Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria
BackgroundParoxysmal nocturnal hemoglobinuria (PNH) is a rare complement-driven acquired hemolytic anemia with specific presentations of hemoglobinuria, abdominal pain, fatigue, and thrombosis.ObjectiveTo review the current therapeutic strategies for PNH, including anti-complement therapy and alloge...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1521484/full |
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| author | Marek Ussowicz Dawid Przystupski Patrycja Mensah-Glanowska Agnieszka Piekarska |
| author_facet | Marek Ussowicz Dawid Przystupski Patrycja Mensah-Glanowska Agnieszka Piekarska |
| author_sort | Marek Ussowicz |
| collection | DOAJ |
| description | BackgroundParoxysmal nocturnal hemoglobinuria (PNH) is a rare complement-driven acquired hemolytic anemia with specific presentations of hemoglobinuria, abdominal pain, fatigue, and thrombosis.ObjectiveTo review the current therapeutic strategies for PNH, including anti-complement therapy and allogeneic hematopoietic cell transplantation (alloHCT), focusing on the tailoring of the approach to the disease subtype.ResultsThe outcome of alloHCT varies depending on disease severity, thrombotic history, and response to prior therapies. Non-transplant PNH therapies include anti-C5 monoclonal antibodies that reduce terminal complement activation (eculizumab, ravulizumab, and crovalimab) and proximal complement pathway inhibitors such as pegcetacoplan (C3 inhibitor), iptacopan (complement factor B inhibitor), and danicopan (complement factor D inhibitor). Although complement inhibitors have revolutionized treatment, alloHCT remains the only curative therapy, particularly for patients who are refractory to medical management or have severe cytopenia. This review outlines the conditioning regimens used in alloHCT and summarizes recent studies showing that overall survival rates improve with less toxic conditioning protocols.ConclusionsAlloHCT can be used to manage PNH, particularly in patients who are resistant to or without access to complement-targeted therapies. Any potential cure offered by alloHCT must be counterbalanced by the significant procedure risks, including graft-versus-host disease and transplant-related mortality, particularly in patients with comorbidities. In the case of severe aplastic anemia with an associated PNH clone, immunoablative protocols based on anti-thymocyte globulin serotherapy with fludarabine and cyclophosphamide are recommended. The use of reduced toxicity protocols with fludarabine has been well-documented in patients with classic PNH. A treosulfan/fludarabine-based regimen is recommended; however, there is no consensus on optimal drug selection. |
| format | Article |
| id | doaj-art-92f6aa96f5ca477bb38bb9f171e23f96 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-92f6aa96f5ca477bb38bb9f171e23f962025-01-07T06:41:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15214841521484Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuriaMarek Ussowicz0Dawid Przystupski1Patrycja Mensah-Glanowska2Agnieszka Piekarska3Department of Paediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University; Supraregional Centre of Paediatric Oncology “Cape of Hope”, Wrocław, PolandDepartment of Paediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University; Supraregional Centre of Paediatric Oncology “Cape of Hope”, Wrocław, PolandDepartment of Hematology, Jagiellonian University Collegium Medicum, University Hospital in Cracow, Kraków, PolandDepartment of Hematology and Transplantology, Medical University of Gdansk, Gdansk, PolandBackgroundParoxysmal nocturnal hemoglobinuria (PNH) is a rare complement-driven acquired hemolytic anemia with specific presentations of hemoglobinuria, abdominal pain, fatigue, and thrombosis.ObjectiveTo review the current therapeutic strategies for PNH, including anti-complement therapy and allogeneic hematopoietic cell transplantation (alloHCT), focusing on the tailoring of the approach to the disease subtype.ResultsThe outcome of alloHCT varies depending on disease severity, thrombotic history, and response to prior therapies. Non-transplant PNH therapies include anti-C5 monoclonal antibodies that reduce terminal complement activation (eculizumab, ravulizumab, and crovalimab) and proximal complement pathway inhibitors such as pegcetacoplan (C3 inhibitor), iptacopan (complement factor B inhibitor), and danicopan (complement factor D inhibitor). Although complement inhibitors have revolutionized treatment, alloHCT remains the only curative therapy, particularly for patients who are refractory to medical management or have severe cytopenia. This review outlines the conditioning regimens used in alloHCT and summarizes recent studies showing that overall survival rates improve with less toxic conditioning protocols.ConclusionsAlloHCT can be used to manage PNH, particularly in patients who are resistant to or without access to complement-targeted therapies. Any potential cure offered by alloHCT must be counterbalanced by the significant procedure risks, including graft-versus-host disease and transplant-related mortality, particularly in patients with comorbidities. In the case of severe aplastic anemia with an associated PNH clone, immunoablative protocols based on anti-thymocyte globulin serotherapy with fludarabine and cyclophosphamide are recommended. The use of reduced toxicity protocols with fludarabine has been well-documented in patients with classic PNH. A treosulfan/fludarabine-based regimen is recommended; however, there is no consensus on optimal drug selection.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1521484/fullPNHaplastic anemiahematopoietic cell transplantationparoxysmal nocturnal hemoglobinuriaconditioning |
| spellingShingle | Marek Ussowicz Dawid Przystupski Patrycja Mensah-Glanowska Agnieszka Piekarska Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria Frontiers in Immunology PNH aplastic anemia hematopoietic cell transplantation paroxysmal nocturnal hemoglobinuria conditioning |
| title | Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria |
| title_full | Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria |
| title_fullStr | Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria |
| title_full_unstemmed | Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria |
| title_short | Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria |
| title_sort | current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria |
| topic | PNH aplastic anemia hematopoietic cell transplantation paroxysmal nocturnal hemoglobinuria conditioning |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1521484/full |
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