Background  Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disease. Currently, the treatment of PNH is simple and expensive. Therefore, it is urgent to find new treatment drugs or programs that can significantly improve the efficacy and quality of life of patients.

  Objective  To evaluate the efficacy and safety of all-trans retinoic acid combined with androgen and glucocorticoid in the treatment of PNH.

  Methods  PNH patients who met the inclusion criteria and were admitted to Chinese PLA General Hospital from December 2019 to August 2021 were selected for the trial. The enrolled patients were treated with all-trans retinoic acid 10mg/d for 12 weeks in addition to the original glucocorticoid and androgen therapy. The intravascular hemolysis, incidence of thrombosis, proportion of PNH type Ⅲ red blood cells, proportion of CD59/FLAER expression deficient granulocytes, hemoglobin concentration, reticulocyte count were observed. The safety assessment included the incidence of adverse events and liver and kidney function assessment.

  Results  A total of 6 patients, 3 males and 3 females with age from 31 to 55 years old, were included in the 12-week treatment. The median proportion of type Ⅲ red blood cells was 50.31% (9.73%, 55.38%), and the proportion of granulocytes with CD59 and FLAER expression deficiency was 43.23% ± 29.75%. Of the 6 cases, 4 patients had aplastic anemia, 2 patients had a clear history of thrombosis, and 4 patients had a history of transfusion dependence. After 12 weeks of treatment, all patients had stopped blood transfusion, and the hemoglobin concentration of patients increased significantly (97.33 ± 33.18 g/L vs 81.00 ± 28.01 g/L), while the proportion of reticulocytes decreased, but the difference was not statistically significant. In terms of PNH clonal protection, a total of 5 patients completed evaluation after 12 weeks of treatment, of which two patients had significant response. There was no new thrombosis in all patients during the treatment, and the main adverse reaction in treatment were the increase of glutamic pyruvic transaminase and aspartate aminotransferase.

  Conclusion  Preliminary observation shows that the combined regimen containing all-trans retinoic acid is effective with low toxicities in the treatment of paroxysmal nocturnal hemoglobinuria, but needs further large scale clinical trial.