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Serologic response to meningococcal vaccination in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with the terminal complement inhibitor eculizumab

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Abstract

Eculizumab is indicated for the therapy of patients with symptomatic paroxysmal nocturnal hemoglobinuria (PNH). Due to inhibition of terminal complement cascade, patients on eculizumab are susceptible to Neisseria meningitidis infections. The two mainstays to reduce the risk of infection are vaccination and antibiotic prophylaxis. In this retrospective study, serologic response was analyzed after vaccination with a meningococcal vaccine in 23 PNH patients (median age 36 years; range 25 - 88 years; 15 males, 8 females) by measuring serum bactericidal assay (SBA) using rabbit complement (rSBA) titers against meningococcal serogroups A, C, W, and Y. Serologic protection was defined by an rSBA titer ≥1:8. Forty-three percent (10/23) were vaccinated more than once due to chronic eculizumab treatment. Overall serologic response for the meningococcal serogroups was A: 78% (18/23), C: 87% (20/23), W: 48% (11/23), and Y: 70% (16/23). No meningococcal infections have been observed. As immunological response to vaccines varies, the use of serologic response analyses is warranted. Re-vaccination with a tetravalent conjugate vaccine under eculizumab therapy every 3 years is essential or should be based on response rates. If meningococcal infection is suspected, standby therapy with ciprofloxacin and immediate medical evaluation are recommended. The novel vaccines covering serogroup B may even further reduce the risk for infection.

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Abbreviations

PNH:

Paroxysmal nocturnal hemoglobinuria

rSBA:

Serum bactericidal assay (SBA) using rabbit complement (rSBA)

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Authors and Affiliations

  1. Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany

    Ferras Alashkar, Dörte Herich-Terhürne, Nicole Preising, Ulrich Dührsen & Alexander Röth

  2. Rheinisch-Westfälisches Institut für Wirtschaftsforschung, Essen, Germany

    Colin Vance

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  1. Ferras Alashkar
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  2. Colin Vance
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  3. Dörte Herich-Terhürne
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  4. Nicole Preising
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  5. Ulrich Dührsen
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  6. Alexander Röth
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Correspondence to Alexander Röth.

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Alashkar, F., Vance, C., Herich-Terhürne, D. et al. Serologic response to meningococcal vaccination in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with the terminal complement inhibitor eculizumab. Ann Hematol 96, 589–596 (2017). https://doi.org/10.1007/s00277-017-2924-y

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  • DOI: https://doi.org/10.1007/s00277-017-2924-y

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