Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial
Uwe Platzbecker,Martin Wermke,Jörgen Radke,Uta Oelschlaegel,F Seltmann,Alexander Kiani,Ina-Maria Klut,Holger Knoth,Christoph Röllig,Johannes Schetelig,Brigitte Mohr,Xina Graehlert,Gerhard Ehninger,Martin Bornhäuser,Christian Thiede +14 more
Reads0
Chats0
TLDR
In this article, the authors evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34+ blood cells to pre-empt relapse in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT).Abstract:
This study evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34+ blood cells to pre-empt relapse in patients with CD34+ myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). At a median of 169 days after HSCT, 20/59 prospectively screened patients experienced a decrease of CD34+ donor chimerism to <80% and received four azacitidine cycles (75 mg/m2/day for 7 days) while in complete hematologic remission. A total of 16 patients (80%) responded with either increasing CD34+ donor chimerism to ⩾80% (n=10; 50%) or stabilization (n=6; 30%) in the absence of relapse. Stabilized patients and those with a later drop of CD34+ donor chimerism to <80% after initial response were eligible for subsequent azacitidine cycles. A total of 11 patients (55%) received a median of 4 (range, 1–11) additional cycles. Eventually, hematologic relapse occurred in 13 patients (65%), but was delayed until a median of 231 days (range, 56–558) after initial decrease of CD34+ donor chimerism to <80%. In conclusion, pre-emptive azacitidine treatment has an acceptable safety profile and can substantially prevent or delay hematologic relapse in patients with MDS or AML and MRD after allogeneic HSCT.read more
Citations
More filters
Journal ArticleDOI
Acute myeloid leukemia: 2013 update on risk-stratification and management.
TL;DR: It is likely that many different mutations, epigenetic aberrations, or abnormalities in micro RNA expression can produce the same morphologic disease with these differences responsible for the very variable response to therapy, which is AMLs principal feature.
Journal ArticleDOI
Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel
Theo de Witte,David G. Bowen,Marie Robin,Luca Malcovati,Dietger Niederwieser,Ibrahim Yakoub-Agha,Ghulam J. Mufti,Pierre Fenaux,Guillermo Sanz,Rodrigo Martino,Emilio Paolo Alessandrino,Francesco Onida,Argiris Symeonidis,Jakob Passweg,Guido Kobbe,Arnold Ganser,Uwe Platzbecker,Jürgen Finke,Michel van Gelder,Arjan A. van de Loosdrecht,Per Ljungman,Reinhard Stauder,Liisa Volin,H. Joachim Deeg,H. Joachim Deeg,Corey Cutler,Wael Saber,Richard E. Champlin,Sergio Giralt,Claudio Anasetti,Nicolaus Kröger +30 more
TL;DR: Recommendations for allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) and prophylactic donor lymphocyte infusion (DLI) strategies are recommended in patients at high risk of relapse after HSCT.
Journal ArticleDOI
Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial.
Uwe Platzbecker,Jan Moritz Middeke,Katja Sockel,Regina Herbst,Dominik Wolf,Dominik Wolf,Claudia D. Baldus,Uta Oelschlägel,Anke Mütherig,Lars Fransecky,Richard Noppeney,Gesine Bug,Katharina Götze,Alwin Krämer,Tilmann Bochtler,Matthias Stelljes,Christoph Groth,Antje Schubert,Marika Mende,Friedrich Stölzel,Christine Borkmann,A.S. Kubasch,Malte von Bonin,Hubert Serve,Mathias Hänel,Ulrich Dührsen,Johannes Schetelig,C. Röllig,Michael Kramer,Gerhard Ehninger,Martin Bornhäuser,Christian Thiede +31 more
TL;DR: This study suggests that continuous MRD negativity during regular MRD monitoring might be prognostic for patient outcomes and pre-emptive therapy with azacitidine can prevent or substantially delay haematological relapse in MRD-positive patients with MDS or AML who are at high risk of relapse.
Journal ArticleDOI
Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation
Cristina Toffalori,Laura Zito,Valentina Gambacorta,Michela Riba,Giacomo Oliveira,Giacomo Oliveira,Gabriele Bucci,Matteo Barcella,Orietta Spinelli,Raffaella Greco,Lara Crucitti,Nicoletta Cieri,Nicoletta Cieri,Maddalena Noviello,Francesco Manfredi,Elisa Montaldo,Renato Ostuni,Matteo Maria Naldini,Bernhard Gentner,Miguel Waterhouse,Robert Zeiser,Jürgen Finke,Maher Hanoun,Dietrich W. Beelen,Ivana Gojo,Leo Luznik,Masahiro Onozawa,Takanori Teshima,Raynier Devillier,Didier Blaise,Constantijn J.M. Halkes,Marieke Griffioen,Matteo Carrabba,Massimo Bernardi,Jacopo Peccatori,Cristina Barlassina,Elia Stupka,Elia Stupka,Dejan Lazarevic,Giovanni Tonon,Alessandro Rambaldi,Davide Cittaro,Chiara Bonini,Katharina Fleischhauer,Fabio Ciceri,Luca Vago +45 more
TL;DR: The results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies.
Journal ArticleDOI
Relation of Clinical Response and Minimal Residual Disease and Their Prognostic Impact on Outcome in Acute Myeloid Leukemia
Xueyan Chen,Hu Xie,Brent L. Wood,Roland B. Walter,John M. Pagel,Pamela S. Becker,Vicky Sandhu,Janis L. Abkowitz,Frederick R. Appelbaum,Elihu H. Estey +9 more
TL;DR: Post-therapy parameters including MRD status and response are important independent prognostic factors for outcome in patients with AML achieving remission, and should play important, and perhaps dominant, roles in planning postinduction therapy.
References
More filters
Journal ArticleDOI
The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
James W. Vardiman,Juergen Thiele,Daniel A. Arber,Richard D. Brunning,Michael J. Borowitz,Anna Porwit,Nancy L. Harris,Michelle M. Le Beau,Eva Hellström-Lindberg,Ayalew Tefferi,Clara D. Bloomfield +10 more
TL;DR: The classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.
Journal ArticleDOI
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet.
Hartmut Döhner,Elihu H. Estey,Sergio Amadori,Frederick R. Appelbaum,Thomas Büchner,Alan Kenneth Burnett,Hervé Dombret,Pierre Fenaux,David Grimwade,Richard A. Larson,Francesco Lo-Coco,Tomoki Naoe,Dietger Niederwieser,Gert J. Ossenkoppele,Miguel A. Sanz,Jorge Sierra,Martin S. Tallman,Bob Löwenberg,Clara D. Bloomfield +18 more
TL;DR: An international expert panel is provided to provide updated evidence- and expert opinion-based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials.
Journal ArticleDOI
Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.
Pierre Fenaux,Ghulam J. Mufti,Eva Hellström-Lindberg,Valeria Santini,Carlo Finelli,Aristoteles Giagounidis,Robert Schoch,Norbert Gattermann,Guillermo Sanz,Alan F. List,Steven D. Gore,John F. Seymour,John M. Bennett,John C. Byrd,Jay Backstrom,Linda Zimmerman,David McKenzie,C.L. Beach,Lewis R. Silverman +18 more
TL;DR: Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care.
Journal ArticleDOI
The World Health Organization (WHO) classification of the myeloid neoplasms.
TL;DR: The purpose of this communication is to outline briefly the WHO classification of malignant myeloid diseases, to draw attention to major differences between it and antecedent classification schemes, and to provide the rationale for those differences.
Journal ArticleDOI
Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B
Lewis R. Silverman,Erin P. Demakos,Bercedis L. Peterson,Alice B. Kornblith,Jimmie C. Holland,Rosalie Odchimar-Reissig,Richard Stone,Douglas A. Nelson,Bayard L. Powell,Carlos M. DeCastro,John Ellerton,Richard A. Larson,Charles A. Schiffer,James F. Holland +13 more
TL;DR: Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care.
Related Papers (5)
Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.
Pierre Fenaux,Ghulam J. Mufti,Eva Hellström-Lindberg,Valeria Santini,Carlo Finelli,Aristoteles Giagounidis,Robert Schoch,Norbert Gattermann,Guillermo Sanz,Alan F. List,Steven D. Gore,John F. Seymour,John M. Bennett,John C. Byrd,Jay Backstrom,Linda Zimmerman,David McKenzie,C.L. Beach,Lewis R. Silverman +18 more
Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
Hartmut Döhner,Elihu H. Estey,David Grimwade,Sergio Amadori,Frederick R. Appelbaum,Thomas Büchner,Hervé Dombret,Benjamin L. Ebert,Pierre Fenaux,Richard A. Larson,Ross L. Levine,Francesco Lo-Coco,Tomoki Naoe,Dietger Niederwieser,Gert J. Ossenkoppele,Miguel A. Sanz,Jorge Sierra,Martin S. Tallman,Hwei-Fang Tien,Andrew H. Wei,Andrew H. Wei,Bob Löwenberg,Clara D. Bloomfield +22 more
Assessment of Minimal Residual Disease in Standard-Risk AML.
Adam Ivey,Robert Kerrin Hills,Michael A. Simpson,Jelena V. Jovanovic,Amanda F. Gilkes,Angela Grech,Yashma Patel,Neesa Bhudia,Hassan Farah,Joanne Mason,Kerry Wall,Susanna Akiki,Mike Griffiths,Ellen Solomon,Frank McCaughan,David C. Linch,Rosemary E. Gale,Paresh Vyas,Sylvie D. Freeman,Nigel H. Russell,Alan Kenneth Burnett,David Grimwade +21 more