Literature DB >> 32362171

Clinical outcomes and characteristics of patients with TP53-mutated acute myeloid leukemia or myelodysplastic syndromes: a single center experience.

Jan Philipp Bewersdorf1, Rory M Shallis1, Lohith Gowda1, Wei Wei2, Karl Hager3, Iris Isufi1, Tae Kon Kim1,4, Manoj M Pillai1, Stuart Seropian1, Nikolai A Podoltsev1,5, Steven D Gore1,5, Alexa J Siddon3,6, Amer M Zeidan1,5.   

Abstract

Mutations in the tumor suppressor gene TP53 are detected in 5-10% of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes. TP53 mutations have been associated with complex karyotypes, therapy-related malignancies, lower response rates to cytotoxic chemotherapy, and an overall adverse prognosis. In this single-center retrospective study, we analyzed the clinicopathologic characteristics and outcomes of 83 patients with TP53-mutated myeloid malignancies treated at Yale Cancer Center between 9/2015 and 5/2019. Complex karyotypes (n = 75; 90%) and therapy-related malignancies (n = 32; 39%) were common. Median overall survival (OS) was 7.6 months. Intensive chemotherapy did not improve OS compared to lower-intensity treatment for AML patients. Patients who underwent allogeneic hematopoietic stem cell transplant (alloHSCT) had a significantly longer median OS, despite relatively limited follow-up. In conclusion, our data confirm the limited efficacy of intensive chemotherapy approaches for TP53-mutated patients with myeloid neoplasms and suggest that a minority of patients achieve long-term survival with alloHSCT.

Entities:  

Keywords:  AML; Acute myeloid leukemia; MDS; TP53; myelodysplastic syndrome; stem cell transplant

Mesh:

Substances:

Year:  2020        PMID: 32362171      PMCID: PMC7603787          DOI: 10.1080/10428194.2020.1759051

Source DB:  PubMed          Journal:  Leuk Lymphoma        ISSN: 1026-8022


  47 in total

1.  Outcome of patients with abnl(17p) acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

Authors:  Jan M Middeke; Min Fang; Jan J Cornelissen; Brigitte Mohr; Frederick R Appelbaum; Michael Stadler; Jaime Sanz; Herrad Baurmann; Gesine Bug; Kerstin Schäfer-Eckart; Ute Hegenbart; Tilmann Bochtler; Christoph Röllig; Friedrich Stölzel; Roland B Walter; Gerhard Ehninger; Martin Bornhäuser; Bob Löwenberg; Johannes Schetelig
Journal:  Blood       Date:  2014-03-20       Impact factor: 22.113

Review 2.  Therapy-related myelodysplastic syndromes, or are they?

Authors:  Abdallah Abou Zahr; Ami M Kavi; Sudipto Mukherjee; Amer M Zeidan
Journal:  Blood Rev       Date:  2016-11-24       Impact factor: 8.250

3.  Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes.

Authors:  D A Sallman; R Komrokji; C Vaupel; T Cluzeau; S M Geyer; K L McGraw; N H Al Ali; J Lancet; M J McGinniss; S Nahas; A E Smith; A Kulasekararaj; G Mufti; A List; J Hall; E Padron
Journal:  Leukemia       Date:  2015-10-30       Impact factor: 11.528

Review 4.  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

5.  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.

Authors:  Uwe Platzbecker; Jan Moritz Middeke; Katja Sockel; Regina Herbst; Dominik Wolf; Claudia D Baldus; Uta Oelschlägel; Anke Mütherig; Lars Fransecky; Richard Noppeney; Gesine Bug; Katharina S Götze; Alwin Krämer; Tilmann Bochtler; Matthias Stelljes; Christoph Groth; Antje Schubert; Marika Mende; Friedrich Stölzel; Christine Borkmann; Anne Sophie Kubasch; Malte von Bonin; Hubert Serve; Mathias Hänel; Ulrich Dührsen; Johannes Schetelig; Christoph Röllig; Michael Kramer; Gerhard Ehninger; Martin Bornhäuser; Christian Thiede
Journal:  Lancet Oncol       Date:  2018-11-12       Impact factor: 41.316

Review 6.  Dysfunctional diversity of p53 proteins in adult acute myeloid leukemia: projections on diagnostic workup and therapy.

Authors:  Miron Prokocimer; Alina Molchadsky; Varda Rotter
Journal:  Blood       Date:  2017-06-12       Impact factor: 22.113

7.  Distinct mutation spectrum, clinical outcome and therapeutic responses of typical complex/monosomy karyotype acute myeloid leukemia carrying TP53 mutations.

Authors:  Garret M K Leung; Chunxiao Zhang; Nelson K L Ng; Ning Yang; Stephen S Y Lam; Chun H Au; Tsun L Chan; Edmond S K Ma; Sze P Tsui; Ho W Ip; Jason C C So; Margaret H L Ng; Kelvin C K Cheng; Kit F Wong; Lisa L P Siu; Sze F Yip; Shek Y Lin; June S M Lau; Tsan H Luk; Harold K K Lee; Chi K Lau; Bonnie Kho; Yok L Kwong; Anskar Y H Leung
Journal:  Am J Hematol       Date:  2019-04-16       Impact factor: 10.047

8.  TP53 mutation variant allele frequency is a potential predictor for clinical outcome of patients with lower-risk myelodysplastic syndromes.

Authors:  Monika Belickova; Jitka Vesela; Anna Jonasova; Barbora Pejsova; Hana Votavova; Michaela Dostalova Merkerova; Zuzana Zemanova; Jana Brezinova; Dana Mikulenkova; Marie Lauermannova; Jan Valka; Kyra Michalova; Radana Neuwirtova; Jaroslav Cermak
Journal:  Oncotarget       Date:  2016-06-14

9.  Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT).

Authors:  Xavier Poiré; Myriam Labopin; Johan Maertens; Ibrahim Yakoub-Agha; Didier Blaise; Norbert Ifrah; Gérard Socié; Tobias Gedde-Dhal; Nicolaas Schaap; Jan J Cornelissen; Stéphane Vigouroux; Jaime Sanz; Lucienne Michaux; Jordi Esteve; Mohamad Mohty; Arnon Nagler
Journal:  J Hematol Oncol       Date:  2017-01-18       Impact factor: 17.388

10.  Mutational processes shape the landscape of TP53 mutations in human cancer.

Authors:  Andrew O Giacomelli; Xiaoping Yang; Robert E Lintner; James M McFarland; Marc Duby; Jaegil Kim; Thomas P Howard; David Y Takeda; Seav Huong Ly; Eejung Kim; Hugh S Gannon; Brian Hurhula; Ted Sharpe; Amy Goodale; Briana Fritchman; Scott Steelman; Francisca Vazquez; Aviad Tsherniak; Andrew J Aguirre; John G Doench; Federica Piccioni; Charles W M Roberts; Matthew Meyerson; Gad Getz; Cory M Johannessen; David E Root; William C Hahn
Journal:  Nat Genet       Date:  2018-09-17       Impact factor: 38.330

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  2 in total

Review 1.  Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?

Authors:  Rory M Shallis; Jan P Bewersdorf; Maximilian F Stahl; Stephanie Halene; Amer M Zeidan
Journal:  Cancers (Basel)       Date:  2022-05-14       Impact factor: 6.575

2.  TP53-mutant myelodysplastic syndrome and acute myeloid leukemia: the black hole of hematology.

Authors:  Shyam A Patel; Jan Cerny
Journal:  Blood Adv       Date:  2022-03-22
  2 in total

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