Literature DB >> 34750086

Nonmyeloablative Allogeneic Transplantation With Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia With IDH Mutations: A Single Center Experience.

Alexander Ambinder1, Matthew Smith2, Hua-Ling Tsai2, Ravi Varadhan2, Amy DeZern2, William Dalton2, Christian Gocke2, Jonathan Webster2, Lukasz Gondek2, Ivana Gojo2, Syed Abbas Ali2, Carol Ann Huff2, Lode Swinnen2, Nina Wagner-Johnston2, Margaret Showel2, Gabrielle Prince2, Ivan Borrello2, Javier Bolaños-Meade2, Leo Luznik2, Tania Jain2, Philip Imus2, Ephraim Fuchs2, Richard Ambinder2, Douglas E Gladstone2, Mark Levis2, Richard Jones2, Gabriel Ghiaur2, B Douglas Smith2.   

Abstract

INTRODUCTION: Mutations in the IDH1 or IDH2 genes are detected in approximately 20% of cases of acute myeloid leukemia (AML). Few studies have examined the impact of IDH mutations in AML on allogeneic bone marrow transplant (alloBMT) outcomes. PATIENTS AND METHODS: In this single center study, alloBMT outcomes for 61 patients with IDH-mutated (mIDH) AML were compared to those for 146 patients with IDH-wildtype (wtIDH) AML.
RESULTS: Patients with mIDH AML had a 2-year overall survival (OS) of 85% (95% CI 76%-95%), 2-year relapse free survival (RFS) of 71% (95% CI 59%-85%), 1-year cumulative incidence of relapse (CIR) of 14% (95% CI 5%-23%) and a 1-year cumulative incidence of transplant related mortality (CITRM) of 3% (95% CI 0%-8%). Patients with wtIDH had a 2-year OS of 61% (95% CI 53%-70%), 2-year RFS of 58% (95% CI 50%-67%), 1-year CIR of 27% (95% CI 20%-35%), and a 1-year CITRM of 9% (95% CI 5%-14%). In a univariate analysis cox-proportional hazard model, mIDH was associated with significantly better OS (HR 0.52, 95% CI 0.29-0.96) and a trend toward better RFS (HR 0.60, 95% CI 0.35-1.01). After controlling for donor age, diagnosis, and ELN risk category, mIDH was associated with a nonsignificantly improved OS (HR 0.54, 95% CI 0.29-1.01) and RFS (HR 0.67, 95% CI 0.39-1.15).
CONCLUSION: Among patients with mIDH AML, patients who received a peritransplant IDH inhibitor had improved OS (P = .03) compared to those who did not, but there was no detectable difference for RFS (P = .29).
Copyright © 2021 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Acute myeloid leukemia; Bone marrow transplant; Isocitrate dehydrogenase inhibitors; Isocitrate dehydrogenase mutations; Outcomes

Mesh:

Substances:

Year:  2021        PMID: 34750086      PMCID: PMC8977228          DOI: 10.1016/j.clml.2021.09.022

Source DB:  PubMed          Journal:  Clin Lymphoma Myeloma Leuk        ISSN: 2152-2669


  29 in total

Review 1.  Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

Authors:  Hartmut Döhner; Elihu 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 Sanz; Jorge Sierra; Martin S Tallman; Hwei-Fang Tien; Andrew H Wei; Bob Löwenberg; Clara D Bloomfield
Journal:  Blood       Date:  2016-11-28       Impact factor: 22.113

2.  Prognostic relevance of integrated genetic profiling in acute myeloid leukemia.

Authors:  Jay P Patel; Mithat Gönen; Maria E Figueroa; Hugo Fernandez; Zhuoxin Sun; Janis Racevskis; Pieter Van Vlierberghe; Igor Dolgalev; Sabrena Thomas; Olga Aminova; Kety Huberman; Janice Cheng; Agnes Viale; Nicholas D Socci; Adriana Heguy; Athena Cherry; Gail Vance; Rodney R Higgins; Rhett P Ketterling; Robert E Gallagher; Mark Litzow; Marcel R M van den Brink; Hillard M Lazarus; Jacob M Rowe; Selina Luger; Adolfo Ferrando; Elisabeth Paietta; Martin S Tallman; Ari Melnick; Omar Abdel-Wahab; Ross L Levine
Journal:  N Engl J Med       Date:  2012-03-14       Impact factor: 91.245

3.  Prognostic significance of IDH1 mutations in acute myeloid leukemia: a meta-analysis.

Authors:  Jian-Hua Feng; Xiao-Ping Guo; Yuan-Yuan Chen; Zhu-Jun Wang; Yu-Ping Cheng; Yong-Min Tang
Journal:  Am J Blood Res       Date:  2012-11-25

4.  Clinical guide to ABO-incompatible allogeneic stem cell transplantation.

Authors:  Garrett S Booth; Eric A Gehrie; Charles D Bolan; Bipin N Savani
Journal:  Biol Blood Marrow Transplant       Date:  2013-04-06       Impact factor: 5.742

5.  Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML.

Authors:  Courtney D DiNardo; Farhad Ravandi; Sam Agresta; Marina Konopleva; Koichi Takahashi; Tapan Kadia; Mark Routbort; Keyur P Patel; Sherry Pierce; Guillermo Garcia-Manero; Jorge Cortes; Hagop Kantarjian
Journal:  Am J Hematol       Date:  2015-08       Impact factor: 13.265

6.  IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.

Authors:  Guido Marcucci; Kati Maharry; Yue-Zhong Wu; Michael D Radmacher; Krzysztof Mrózek; Dean Margeson; Kelsi B Holland; Susan P Whitman; Heiko Becker; Sebastian Schwind; Klaus H Metzeler; Bayard L Powell; Thomas H Carter; Jonathan E Kolitz; Meir Wetzler; Andrew J Carroll; Maria R Baer; Michael A Caligiuri; Richard A Larson; Clara D Bloomfield
Journal:  J Clin Oncol       Date:  2010-04-05       Impact factor: 50.717

7.  Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value.

Authors:  Saman Abbas; Sanne Lugthart; François G Kavelaars; Anita Schelen; Jasper E Koenders; Annelieke Zeilemaker; Wim J L van Putten; Anita W Rijneveld; Bob Löwenberg; Peter J M Valk
Journal:  Blood       Date:  2010-06-10       Impact factor: 25.476

8.  Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study.

Authors:  Matthieu Duchmann; Jean-Baptiste Micol; Nicolas Duployez; Emmanuel Raffoux; Xavier Thomas; Jean-Pierre Marolleau; Thorsten Braun; Lionel Adès; Sylvain Chantepie; Emilie Lemasle; Céline Berthon; Jean-Valère Malfuson; Cécile Pautas; Juliette Lambert; Nicolas Boissel; Karine Celli-Lebras; Denis Caillot; Pascal Turlure; Norbert Vey; Arnaud Pigneux; Christian Recher; Christine Terré; Claude Gardin; Raphaël Itzykson; Claude Preudhomme; Hervé Dombret; Stéphane de Botton
Journal:  Blood       Date:  2021-05-20       Impact factor: 25.476

9.  Allogeneic Hematopoietic Cell Transplantation Outcomes in Patients Carrying Isocitrate Dehydrogenase Mutations.

Authors:  Amandeep Salhotra; Michelle Afkhami; Dongyun Yang; Sally Mokhtari; Milhan Telatar; Dongqing Gu; Raju K Pillai; Dennis D Weisenburger; Joyce Murata-Collins; Diana Weigel; Patricia Aoun; Ibrahim Aldoss; Monzr M Al Malki; Samer Khaled; Matthew Mei; Haris Ali; Ahmed Aribi; Elizabeth Budde; Karamjeet Sandhu; Margaret O'Donnell; David Snyder; Vinod Pullarkat; Stephen J Forman; Guido Marcucci; Ryotaro Nakamura; Anthony Stein
Journal:  Clin Lymphoma Myeloma Leuk       Date:  2019-04-26

Review 10.  What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer.

Authors:  Julie-Aurore Losman; William G Kaelin
Journal:  Genes Dev       Date:  2013-04-15       Impact factor: 12.890

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  1 in total

Review 1.  Maintenance therapy for AML after allogeneic HCT.

Authors:  Rahul K Nayak; Yi-Bin Chen
Journal:  Front Oncol       Date:  2022-08-09       Impact factor: 5.738

  1 in total

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