Review
Medicine, General & Internal
Bruno Fattizzo, Fabio Serpenti, Juri Alessandro Giannotta, Wilma Barcellini
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is an intriguing disease with ongoing research on its pathophysiology, diagnostics, and treatment. Advanced flow cytometry techniques have enabled detection of small PNH clones, but data interpretation remains challenging. New complement inhibitors may improve patients' quality of life and response rates, but questions regarding their use and long-term safety need further investigation.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Immunology
Melissa A. Colden, Sushant Kumar, Bolormaa Munkhbileg, Daria V. Babushok
Summary: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a disease that involves mutations in a specific gene, leading to hemolysis and abnormal clonal expansion of blood cells. The mechanisms behind this expansion are still debated, but recent advancements in research and technology offer new opportunities for understanding the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Gloria F. Gerber, Robert A. Brodsky
Summary: This article discusses the theoretical basis and clinical studies of using C3 inhibitors in the treatment of PNH, as well as provides suggestions for treatment sequencing.
Article
Oncology
Eleni Gavriilaki, Athanasios Tragiannidis, Maria Papathanasiou, Sotiria Besikli, Paraskevi Karvouni, Vassiliki Douka, Eleni Paphianou, Emmanuel Hatzipantelis, Giorgos Papaioannou, Anastasia Athanasiadou, Anastasia Marvaki, Alkistis-Kira Panteliadou, Anna Vardi, Ioannis Batsis, Antonia Syrigou, Despina Mallouri, Chrysavgi Lalayanni, Ioanna Sakellari
Summary: This study aims to investigate the efficiency and safety of therapeutic methods for aplastic anemia and paroxysmal nocturnal hemoglobinuria. The study found that novel treatments are changing the field of BMF syndromes, but further research is needed to personalize algorithms.
FRONTIERS IN ONCOLOGY
(2022)
Review
Hematology
Austin G. Kulasekararaj, Ioanna Lazana
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by deficiency of GPI-linked complement regulators. Despite the introduction of C5 inhibitors, residual hemolysis still occurs, leading to anemia and transfusion dependency in some patients. The development of longer-acting and subcutaneous formulations of C5 inhibitors, as well as proximal complement inhibitors, have shown promising results in improving hemoglobin levels and reducing hemolysis. Combination treatments have also been explored. This review discusses the current therapeutic options and emerging approaches for PNH.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Hematology
Jens Panse
Summary: In the past 20 years, therapy for paroxysmal nocturnal hemoglobinuria (PNH) mainly relied on antibody-based terminal complement inhibition. PNH is a disease characterized by a mutation that causes the absence or deficiency of complement-regulatory proteins on blood cells, leading to intravascular hemolysis and related complications. Recently, there has been a development of new drugs targeting the proximal and terminal complement cascade, with the approval of the first proximal complement inhibitor targeting C3 in 2021. This article aims to provide an overview of the progress made in PNH treatment and discuss the approved therapeutic options, as well as the potential impact and consequences of current and future treatments on patients' lives.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Bruno G. P. Pires da Silva, Natasha P. Fonseca, Luis Fernando B. Catto, Gabriel C. Pereira, Rodrigo T. Calado
Summary: This study retrospectively analyzed 87 cases of PNH in a Brazilian referral center and found that PNH presentation was variable, with most patients having subclinical disease or associated with bone marrow failure. The clone size remained stable or even disappeared in most cases.
ANNALS OF HEMATOLOGY
(2022)
Article
Hematology
Raymond Siu Ming Wong, Juan Ramon Navarro-Cabrera, Narcisa Sonia Comia, Yeow Tee Goh, Henry Idrobo, Daolada Kongkabpan, David Gomez-Almaguer, Mohammed Al-Adhami, Temitayo Ajayi, Paulo Alvarenga, Jessica Savage, Pascal Deschatelets, Cedric Francois, Federico Grossi, Teresita Dumagay
Summary: PNH is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan, the first C3-targeted therapy, has shown superior efficacy and safety compared to supportive care in complement inhibitor-naive patients with PNH, leading to significant stabilization of hemoglobin levels and reduction in lactate dehydrogenase levels.
Article
Pharmacology & Pharmacy
Jun-ichi Nishimura, Antoine Soubret, Noriko Arase, Simon Buatois, Masaki Hotta, Jean-Eric Charoin, Yoshikazu Ito, Sasha Sreckovic, Hiroyuki Takamori, Christoph Bucher, Yasutaka Ueda, Jules Hernandez-Sanchez, Keisuke Gotanda, Gregor Jordan, Kenji Shinomiya, Julia Ramos, Jin Seok Kim, Jens Panse, Regis Peffault de Latour, Alexander Roeth, Eiichi Morii, Hubert Schrezenmeier, Yoshitaka Isaka, Simona Sica, Yuzuru Kanakura, Sung-Soo Yoon, Taroh Kinoshita, Ido Paz-Priel, Alexandre Sostelly
Summary: Drug-target-drug complexes (DTDCs) are newly observed phenomena in patients switching from eculizumab to crovalimab. Optimizing crovalimab dosing reduces the proportion of large DTDCs, ensures adequate complement inhibition, and may improve safety.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Patricia Eiko Yamakawa, Ana Rita Fonseca, Ismael Dale Cotrim Guerreiro da Silva, Matheus Vescovi Goncalves, Dirce Maria Marchioni, Antonio Augusto Ferreira Carioca, David Michonneau, Celso Arrais-Rodrigues
Summary: This study aimed to identify the dysfunctional pathways involved in the pathophysiology of PNH by comparing the metabolic profiles of PNH patients to healthy controls, as well as analyzing the metabolomic profiles before and after eculizumab treatment. The results showed significant differences in metabolomes between PNH patients and healthy controls, and eculizumab treatment appeared to improve defects in the Acyl CoA metabolism, reducing oxidative stress and inflammation.
Article
Hematology
Kohei Hosokawa, Shinji Nakao
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder caused by a PIGA gene mutation. Clonal expansion of GPI(-) cells is common in PNH, but tiny GPI(-) cell populations can also be found in healthy individuals. In patients with acquired aplastic anemia, the expansion of PNH clones is related to immune attack on hematopoietic stem cells. However, the mechanisms underlying the selection and expansion of GPI(-) cells remain unclear.
SEMINARS IN HEMATOLOGY
(2022)
Review
Oncology
Juri Alessandro Giannotta, Bruno Fattizzo, Wilma Barcellini
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is associated with aplastic anemia and myelodysplastic syndromes, with a prevalence of PNH clones in MPN patients around 10%, commonly associated with JAK2V617F-positive myelofibrosis. Thrombotic events are a common clinical presentation in this combination, sometimes refractory to treatment, and the use of eculizumab may only provide partial effectiveness in controlling hemolytic anemia, necessitating careful evaluation of risk/benefit in this peculiar setting.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Sung-Eun Lee, Jong Wook Lee
Summary: This article reviews the safety data of eculizumab and ravulizumab in the treatment of PNH, especially in special settings. Expert opinion suggests that both drugs have been found to be safe and well tolerated in clinical trials, but vigilance towards meningococcal infections is still necessary.
EXPERT OPINION ON DRUG SAFETY
(2021)
Article
Medicine, General & Internal
Peter Hillmen, Jeff Szer, Ilene Weitz, Alexander Roeth, Britta Hoechsmann, Jens Panse, Kensuke Usuki, Morag Griffin, Jean-Jacques Kiladjian, Carlos de Castro, Hisakazu Nishimori, Lisa Tan, Mohamed Hamdani, Pascal Deschatelets, Cedric Francois, Federico Grossi, Temitayo Ajayi, Antonio Risitano, Regis Peffault de la Tour
Summary: The study demonstrated that Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Hematology
Deniz Goren Sahin, Olga Meltem Akay, Muzaffer Keklik, Vahap Okan, Abdullah Karakus, Cengiz Demir, Mehmet Ali Erkurt, Kadir Ilkkilic, Rahsan Yildirim, Gulsum Akgun Cagliyan, Salih Aksu, Mehmet Hilmi Dogu, Mehmet Sinan Dal, Volkan Karakus, Ali Ihsan Gemici, Hatice Terzi, Engin Kelkitli, Serdar Sivgin, Ali Unal, Mehmet Yilmaz, Orhan Ayyildiz, Serdal Korkmaz, Bulent Eser, Fevzi Altuntas
Summary: This study aimed to collect PNH patient data from hematology centers across Turkey to identify clinical features and management. After evaluating patients from 19 different institutions, it was found that fatigue and abdominal pain were the most frequent presenting symptoms. This study provided valuable information for understanding the disease and differences between patients in Turkey and existing literature.
ANNALS OF HEMATOLOGY
(2021)