Acute myeloid leukemia or myelodysplastic syndrome with chromosome 17 abnormalities and long-term outcomes with or without hematopoietic stem cell transplantation

Britt, Alec; Mohyuddin, Ghulam Rehman; McClune, Brian; Singh, Anurag K.; Lin, Tara L.; Ganguly, Siddhartha; Abhyankar, Sunil; Shune, Leyla; McGuirk, Joseph P.; Skikne, Barry S.; Godwin, Andrew K.; Pessetto, Ziyan Y.; Golem, Shivani; Divine, Clint; Dias, Ajoy

doi:10.1016/j.leukres.2020.106402

Cited by 17 publications

(15 citation statements)

References 33 publications

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“…However, the presence of the TP53 mutation in AML or MDS is associated with a high risk of relapse pretransplant, and is the main cause of death following transplantation ( Table 4 ). A retrospective analysis of 30 patients who underwent aHSCT for AML (n = 19) or MDS (n = 11) with chromosome 17 abnormalities, reported a poor outcome for patients with the TP53 mutation [ 69 ]. Patients experienced short relapse-free survival, with a median relapse-free survival of 6- and 4-months post-transplant for the AML and MDS patients, respectively, ( p > 0.5).…”

Section: Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

How I Treat TP53-Mutated Acute Myeloid Leukemia and Myelodysplastic Syndromes

Loschi

Fenaux

Cluzeau

2022

Cancers

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TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are among the myeloid malignancies with the poorest prognosis. In this review, we analyze the prognosis of these two diseases, focussing particularly on the extent of the mono or biallelic mutation status of TP53 mutation, which is largely correlated with cytogenetic complexity. We discuss the possible/potential improvement in outcome based on recent results obtained with new drugs (especially eprenetapopt and magrolimab). We also focus on the impact of allogeneic hematopoietic stem cell transplantation (aHSCT) including post aHSCT treatment.

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Section: Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

How I Treat TP53-Mutated Acute Myeloid Leukemia and Myelodysplastic Syndromes

Loschi

Fenaux

Cluzeau

2022

Cancers

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“…The Brit et Al. 36 study reported the long-term outcomes of 98 patients with AML or MDS with chromosome 17 abnormalities, 55 had de novo MDS/AML, and 43 had secondary MDS/AML. There were no differences between the two groups regarding the presence of monosomal karyotype (69.1 % versus 67.4 %; p = 0.51).…”

Section: Chromosome 17 Abnormalitiesmentioning

confidence: 99%

De Novo and Therapy-Related Myelodysplastic Syndromes: Analogies and Differences

Leone¹,

Fabiani²,

Voso

2022

Mediterr J Hematol Infect Dis

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The aim of our review has been to give an appropriate idea of analogies and differences between primitive MDS (p-MDS) and t-MDS throughout an accurate reviewing of English peer-reviewed literature focusing on clinical, cytogenetic, epigenetic, and somatic mutation features of these two groups of diseases. Therapy-related MDS (t-MDS) are classified by WHO together with therapy-related acute myeloid leukemia (t-AML) in the same group, named therapy-related myeloid neoplasm. However, in clinical practice, the diagnosis of t-MDS is made with the same criteria as for primitive MDS (p-MDS), and the only difference is a previous non-myeloid neoplasm. The prognosis and the consequent therapy can be established following the same criteria as for p-MDS, and the therapy is generally decided using the same criteria. We stress the possible difference in cytogenetics, mutations, and epigenetics to distinguish the two forms. Actually, there is no marker specific for t-MDS either in cytogenetics, epigenetics, or mutations; however, some alterations are also frequent in t-MDS and, in general, they induce a poorer prognosis. So, the high-risk forms in t-MDS are prevalent. The present literature data suggest classifying the t-MDS as a subgroup of MDS and introducing some parameters to evaluate the probability of previous therapy in inducing MDS. An important issue remains the patient’s fitness, which strongly influences the outcome. Keywords: MDS, t-MDS- Cytogenetics, Mutation, Epigenetics.

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“…39 Given that the function of immune subsets can dictate clinical response to therapies in bone marrow failure syndromes, 40 it is tempting to speculate that an initial allogeneic immune response may be abrogated in such immunosuppressive/immune-evasive environments, leading to increased relapse rates posttransplant. [41][42][43] A high dose of cytotoxic NK cells within the stem cell graft has been shown to be associated with dramatically reduced relapse rates posttransplant. 44 In addition, persistence of disease-specific mutations 30 days posttransplant in patients allografted for myelodysplasia is associated with an increased risk of relapse.…”

Section: How Does Targeted Molecular Profiling Permit Optimization Of...mentioning

confidence: 99%

The Evolving Role of Allogeneic Stem Cell Transplant in the Era of Molecularly Targeted Agents

Kinsella

Craddock

2022

Cancer J

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Allogeneic stem cell transplantation (allo-SCT) is an increasingly important treatment strategy in fit adults with acute myeloid leukemia (AML). Increased donor availability and a steady reduction in transplantrelated mortality (TRM) over the last 2 decades have transformed access to the curative potential of allo-SCT. The identification of patients with AML in first complete remission who will benefit from allo-SCT requires a dynamic assessment of the risk of disease relapse and TRM. Increased accuracy in predicting both relapse risk and transplant toxicity has allowed recommendations for allo-SCT to become increasingly personalized. Notwithstanding its now central position in the treatment algorithm of patients with AML, there, however, has been little progress in reducing the main cause of transplant failure, which remains disease relapse. Novel molecularly targeted therapies have the potential to augment the curative potential of nontransplant therapies, and this may influence the proportion of newly diagnosed fit patients deemed to be allomandatory. At the same time, the ability of such therapies to improve transplant outcomes, either by reducing TRM or the risk of relapse, has the potential to further embed allo-SCT as a key therapeutic modality in AML.

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Acute myeloid leukemia or myelodysplastic syndrome with chromosome 17 abnormalities and long-term outcomes with or without hematopoietic stem cell transplantation

Cited by 17 publications

References 33 publications

How I Treat TP53-Mutated Acute Myeloid Leukemia and Myelodysplastic Syndromes

How I Treat TP53-Mutated Acute Myeloid Leukemia and Myelodysplastic Syndromes

De Novo and Therapy-Related Myelodysplastic Syndromes: Analogies and Differences

The Evolving Role of Allogeneic Stem Cell Transplant in the Era of Molecularly Targeted Agents

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