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A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal hematopoietic stem cell disorder, is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state. The EXPLORE study aimed to determine the prevalence of un...

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Autores principales: Raza, Azra, Ravandi, Farhad, Rastogi, Anjay, Bubis, Jeffrey, Lim, Seah H., Weitz, Ilene, Castro-Malaspina, Hugo, Galili, Naomi, Jawde, Rony Abou, Illingworth, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594745/
https://www.ncbi.nlm.nih.gov/pubmed/24227693
http://dx.doi.org/10.1002/cyto.b.21139
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author Raza, Azra
Ravandi, Farhad
Rastogi, Anjay
Bubis, Jeffrey
Lim, Seah H.
Weitz, Ilene
Castro-Malaspina, Hugo
Galili, Naomi
Jawde, Rony Abou
Illingworth, Andrea
author_facet Raza, Azra
Ravandi, Farhad
Rastogi, Anjay
Bubis, Jeffrey
Lim, Seah H.
Weitz, Ilene
Castro-Malaspina, Hugo
Galili, Naomi
Jawde, Rony Abou
Illingworth, Andrea
author_sort Raza, Azra
collection PubMed
description BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal hematopoietic stem cell disorder, is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state. The EXPLORE study aimed to determine the prevalence of undiagnosed PNH in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), and/or other bone marrow failure (BMF) syndromes and the effect of PNH clone size on hemolysis. METHODS: Patients, selected from medical office chart reviews, had blood samples collected for hematologic panel testing and for flow cytometry detection of PNH clones. RESULTS: Granulocyte PNH clones ≥ 1% were detected in 199 of all 5,398 patients (3.7%), 93 of 503 AA patients (18.5%), 50 of 4,401 MDS patients (1.1%), and 3 of 130 other BMF patients (2.3%). Higher-sensitivity analyses detected PNH clones ≥ 0.01% in 167 of 1,746 patients from all groups (9.6%) and in 22 of 1,225 MDS patients (1.8%), 116 of 294 AA patients (39.5%), and four of 54 other BMF patients (7.8%). Among patients with PNH clones ≥ 1%, median clone size was smaller in patients with AA (5.1%) than in those with MDS (17.6%) or other BMF (24.4%), and the percentage of patients with lactate dehydrogenase levels (a marker for intravascular hemolysis) ≥ 1.5 × upper limit of normal was smaller in patients with AA (18.3%) than in those with MDS (42.0%). CONCLUSIONS: These results confirm the presence of PNH clones in high-risk patient groups and suggest that screening of such patients may facilitate patient management and care.
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spelling pubmed-55947452017-09-12 A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure Raza, Azra Ravandi, Farhad Rastogi, Anjay Bubis, Jeffrey Lim, Seah H. Weitz, Ilene Castro-Malaspina, Hugo Galili, Naomi Jawde, Rony Abou Illingworth, Andrea Cytometry B Clin Cytom Article BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal hematopoietic stem cell disorder, is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state. The EXPLORE study aimed to determine the prevalence of undiagnosed PNH in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), and/or other bone marrow failure (BMF) syndromes and the effect of PNH clone size on hemolysis. METHODS: Patients, selected from medical office chart reviews, had blood samples collected for hematologic panel testing and for flow cytometry detection of PNH clones. RESULTS: Granulocyte PNH clones ≥ 1% were detected in 199 of all 5,398 patients (3.7%), 93 of 503 AA patients (18.5%), 50 of 4,401 MDS patients (1.1%), and 3 of 130 other BMF patients (2.3%). Higher-sensitivity analyses detected PNH clones ≥ 0.01% in 167 of 1,746 patients from all groups (9.6%) and in 22 of 1,225 MDS patients (1.8%), 116 of 294 AA patients (39.5%), and four of 54 other BMF patients (7.8%). Among patients with PNH clones ≥ 1%, median clone size was smaller in patients with AA (5.1%) than in those with MDS (17.6%) or other BMF (24.4%), and the percentage of patients with lactate dehydrogenase levels (a marker for intravascular hemolysis) ≥ 1.5 × upper limit of normal was smaller in patients with AA (18.3%) than in those with MDS (42.0%). CONCLUSIONS: These results confirm the presence of PNH clones in high-risk patient groups and suggest that screening of such patients may facilitate patient management and care. 2013-11-12 2014-05 /pmc/articles/PMC5594745/ /pubmed/24227693 http://dx.doi.org/10.1002/cyto.b.21139 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution NonCommercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is noncommercial and no modifications or adaptations are made.
spellingShingle Article
Raza, Azra
Ravandi, Farhad
Rastogi, Anjay
Bubis, Jeffrey
Lim, Seah H.
Weitz, Ilene
Castro-Malaspina, Hugo
Galili, Naomi
Jawde, Rony Abou
Illingworth, Andrea
A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure
title A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure
title_full A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure
title_fullStr A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure
title_full_unstemmed A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure
title_short A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure
title_sort prospective multicenter study of paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594745/
https://www.ncbi.nlm.nih.gov/pubmed/24227693
http://dx.doi.org/10.1002/cyto.b.21139
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