Blood Res.  2017 Sep;52(3):207-211. 10.5045/br.2017.52.3.207.

Efficacy of eculizumab in paroxysmal nocturnal hemoglobinuria patients with or without aplastic anemia: prospective study of a Korean PNH cohort

• Choi CW
• Jang JH
• Kim JS
• Jo DY
• Lee JH
• Kim SH
• Kim YK
• Won JH
• Chung JS
• Kim H
• Lee JH
• Kim MK
• Eom HS
• Hyun SY
• Kim JA
• Lee JW

• KMID: 2390983
• DOI: http://doi.org/10.5045/br.2017.52.3.207

Abstract

BACKGROUND
Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab-treated patients show clinical benefit regardless of concurrent AA.
METHODS
We analyzed 46 PNH patients ≥18 years of age who were diagnosed by flow cytometry and treated with eculizumab for more than 6 months in the prospective Korean PNH registry. Patients were categorized into two groups: PNH patients with concurrent AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of intravascular hemolysis, hematological laboratory values, transfusion requirement, and PNH-associated complications were assessed at baseline and every 6 months after initiation of eculizumab treatment.
RESULTS
The median patient age was 46 years and median duration of eculizumab treatment was 34 months. Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month follow-up, LDH decreased to near normal levels in all patients; this effect was maintained until the 36-month follow-up regardless of concurrent AA. Transfusion independence was achieved by 53.3% of patients within the first 6 months of treatment and by 90.9% after 36 months of treatment. The mean number of RBC units transfused was significantly reduced, from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population; this effect was similar in both PNH/AA and classic PNH.
CONCLUSION
This study demonstrated that eculizumab is beneficial in the management of patients with PNH/AA, similar to classic PNH.

Keyword

Paroxysmal nocturnal hemoglobinuria; Aplastic anemia; Complement C5 inhibitor; Eculizumab

MeSH Terms

Anemia, Aplastic*
Cohort Studies*
Flow Cytometry
Follow-Up Studies
Hemoglobinuria, Paroxysmal*
Hemolysis
Humans
Prospective Studies*

Figure

• 

  Fig. 1 Reduction in hemolysis after eculizumab. Treatment with eculizumab induced rapid and consistent inhibition of hemolysis to near normal levels in all patients after 36 months of follow-up. Patients with both PNH/AA and classic PNH had significant median change of LDH level. P-values compared with baseline were assessed using Wilcoxon signed-rank test. Abbreviations: AA, aplastic anemia; ecu, eculizumab; PNH, paroxysmal nocturnal hemoglobinuria; ULN, upper limit of normal.

• 

  Fig. 2 Improvement of anemia after eculizumab. In both patients with PNH/AA and classic PNH, hemoglobin levels were significantly improved after the first 6 months of eculizumab treatment; the effect (hemoglobin above 10 g/dL) was sustained after 36 months. P-values compared with baseline were assessed by Wilcoxon signed-rank test. Abbreviations: AA, aplastic anemia; ecu, eculizumab; PNH, paroxysmal nocturnal hemoglobinuria.

• 

  Fig. 3 Reduction of transfusion requirement after eculizumab. The mean number of packed RBC units transfused was significantly reduced from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population. P-values compared with baseline were assessed by Wilcoxon signed-rank test. Abbreviations: AA, aplastic anemia; ecu, eculizumab; PNH, paroxysmal nocturnal hemoglobinuria; RBC, red blood cells.

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