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Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study

Bone Marrow Transplantation volume 56, pages 2600–2602 (2021)Cite this article

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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by complement-mediated intravascular hemolysis, bone marrow failure, and thrombophilia [1, 2]. Eculizumab (Ecu) targets complement component 5 (C5), controls intravascular hemolysis, and prevents thrombotic complications, accounting for significant improvement in survival and quality of life [3, 4]. Despite the remarkable improvement in survival, hematological benefits during Ecu treatment remain heterogeneous. A substantial proportion of patients either remain anemic or require transfusion support, negatively impacting event-free survival and quality of life [5, 6]. Persistent anemia during Ecu is multifactorial and is not only restricted to C3d mediated extravascular hemolysis (EVH). In the era of novel anti-complement therapies, especially proximal complement pathway inhibitors, we investigated the quality of hematological response to Ecu in PNH patients.

We recently proposed a classification of hematological response to anti-complement therapies based on hemoglobin, red blood cell transfusion (RBC), and markers of hemolysis (LDH) and absolute reticulocyte count (ARC) [7]. This classification aimed to identify the mechanisms behind the different hematological responses, which might help identify the potential benefits of novel complement inhibitors. Six distinct biological categories were determined using hemoglobin, LDH, and ARC during Ecu treatment (Supplementary Table I).

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Fig. 1: Response to Eculizumab for PNH patients.

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Acknowledgements

The authors would like to thank the patients with PNH and their families. The authors also would like to thank the nurses and physicians who cared for these patients and their families.

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Authors and Affiliations

  1. French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Saint-Louis hospital, Paris, France

    Pierre-Edouard Debureaux, Flore Sicre de Fontbrune, Pedro Henrique Prata, Regis Peffault de Latour & Camilla Frieri

  2. Department of Hematological Medicine, King’s College Hospital, National Institute of Health Research/Welcome King’s Clinical Research Facility and King’s College London, London, United Kingdom

    Austin G. Kulasekararaj, Vasundhara Mallikarjuna, Shreyans Gandhi & Joanna Large

  3. Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation, Leiden, the Netherlands

    Austin G. Kulasekararaj, Antonio M. Risitano & Regis Peffault de Latour

  4. Federico II University of Naples, Department of Clinical Medicine and Surgery, Naples, Italy

    Fabiana Cacace, Antonio M. Risitano & Camilla Frieri

  5. Department of Medical Imaging, Hematology, and Oncology, University of São Paulo, Ribeirão Preto, SP, Brazil

    Bruno G. P. Silva, Rodrigo T. Calado & Pedro Henrique Prata

  6. Laboratory of Cancer Genetics and Gene Transfer, Core Research Laboratory - Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Florence, Italy

    Federica Barone & Rosario Notaro

  7. Department of Hematology, University of Florence, Florence, Italy

    Federica Barone & Michela Sica

  8. University of Paris, Paris, France

    Pedro Henrique Prata & Regis Peffault de Latour

  9. Clinical investigation center, Saint-Louis Hospital, Paris, France

    Juliette Soret

  10. Division of Hematology, Hospital A Beneficência Portuguesa, Sao Paulo, Brazil

    Phillip Scheinberg

  11. AORN Moscati, Hematology and Transplant Unit, Avellino, Italy

    Antonio M. Risitano

Authors
  1. Pierre-Edouard Debureaux
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  2. Austin G. Kulasekararaj
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  15. Joanna Large
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  16. Antonio M. Risitano
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  17. Regis Peffault de Latour
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  18. Camilla Frieri
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On behalf of the Severe Aplastic Anemia Working Party of the European Group for Bone Marrow Transplantation

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Correspondence to Pierre-Edouard Debureaux.

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Competing interests

AGK has received Honoraria from Alexion, Celgene, Novartis, Amgen, Ra Pharma. FSF has received Honoraria and research funding from Alexion and Novartis. RN has received lecture fees from Alexion and has served as member of an advisory board for Biocryst. AMR has received research funding from Ra Pharma, Achillion, Novartis, Apellis, Alexion, Alnylam and received Honoraria from Pfizer, Appelis, and Alexion. RPL has received research funding from Pfizer, Alexion, Novartis and Amgen. Other authors declare no competing financial interests.

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Debureaux, PE., Kulasekararaj, A.G., Cacace, F. et al. Categorizing hematological response to eculizumab in paroxysmal nocturnal hemoglobinuria: a multicenter real-life study. Bone Marrow Transplant 56, 2600–2602 (2021). https://doi.org/10.1038/s41409-021-01372-0

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