Journal ArticleDOI
VPS 45-associated primary infantile myelofibrosis--successful treatment with hematopoietic stem cell transplantation.
Polina Stepensky,Natalia Simanovsky,Diana Averbuch,Menachem Gross,Asaf Yanir,Dror Mevorach,Orly Elpeleg,Michael Weintraub +7 more
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TLDR
The diagnosis of VPS 45‐associated PMF should be considered in all children presenting with SCN with subsequent development of pancytopenia, and long‐term follow‐up of these patients is necessary to identify extra‐hematological manifestations of V PS45 deficiency.Abstract:
PMF of infancy is a recently described autosomal recessive disorder presenting with severe bone marrow failure, accelerated neutrophil apoptosis, and significant platelet dysfunction, caused by a mutation in the VPS45 gene. In this study, we update our group of patients with PMF, highlighting different aspects of this disease, and evaluating the effectiveness of HSCT for the treatment of this disorder. Update of clinical data, hematological features, molecular studies, treatment and final outcome of four children diagnosed with VPS 45-associated PMF of infancy. The patients described had clinical and hematological findings consistent with MF. Molecular studies showed that all patients were homozygous for the Thr224Asn mutation in the VPS 45 gene. HSCT was carried out in three patients and was successful in two. VPS 45-associated MF is a novel primary immune deficiency that can be successfully corrected by HSCT if applied early in the course of disease using appropriate conditioning. The diagnosis of VPS 45-associated PMF should be considered in all children presenting with SCN with subsequent development of pancytopenia. Long-term follow-up of these patients is necessary to identify extra-hematological manifestations of VPS45 deficiency.read more
Citations
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Lessons learned from the study of human inborn errors of innate immunity.
Giorgia Bucciol,Leen Moens,Barbara Bosch,Xavier Bossuyt,Jean-Laurent Casanova,Anne Puel,Isabelle Meyts +6 more
TL;DR: Inborn errors of innate immunity that have been recently discovered or clarified are reviewed and the immunologic implications of these errors are highlighted.
Journal ArticleDOI
Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies
Peer Arts,Peer Arts,Annet Simons,Mofareh AlZahrani,Elanur Yilmaz,Elanur Yilmaz,Eman AlIdrissi,Koen J. van Aerde,Njood Alenezi,Hamza A. AlGhamdi,Hadeel A. AlJubab,Abdulrahman Al-Hussaini,Fahad AlManjomi,Alaa B. Alsaad,Badr Alsaleem,Abdulrahman A. Andijani,Ali Asery,Walid Ballourah,Chantal P. Bleeker-Rovers,Marcel van Deuren,Michiel van der Flier,Michiel van der Flier,Erica H. Gerkes,Christian Gilissen,Murad K. Habazi,Jayne Y. Hehir-Kwa,Stefanie S. V. Henriet,Esther P A H Hoppenreijs,Sarah Hortillosa,Chantal Kerkhofs,Riikka Keski-Filppula,Riikka Keski-Filppula,Stefan H. Lelieveld,Khurram Lone,M.A. MacKenzie,Arjen R. Mensenkamp,Jukka S. Moilanen,Jukka S. Moilanen,Marcel R. Nelen,Jaap ten Oever,Judith Potjewijd,Pieter van Paassen,Janneke H M Schuurs-Hoeijmakers,Anna Simon,Tomasz Stokowy,Maartje van de Vorst,Maaike Vreeburg,Anja Wagner,Gijs Th. J. van Well,Dimitra Zafeiropoulou,Evelien Zonneveld-Huijssoon,Joris A. Veltman,Joris A. Veltman,Wendy A. G. van Zelst-Stams,Eissa Faqeih,Frank L. van de Veerdonk,Mihai G. Netea,Alexander Hoischen +57 more
TL;DR: The clinical utility and diagnostic yield for a heterogeneous group of 254 consecutively referred PID patients from 249 families is reported, with exome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients.
Journal ArticleDOI
Myeloproliferative neoplasms in children
TL;DR: Particular attention will be given to pediatric PMF, as it is the only disorder of this group that is observed in infants and young children, and in many ways appears to be a unique entity compared to adult PMF.
Journal ArticleDOI
Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia
Ehud Even-Or,Adeeb Naser Eddin,Bella Shadur,Bella Shadur,Bella Shadur,Yael Dinur Schejter,Mohammad Najajreh,Orly Zelig,Irina Zaidman,Polina Stepensky +9 more
TL;DR: A pediatric patient with primary myelofibrosis of infancy caused by VPS45 protein deficiency, who developed severe refractory hemolytic anemia and immune‐mediated thrombocytopenia 3 months following HSCT is presented.
Journal ArticleDOI
Severe congenital neutropenia with neurological impairment due to a homozygous VPS45 p.E238K mutation: A case report suggesting a genotype-phenotype correlation.
Ilse Meerschaut,Victoria Bordon,Catharina Dhooge,Patricia Delbeke,Arnaud Vanlander,Amos J. Simon,Christoph Klein,R. Frank Kooy,Raz Somech,Bert Callewaert +9 more
TL;DR: The findings delineate the phenotype and indicate a possible genotype–phenotype correlation for neurological involvement in a girl with SCN and neurological impairment harboring a homozygous p.E238K mutation in VPS45.
References
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Journal ArticleDOI
A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Robert Kralovics,Francesco Passamonti,Andreas Buser,Soon Siong Teo,Ralph Tiedt,Jakob Passweg,André Tichelli,Mario Cazzola,Radek C. Skoda +8 more
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DIPSS Plus: A Refined Dynamic International Prognostic Scoring System for Primary Myelofibrosis That Incorporates Prognostic Information From Karyotype, Platelet Count, and Transfusion Status
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Journal ArticleDOI
A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment)
Francesco Passamonti,Francisco Cervantes,Alessandro M. Vannucchi,Enrica Morra,Elisa Rumi,Arturo Pereira,Paola Guglielmelli,Ester Pungolino,Marianna Caramella,Margherita Maffioli,Cristiana Pascutto,Mario Lazzarino,Mario Cazzola,Ayalew Tefferi +13 more
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Journal ArticleDOI
Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation
Nicolaus Kröger,Ernst Holler,Guido Kobbe,Martin Bornhäuser,Rainer Schwerdtfeger,Herrad Baurmann,Arnon Nagler,Wolfgang Bethge,Matthias Stelljes,Lutz Uharek,Hannes Wandt,Andreas Burchert,Paolo Corradini,Jörg Schubert,Martin Kaufmann,Peter Dreger,Gerald Wulf,Hermann Einsele,Tatjana Zabelina,Hans Michael Kvasnicka,Jürgen Thiele,Ronald Brand,Axel R. Zander,Dietger Niederwieser,Theo de Witte +24 more
TL;DR: A prospective multicenter phase 2 trial to determine efficacy of a busulfan-based reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors found that age older than 55 years and human leukocyte antigen-mismatched donor remained significant factors for survival.
Journal ArticleDOI
Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and management
TL;DR: Primary myelofibrosis is a myeloproliferative neoplasm characterized by stem cell‐derived clonal myelOProliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.
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