Ineffective Corticosteroid Treatment for Hemolysis Management of Paroxysmal Nocturnal Hemoglobinuria

Abstract Background: The primary clinical manifestations of paroxysmal nocturnal hemoglobinuria (PNH) are hemolytic anemia, bone marrow failure (BMF), and thromboembolism (TE). For optimum management, the contribution of both hemolysis and BMF to the complex anemia of PNH should be determined. The treatment of a hemolytic episode should aim at diminishing hemolysis and preventing complications. Corticosteroids as treatment, for both chronic hemolysis and acute hemolytic exacerbations have been used with a variety of side effects of long term use. In the Korean PNH population, corticosteroid (77.4%) represented the most common supportive care which provided with patients who had a history of corticosteroid use during the disease course (Lee JW et al. IJH. 2013 Jun; 97:749-57). There are no experimental data that provide a plausible explanation for why steroids should ameliorate the hemolysis of PNH. Aims: To evaluate the role of corticosteroid for treating chronic hemolysis in patients with PNH enrolled in the Korean prospective PNH registry. Methods: Korean patients with a diagnosis of PNH are eligible for inclusion in the prospective registry study designed to identify disease burden of PNH. Patient medical information data and other laboratory parameters were collected at the last 6 month follow-up.Here we analyzed patients with corticosteroid use within the past 6 months. 97 patients who were followed up at least 6 months after study enrollment was categorized into two groups. Patients have received eculizumab treatment or bone marrow transplantation (BMT) during the last 6month of follow up was excluded. Results: Among the 97 patients, 23% (22 patients) had corticosteroid therapy in the past 6 months. Mean age was 46 years (range 20-87; standard deviation, 16.3) and 51 patients (53 %) were female. At the time of analysis, 74 of 97 patients had recorded lactate dehydrogenase (LDH) levels. The mean LDH at 6months follow up after enrollment was 4.75-fold above the upper limit of normal (ULN) of the patients with corticosteroid use and 4.16-fold above ULN was reported in patients without corticosteroid use for the past 6 months (p=0.446). Hemolysis (LDH≥1.5 x ULN) was reported in 86% of patients with corticosteroid use and 77% of patients without corticosteroid use; there was no statistically significant difference between these two patient populations (p=0.420). The mean granulocyte clone size at enrollment in patients with corticosteroid use was 50.7% (range 1-98) and patients without corticosteroid use reported 52.3% (range 1-99) (p=0.850). The mean reticulocyte percent between two groups was 4.87% and 4.0%, respectively (p=0.317). Red blood cell was transfused to 15 (68.1%) of the 22 patients with corticosteroid use and 23 (30.7.%) of patients without corticosteroid use during the last 6 month follow-up; there was a significant difference between the two groups for mean unit of transfusion (p=0.005) (Table1). There was no new thromboembolism event reported during the past 6 months. Each group experienced abdominal pain and dyspnea during the last 6 months of follow up: patients with corticosteroid use vs. patients without corticosteroid use (p=0.121 and p= 0.055, respectively) (Table1). Conclusions: In the past, the main value of corticosteroids may have been to treat chronic hemolysis although it is limited by toxicity and the harm that can accrue from long term use. However, our results demonstrated that the management of hemolysis of PNH with corticosteroid could be ineffective and unsatisfactory. These data confirm that PNH patients with corticosteroid had ineffective hemolysis management (LDH ≥1.5 x ULN) and also suffer from disabling clinical signs and symptoms, such as continuous transfusion requirement with anemia, abdominal pain and dyspnea. Awareness of the potentially debilitating effects of corticosteroid myopathy and sensitivity to the disfiguring consequences of long term use are essential for proper management and also careful follow-up should be recommended. [Table 1] Total (N=97) Patients with corticosteroid use (n=22) Patients without corticosteroid use (n=75) p -value LDH fold above ULN (n=74), Mean (SD) Hemolysis (LDH ≥ 1.5xULN), n (%) 4.75 fold (3.02) 18/21 (85.7) 4.16 fold (2.89) 41/53 (77.4) 0.446 0.420 Transfusion (n=38), Mean unit (SD) 6.1 (9.43) 2.0 (3.99) 0.005 Abdominal pain (n=16) , n (%) 6/22 (27.3) 10/75 (11.2) 0.121 Dyspnea (n=11) , n (%) 5/22 (22.7) 6/75 (8.0) 0.055 Disclosures Lee: Alexion Pharmaceuticals: Consultancy. Jang:Alexion Pharmaceuticals: Consultancy. Lee:Alexion Pharmaceuticals: Consultancy. Jo:Alexion Pharmaceuticals: Consultancy. Kim:Alexion Pharmaceuticals: Consultancy.