Pb2067: prospective self-control analysis of glucocorticoid maintenance therapy for paroxysmal nocturnal hemoglobinuria

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, complement-mediated hemolytic anemia resulting from a somatic phosphatidylinositol glycan class A (PIGA) mutation on the X chromosome of hematopoietic stem cells. PNH mainly presents as hemolytic anemia, bone marrow failure, and thrombosis. Targeting the terminal complement inhibitor, such as eculizumab, could not only controls hemolytic anemia, thrombosis and transfusion, and prevents the deterioration of renal function in PNH patients. However, eculizumab has not yet entered China market, glucocorticoid is still used for the first-line treatment in China. Due to the rarity of PNH patients, there currently lack systematic studies evaluating the long-term effects of glucocorticoids. Aims: The purpose is to identify the efficacy of glucocorticoid maintenance therapy in PNH. Methods: This prospective study was conducted by the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100050945) from September 2020 to April 2022, including three centers: Jiangsu Province Hospital, Jiangning Hospital, the Second Hospital of Nanjing. 26 PNH patients with high disease activity (HAD), which means an increase in lactate dehydrogenase (LDH) ≥ 1.5 times the upper limit of normal (ULN), with at least one of the following signs or symptoms: fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia with hemoglobin (Hb) < 100 g/L), major vascular adverse events (including thromboembolic events), dysphagia, or erectile dysfunction, were enrolled in the study (Table 1). Oral prednisone was initiated at a dose of 1mg/kg/day and gradually reduced to discontinuation after four weeks. Clinical characteristics before treatment, and 1st, 3rd, and 6th after treatment were compared. Results: The level of hemoglobin was improved at 1st month, and stable at 3rd month, and 6th month: (69.12±14.83) vs (77.50±18.11), p＜0.05；(69.12±14.83) vs (74.15±18.23), p=0.15；(69.12±14.83) vs (75.54±19.91), p=0.09; but the stratification of anemia (>90g/L, 60-90g/L, <60g/L) showed no difference: p=0.082, p=0.344, p=0.247; the reticulocyte percentage also had no difference: (6.76±3.92) vs (6.23±4.08) vs (6.62±3.92) vs (7.11±4.73), p=0.457. 25 patients (25/26, 96.15%) required blood transfusion before treatment, and there were 19 patients (19/26, 73.08%), 22 patients (22/26, 84.62%), 21 patients (21/26, 80.77%) were transfusion dependent at 1st, 3rd, and 6th months. No marked changes happened in the proportion of patients with transfusion dependent (p=0.031; p=0.375; p=0.219) at each time points, and there was an additional patient with transfusion dependent at three time points. No one achieved hemolysis control (LDH < 1.5 ⅹULN), and no marked improvement were achieved in lactate dehydrogenase and indirect bilirubin (p=0.436, p=0.881). Before treatment, level of D-dimer elevated (>0.55mg/L) in 7 patients, and in 6 patients, 5 patients, 7 patients, respectively at 1st, 3rd, and 6th months, and no marked improvement of D-dimer were achieved (p=0.263). Before treatment, 1 patient suffered renal insufficiency, and there was an additional patient with renal function deterioration at three time point of 1st, 3rd, and 6th months, respectively. Glomerular filtration rate before treatment was (114.15±42.98) ml/min/1.73m2, it was (117.79±37.69) ml/min/1.73m2, (120.85±44.05) ml/min/1.73m2, (110.30±36.58) ml/min/1.73m2 at 1st, 3rd, and 6th months respectively, and was similar (p=0.42, p=0.43, p=0.41). Summary/Conclusion: It was preliminarily showed that prednisone maintenance therapy for PNH could not control hemolysis, improve anemia, thrombosis and renal function. Long-term glucocorticoid maintenance therapy for PNH was not recommend.Keywords: Paroxysmal nocturnal hemoglobinuria (PNH), Hemolysis, Therapy, Anemia