Features, reason for testing, and changes with time of 583 paroxysmal nocturnal hemoglobinuria clones from 529 patients: a multicenter Italian study

Cannizzo, Elisa; Raia, Maddalena; Propris, Maria Stefania De; Triolo, Anna; Scarpati, Barbara; Marfia, Anna; Stacchini, Alessandra; Buccisano, Francesco; Lanza, Francesco; Regazzoli, Antonio; Michelutti, Angela; Cesaro, Simone; Conte, Cinzia Armentano; Vanelli, Laura; Tedone, Elisabetta; Omedè, Paola; Ciriello, Maria Matilde; Caporale, Roberto; Catinella, Virginia; Pantano, Giorgia; Rosa, Clorinda De; Pardo, Catia Lo; Poletti, Giovanni; Ulbar, Francesca; Pavanelli, Maria Cristina; Pup, Laura Del; Ottaviano, Virginia; Santonocito, Anna Maria; Bartocci, C; Boscaro, Elisa; Arras, Marcella; Amodeo, Rachele; Mestice, Anna; Oliva, Bianca; Ferrari, Luisa; Statuto, Teodora; D’Auria, Fiorella; Pianezze, Graziano; Tanca, Donatella; Visconte, Feliciano; Rubba, F.; Musto, Pellegrino; Geuna, Massimo; Gatti, Arianna; Brando, Bruno; Vecchio, Luigi Del

doi:10.1007/s00277-019-03644-8

Cited by 9 publications

(16 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PIGA muta tions occur early in hema to poi e sis in hema to poietic stem cells or multipotent pro gen i tors. 7,12,14,15 In most patients, PNH clones can be detected in all or most mature hema to poietic lin e ages, includ ing granulocytes, mono cytes, plate lets, RBCs, and the B, T, and nat u ral killer cells. 7,12,15 More lim ited lin eage involve ment can occur but is more char ac ter is tic of MDS, in which PNH clones are also more likely to be tran sient.…”

Section: Clinical Case 1: False-positive Pnh Testmentioning

confidence: 99%

“…In such cases, prior subclin i cal mar row fail ure is fre quently pre sumed; alter na tively, sec ond ary pro lif er a tive muta tions within a PNH HSPC can pro mote PNH clone expan sion. 1,13 Studies of patients with pos i tive PNH fl ow cytom e try results have found that PNH clones have a bimodal size dis tri bu tion closely related to the patients ' clin i cal presen ta tions 12,14 ( Figure 1 , Table 1 ). Approximately one -third of patients have "clas si cal PNH," with overt hemo ly sis, mul ti ple PNH symp toms, and an increased risk of throm bo ses.…”

Section: Introductionmentioning

confidence: 99%

“…1 PNH clones can also emerge in patients with myelodysplastic syn drome (MDS) and, more rarely, in patients with mye lo pro lif er a tive neo plasms. 11,12 Although immunemedi ated bone mar row fail ure is the pri mary risk fac tor for devel op ing PNH clones, patients can be diag nosed with clas si cal PNH with out a known diag no sis of bone mar row fail ure or a his tory of cytopenias. In such cases, prior subclin i cal mar row fail ure is fre quently pre sumed; alter na tively, sec ond ary pro lif er a tive muta tions within a PNH HSPC can pro mote PNH clone expan sion.…”

Section: Introductionmentioning

confidence: 99%

“…Patients with clas si cal PNH have a mean PNH clone size of more than 70%. 11,12 In con trast, two-thirds of PNH clones occur in patients who have cytopenias and bone mar row fail ure with out clin i cal hemo ly sis. Most bone mar row fail ure patients are largely asymptom atic from PNH and have small PNH clones (mean clone size of approx i ma tely 11%) (Figure 1, Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…Most bone mar row fail ure patients are largely asymptom atic from PNH and have small PNH clones (mean clone size of approx i ma tely 11%) (Figure 1, Table 1). 11,12 Interpreting the sig nif cance of a PNH flow cytom e try result…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

When does a PNH clone have clinical significance?

Babushok

2021

Hematology

View full text Add to dashboard Cite

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired blood disease caused by somatic mutations in the phosphatidylinositol glycan class A (PIGA) gene required to produce glycophosphatidyl inositol (GPI) anchors. Although PNH cells are readily identified by flow cytometry due to their deficiency of GPI-anchored proteins, the assessment of the clinical significance of a PNH clone is more nuanced. The interpretation of results requires an understanding of PNH pathogenesis and its relationship to immune-mediated bone marrow failure. Only about one-third of patients with PNH clones have classical PNH disease with overt hemolysis, its associated symptoms, and the highly prothrombotic state characteristic of PNH. Patients with classical PNH benefit the most from complement inhibitors. In contrast, two-thirds of PNH clones occur in patients whose clinical presentation is that of bone marrow failure with few, if any, PNH-related symptoms. The clinical presentations are closely associated with PNH clone size. Although exceptions occur, bone marrow failure patients usually have smaller, subclinical PNH clones. This review addresses the common scenarios that arise in evaluating the clinical significance of PNH clones and provides practical guidelines for approaching a patient with a positive PNH result.

show abstract

Section: Clinical Case 1: False-positive Pnh Testmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

When does a PNH clone have clinical significance?

Babushok

2021

Hematology

View full text Add to dashboard Cite

show abstract

Paroxysmal nocturnal hemoglobinuria: Where we stand

Panse

2023

American J Hematol

View full text Add to dashboard Cite

For the last 20 years, therapy of paroxysmal nocturnal hemoglobinuria (PNH) relied-up until recently-on antibody based terminal complement inhibitionon. PNH pathophysiology-a mutational defect leading to partial or complete absence of complement-regulatory proteins on blood cells-leads to intravascular hemolysis and consequences such as thrombosis and other sequelae. A plethora of new drugs interfering with the proximal and terminal complement cascade are under recent development and the first "proof-of-pinciple" proximal complement inhibitor targeting C3 has been approved in 2021. "PNH: where we stand" will try to give a brief account on where we came from and where we stand focusing on approved therapeutic options. The associated improvements as well as potential consequences of actual and future treatments as well as their impact on the disease will continue to necessitate academic and scientific focus on improving treatment options as well as on side effects and outcomes relevant to individual patient lives and circumstances in order to develop effective, safe, and available treatment for all hemolytic PNH patients globally.Note: Due to space limitation the author mostly cites reviews and overviews, giving readers the chance to easily find continuative summaries of potentially interesting topics. He therefore does apologize

show abstract

Immunophenotypic assessment ofPNHclones in major and minor cell lineages in the peripheral blood of patients with paroxysmal nocturnal hemoglobinuria

Richards

Dickinson

Newton

et al. 2022

Cytometry Part B Clinical

View full text Add to dashboard Cite

Background: Flow cytometric immunophenotyping is essential for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). Most cases have easy to interpret flow cytometry profiles with red cells, neutrophils and monocytes showing complete deficiency of glycophosphatidylinositol (GPI) linked antigen expression. Some cases are more challenging to interpret due to the presence of multiple populations of PNH cells and variable levels of GPI antigen expression.Methods: We studied 46 known PNH patients, many with complex immunophenotypic profiles using a novel, single tube, multi-parameter 7-color immunophenotyping assay that allowed simultaneous detection and assessment of PNH clones within multiple lineages of peripheral blood leucocytes. Red cell PNH clones were also assessed in total and immature (CD71+) components by CD59 expression. Results: For individual patients, total PNH clones in each cell lineage were highly correlated. Monocytes, eosinophils and basophils showed the highest proportions of PNH cells. Red cell PNH clones were typically smaller than monocyte and neutrophil PNH clones. In most cases, PNH clones were detectable in minor leucocyte populations where multiple populations of PNH cells were present, variability in the proportions of type II and type III cells was seen across different cell lineages, even though total PNH clones remained similar.Conclusions: This study shows that PNH patients with multiple PNH clones do not always display the same abnormality across all cell lineages routinely tested. There is no simple explanation for this but is likely due to a combination of complex molecular, genetic and biochemical dysfunction in different blood cell types.

show abstract

Features, reason for testing, and changes with time of 583 paroxysmal nocturnal hemoglobinuria clones from 529 patients: a multicenter Italian study

Cited by 9 publications

References 33 publications

When does a PNH clone have clinical significance?

When does a PNH clone have clinical significance?

Paroxysmal nocturnal hemoglobinuria: Where we stand

Immunophenotypic assessment ofPNHclones in major and minor cell lineages in the peripheral blood of patients with paroxysmal nocturnal hemoglobinuria

Contact Info

Product

Resources

About