Analysis of persistent anemia following Eculizumab treatment in paroxysmal nocturnal hemoglobinuria patients with high disease-activity status
ZHANG Ting
YUAN Ying-ying
QIN Cheng-tao
MA Yong-chao
GONG Yue-min
ZHANG Ya-wen
FANG Bao-zhi
LYU Ming-en
XU Jin-ge
SHI Xiao-feng
HE Guang-sheng
SHI Jin-ning
Abstract：Objective To investigate the factors contributing to persistent anemia in Chinese patients with high disease-activity paroxysmal nocturnal hemoglobinuria(PNH)undergoing Eculizumab therapy.Methods A prospective registry-based analysis was conducted on 33 high disease-activity PNH patients treated with Eculizumab for at least 6 months between December 2023 and December 2024 in the hospitals of Chinese Eastern Collaboration Group of Anemia,analyze the patient's condition and causes of persistent anemia.Results Among 33 patients,9 patients maintained Hb＞100 g/L(1 patient ≥120 g/L),and 24 patients exhibited Hb＜100 g/L.The incidence of comorbid aplastic anemia was lower in patients with Hb level of 10 or more(22％vs.67％,P=0.029).Anti-C3d positivity via direct antiglobulin test(DAT)was detected in 13 patients(13/33,39％),with median onset time of 12(2-32)weeks and median anti-C3d titer of 64(16-256).7 patients demonstrated C3d titers ≥1:64.At 6-month follow-up after eculizumab treatment,the median PNH clone size in type Ⅱ+Ⅲerythrocytes was 17.7％(1.8％-99.7％),which is lower than that in neutrophil clones.Twenty patients exhibited PNH size in type Ⅱ+Ⅲ erythrocyte were 10 percentage or lower by comparing to neutrophil,while 5 patients showed 5％-9％difference.More patients with Hb levels＞100 g/L in whom with lower differences in PNH clone size between erythrocyte and neutrophil(40％vs.100％,P=0.024).Twelve patients had elevated LDH levels.All 12 patients with elevated LDH showed＞10％lower type Ⅱ+Ⅲ erythrocyte clones compared to neutrophil clones.Hb＞100 g/L was achieved in 25％(3/12)of elevated LDH patients vs.77％(10/13)of normal LDH patients(25％vs.77％,P=0.013).3 patients experienced breakthrough hemolysis(BTH),all occurring after 32(15-91)days of delayed Eculizumab administration.Conclusion Persistent anemia post-Eculizumab treatment in high disease activity statePNHcorrelates significantly with concurrent aplastic anemia,extravascular hemolysis,residual intravascular hemolysis and breakthrough hemolysis.
Keywords：paroxysmal nocturnal hemoglobinuriahigh disease-activity statusEculizumabpersistent anemia etiology
Publication Date：2025-07-01
Online Publishing Date：2025-09-04(First online date of this platform, not the publication date of the document)
Pages：8( 593-599,605 )