, Department of Anemia Therapeutic Center, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Wenrui Yang, Xin Zhao, Guangxin Peng, Li Zhang, Liping Jing, Kang Zhou, Yang Li, Lei Ye, Yuan Li, Jianping Li, Huihui Fan, Yang Yang & Fengkui Zhang

Authors
  1. Wenrui Yang
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  2. Xin Zhao
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  3. Guangxin Peng
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  4. Li Zhang
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  5. Liping Jing
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  6. Kang Zhou
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  7. Yang Li
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  8. Lei Ye
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  9. Yuan Li
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  10. Jianping Li
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  11. Huihui Fan
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  12. Yang Yang
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  13. Fengkui Zhang
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Contributions

FZ served as the principal investigator for this study. WY wrote the paper and contributed to patient recruitment and statistical analysis. XZ, GP, LZ, LJ, KZ, YL, LY, YL, JL, HF, and YY contributed to patient recruitment and treatment.

Corresponding author

Correspondence to Fengkui Zhang.

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This study was approved by the ethics committee of Blood Diseases Hospital, CAMS, and PUMC. All procedures followed were in accordance with the Helsinki Declaration of 1975, as revised in 2008. Patients provided written informed consent for data exploitation.

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The authors declare no competing interests.

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Yang, W., Zhao, X., Peng, G. et al. Time and residual hematopoiesis are crucial for PNH clones escape in hepatitis-associated aplastic anemia. Ann Hematol 100, 2435–2441 (2021). https://doi.org/10.1007/s00277-021-04553-5

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  • DOI: https://doi.org/10.1007/s00277-021-04553-5

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