Clinical and prognostic significance of small paroxysmal nocturnal hemoglobinuria clones in myelodysplastic syndrome and aplastic anemia.
Bruno Fattizzo,Bruno Fattizzo,Bruno Fattizzo,Robin M. Ireland,Alan Dunlop,Deborah Yallop,Shireen Kassam,Joanna Large,Shreyans Gandhi,Petra Muus,Charles Manogaran,Katy Sanchez,Dario Consonni,Wilma Barcellini,Ghulam J. Mufti,Ghulam J. Mufti,Judith C. W. Marsh,Judith C. W. Marsh,Austin G. Kulasekararaj,Austin G. Kulasekararaj +19 more
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TLDR
A large single-centre study as discussed by the authors reported high prevalence of paroxysmal nocturnal hemoglobinuria (PNH) clones by high-sensitive cytometry among 3085 patients tested.Abstract:
In this large single-centre study, we report high prevalence (25%) of, small (<10%) and very small (<1%), paroxysmal nocturnal hemoglobinuria (PNH) clones by high-sensitive cytometry among 3085 patients tested. Given PNH association with bone marrow failures, we analyzed 869 myelodysplastic syndromes (MDS) and 531 aplastic anemia (AA) within the cohort. PNH clones were more frequent and larger in AA vs. MDS (p = 0.04). PNH clone, irrespective of size, was a good predictor of response to immunosuppressive therapy (IST) and to stem cell transplant (HSCT) (in MDS: 84% if PNH+ vs. 44.7% if PNH−, p = 0.01 for IST, and 71% if PNH+ vs. 56.6% if PNH− for HSCT; in AA: 78 vs. 50% for IST, p < 0.0001, and 97 vs. 77%, p = 0.01 for HSCT). PNH positivity had a favorable impact on disease progression (0.6% vs. 4.9% IPSS-progression in MDS, p < 0.005; and 2.1 vs. 6.9% progression to MDS in AA, p = 0.01), leukemic evolution (6.8 vs. 12.7%, p = 0.01 in MDS), and overall survival [73% (95% CI 68–77) vs. 51% (48–54), p < 0.0001], with a relative HR for mortality of 2.37 (95% CI 1.8–3.1; p < 0.0001) in PNH negative cases, both in univariate and multivariable analysis. Our data suggest systematic PNH testing in AA/MDS, as it might allow better prediction/prognostication and consequent clinical/laboratory follow-up timing.read more
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The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
Joseph D. Khoury,Eric Solary,Oussama Abla,Yassmine Akkari,Rita Alaggio,Jane F. Apperley,Rafael Bejar,Emilio Berti,Lambert Busque,John K.C. Chan,Weina Chen,Xi Chen,Wee Joo Chng,John K. Choi,Isabel Colmenero,Sarah E. Coupland,Nicholas C.P. Cross,Daphne de Jong,M. Tarek Elghetany,Emiko Takahashi,Jean-François Emile,Judith A. Ferry,Linda Fogelstrand,Michaela Fontenay,Ulrich Germing,Sumeet Gujral,Torsten Haferlach,Claire N. Harrison,Jennelle C. Hodge,Shimin Hu,Joop H. Jansen,Rashmi Kanagal-Shamanna,Hagop M. Kantarjian,Christian P. Kratz,Xiao-Qiu Li,Megan S. Lim,Keith R. Loeb,Sanam Loghavi,Andrea N. Marcogliese,Soheil Meshinchi,Phillip Michaels,Kikkeri N. Naresh,Yasodha Natkunam,Reza Nejati,German Ott,Eric Padron,Keyur Patel,Nikhil Patkar,Jennifer Picarsic,Uwe Platzbecker,Irene Roberts,Anna Schuh,William C. Sewell,Reiner Siebert,Prashant Tembhare,Jeffrey W. Tyner,Srdan Verstovsek,Wei Wang,Brent L. Wood,W Q Xiao,Cecilia Yeung,Andreas Hochhaus +61 more
TL;DR: The 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database as discussed by the authors .
Journal ArticleDOI
Large Granular Lymphocyte Expansion in Myeloid Diseases and Bone Marrow Failure Syndromes: Whoever Seeks Finds
Bruno Fattizzo,Bruno Fattizzo,Valentina Bellani,Raffaella Pasquale,Juri Alessandro Giannotta,Wilma Barcellini +5 more
TL;DR: In this paper, the authors reviewed available literature regarding the association of large granular lymphocyte clones with myeloid neoplasms and bone marrow failures focusing on evidence of pathogenic, clinical, and prognostic relevance.
Journal ArticleDOI
The predictive value of PNH clones, 6p CN-LOH, and clonal TCR gene rearrangement for aplastic anemia diagnosis.
Yash B. Shah,Salvatore F. Priore,Yimei Li,Chi N. Tang,Peter Nicholas,Peter Kurre,Timothy S. Olson,Daria V. Babushok,Daria V. Babushok +8 more
TL;DR: In this paper, the authors proposed to distinguish acquired aplastic anemia (AA) from inherited bone marrow failure syndromes using three laboratory findings specific to the autoimmune pathogenesis of AA: paroxysmal nocturnal hemoglobinuria (PNH) clones, copy-number-neutral loss of heterozygosity in chromosome arm 6p (6p CN-LOH), and clonal T-cell receptor (TCR) γ gene rearrangement.
Journal ArticleDOI
Low-Risk Myelodysplastic Syndrome Revisited: Morphological, Autoimmune, and Molecular Features as Predictors of Outcome in a Single Center Experience
Bruno Fattizzo,Giorgia Levati,Juri Alessandro Giannotta,Giulio Cassanello,Lilla Cro,Anna Zaninoni,Marzia Barbieri,Giorgio Alberto Croci,Nicoletta Revelli,Wilma Barcellini +9 more
TL;DR: G granular evaluation and re-evaluation are pivotal in LR-MDS patients to optimize clinical management and to optimized clinical management of molecular lesions and autoimmune phenomena.
References
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Journal ArticleDOI
Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry.
Michael J. Borowitz,Fiona E. Craig,Joseph A. DiGiuseppe,Andrea Illingworth,Wendell F. Rosse,D. Robert Sutherland,Carl T. Wittwer,Stephen J. Richards +7 more
TL;DR: Flow cytometry is the method of choice for identifying cells deficient in GPI‐linked proteins and is, therefore, necessary for the diagnosis of PNH, but to date there has not been an attempt to standardize the methodology used to identify these cells.
Journal ArticleDOI
Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia.
Chiharu Sugimori,Tatsuya Chuhjo,Xingmin Feng,Hirohito Yamazaki,Akiyoshi Takami,Masanao Teramura,Hideaki Mizoguchi,Mitsuhiro Omine,Shinji Nakao +8 more
TL;DR: Results indicate that a minor population of PNH-type cells represents a reliable marker of a positive IST response and a favorable prognosis among patients with AA, and immune attack against hematopoietic stem cells that allows PNH clonal expansion might occur only at the onset of AA.
Journal ArticleDOI
Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome
Hongbo Wang,Tatsuya Chuhjo,Tatsuya Chuhjo,Shizuka Yasue,Shizuka Yasue,Mitsuhiro Omine,Mitsuhiro Omine,Shinji Nakao,Shinji Nakao +8 more
TL;DR: The presence of a minor population of P NH-type cells suggests a benign type of bone marrow failure, probably caused by an immunologic mechanism, and peripheral blood should be tested using sensitive flow cytometry for the presence of PNH- type cells in all patients withBone marrow failure before treatment.
Journal ArticleDOI
Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia
TL;DR: In the era of IST, the baseline ARC and ALC together serve as a simple predictor of response following IST, which should guide in risk stratification among patients with SAA.
Journal ArticleDOI
The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort
Maximilian Stahl,Michelle DeVeaux,Theo de Witte,Judith Neukirchen,Mikkael A. Sekeres,Andrew M. Brunner,Gail J. Roboz,David P. Steensma,Vijaya Raj Bhatt,Uwe Platzbecker,Thomas Cluzeau,Pedro Henrique Prata,Raphael Itzykson,Pierre Fenaux,Amir T. Fathi,Alexandra Smith,Ulrich Germing,Ellen K. Ritchie,Vivek Verma,Aziz Nazha,Jaroslaw P. Maciejewski,Nikolai A. Podoltsev,Thomas Prebet,Valeria Santini,Steven D. Gore,Rami S. Komrokji,Amer M. Zeidan +26 more
TL;DR: IT leads to objective responses in nearly half the selected patients with the highest rate of RBC TI achieved in patients with hypocellular bone marrows, and age, transfusion dependence, presence of paroxysmal nocturnal hemoglobinuria or large granular lymphocyte clones, and HLA DR15 positivity did not predict response to IST.
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