von Rong Fang ; Marco Düring ; Felix J. Bode ; Sebastian Stösser ; Julius Nicolai Meißner ; Peter Hermann ; Thomas Liman ; Christian H. Nolte ; Lucia Kerti ; Benno Ikenberg ; Kathleen Bernkopf ; Wenzel Glanz ; Daniel Janowitz ; Michael Wagner ; Katja Neumann ; Oliver Speck ; Emrah Düzel ; Benno Gesierich ; Anna Dewenter ; Annika Spottke ; Karin Waegemann ; Michael Görtler ; Silke Wunderlich ; Inga Zerr ; Gabor Petzold ; Matthias Endres ; Marios K. Georgakis ; Martin Dichgans
von Peter Hietz ; Katrin Wagner ; Flavio Nunes Ramos ; Juliano Sarmento Cabral ; Claudia Agudelo ; Ana María Benavides ; Manuel Jesús Cach-Pérez ; Catherine L. Cardelús ; Nahlleli Chilpa Galván ; Lucas Erickson Nascimento da Costa ; Rodolfo De Paula Oliveira ; Helena J. R. Einzmann ; Rafael De Paiva Farias ; Valeria Guzman-Jacob ; Jens Kattge ; Michael Kessler ; Catherine Kirby ; Holger Kreft ; Thorsten Krömer ; Jamie Males ; Samuel Monsalve Correa ; Maria Moreno-Chacón ; Gunnar Petter ; Casandra Reyes-García ; Alfredo Saldaña ; David Schellenberger Costa ; Amanda Taylor ; Noé Velázquez Rosas ; Wolfgang Wanek ; Carrie L. Woods ; Gerhard Zotz
Online first: 8 January 2021 ; Gesehen am 16.07.2021
First-line therapy for younger patients with peripheral T-cell non-Hodgkin lymphoma (T-NHL) consists of 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide (CHOEP), consolidated by high-dose therapy and autologous stem cell transplantation (auto-SCT). We hypothesized that allogeneic stem cell transplantation (allo-SCT) could improve outcomes. 104 patients with peripheral T-cell non-Hodgkin lymphoma, except ALK+ anaplastic large cell lymphoma, 18 to 60 years, all stages, and all age adjusted International Prognostic Index scores, except 0 and stage I, were randomized to 4 cycles of CHOEP and 1 cycle of dexamethasone, cytosine-arabinoside, and platinum (DHAP) followed by high-dose therapy and auto-SCT or myeloablative conditioning and allo-SCT. The primary end point was event-free survival (EFS) at 3 years. After a median follow-up of 42 months, the 3-year EFS after allo-SCT was 43%, as compared with 38% after auto-SCT. Overall survival at 3 years was 57% vs 70% after allo- or auto-SCT, without significant differences between treatment arms. None of the 21 responding patients proceeding to allo-SCT relapsed, as opposed to 13 of 36 patients (36%) proceeding to auto-SCT. Eight of 26 patients (31%) and none of 41 patients died of transplant-related toxicity after allo- and auto-SCT, respectively. The strong graft-versus-lymphoma effect after allo-SCT was counterbalanced by transplant-related mortality. This trial is registered at www.clinicaltrials.gov as #NCT00984412.
Blood Washington, DC : American Society of Hematology, 1946 137(2021), 19 vom: 13. Mai, Seite 2646-2656 Online-Ressource
von Elodie M. Richard ; Somayeh Bakhtiari ; Ashley P. L. Marsh ; Rauan Kaiyrzhanov ; Matias Wagner ; Sheetal Shetty ; Alex Pagnozzi ; Sandra M. Nordlie ; Brandon S. Guida ; Patricia Cornejo ; Helen Magee ; James Liu ; Bethany Y. Norton ; Richard I. Webster ; Lisa Worgan ; Hakon Hakonarson ; Jiankang Li ; Yiran Guo ; Mahim Jain ; Alyssa Blesson ; Lance H. Rodan ; Mary-Alice Abbott ; Anne Comi ; Julie S. Cohen ; Bader Alhaddad ; Thomas Meitinger ; Dominic Lenz ; Andreas Ziegler ; Urania Kotzaeridou ; Theresa Brunet ; Anna Chassevent ; Constance Smith-Hicks ; Joseph Ekstein ; Tzvi Weiden ; Andreas Hahn ; Nazira Zharkinbekova ; Peter Turnpenny ; Arianna Tucci ; Melissa Yelton ; Rita Horvath ; Serdal Gungor ; Semra Hiz ; Yavuz Oktay ; Hanns Lochmuller ; Marcella Zollino ; Manuela Morleo ; Giuseppe Marangi ; Vincenzo Nigro ; Annalaura Torella ; Michele Pinelli ; Simona Amenta ; Ralf A. Husain ; Benita Grossmann ; Marion Rapp ; Claudia Steen ; Iris Marquardt ; Mona Grimmel ; Ute Grasshoff ; Christoph Korenke ; Marta Owczarek-Lipska ; John Neidhardt ; Francesca Clementina Radio ; Cecilia Mancini ; Dianela Judith Claps Sepulveda ; Kirsty McWalter ; Amber Begtrup ; Amy Crunk ; Maria J. Guillen Sacoto ; Richard Person ; Rhonda E. Schnur ; Maria Margherita Mancardi ; Florian Kreuder ; Pasquale Striano ; Federico Zara ; Wendy K. Chung ; Warren A. Marks ; Clare L. van Eyk ; Dani L. Webber ; Mark A. Corbett ; Kelly Harper ; Jesia G. Berry ; Alastair H. MacLennan ; Jozef Gecz ; Marco Tartaglia ; Vincenzo Salpietro ; John Christodoulou ; Jan Kaslin ; Sergio Padilla-Lopez ; Kaya Bilguvar ; Alexander Munchau ; Zubair M. Ahmed ; Robert B. Hufnagel ; Michael C. Fahey ; Reza Maroofian ; Henry Houlden ; Heinrich Sticht ; Shrikant M. Mane ; Aboulfazl Rad ; Barbara Vona ; Sheng Chih Jin ; Tobias B. Haack ; Christine Makowski ; Yoel Hirsch ; Saima Riazuddin ; Michael C. Kruer
Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.
The American journal of human genetics New York, NY [u.a.] : Cell Press, 1949 108(2021), 10, Seite 2006-2016
