Molecular minimal residual disease negativity and decreased stem cell mobilization potential predict excellent outcome after autologous transplant in <i>NPM1</i> mutant acute myeloid leukemia

Benito, Alvaro de Santiago de; Jeker, Barbara; Gfeller, Eva; Porret, Naomi; Banz, Yara; Novak, Urban; Bacher, Ulrike; Pabst, Thomas

doi:10.3324/haematol.2019.216457

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…Autologous transplantation can potentially allow a selected group of patients, especially with low and potentially intermediate genetic risk, to avoid over-treatment with allogeneic transplantation, providing 50–60% probability of long-term LFS [74]. The recently published excellent outcomes of autologous transplantation in MRD negative patients with low or intermediate genetic risk [75,76,77,78] prompt re-evaluating the role of autologous transplantation in AML. In this regard, a group from China compared retrospectively autologous to allogeneic HSCT in AML patients with favorable or intermediate genetic risk [76].…”

Section: The Role Of Mrd In Hsct For Amlmentioning

confidence: 99%

The Role of Measurable Residual Disease (MRD) in Hematopoietic Stem Cell Transplantation for Hematological Malignancies Focusing on Acute Leukemia

Czyż

Nagler

2019

IJMS

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The significance of measurable residual disease (MRD) in hematopoietic stem cell transplantation (HSCT) is well recognized in different hematological malignancies, but the evidence indicate that pre-transplant MRD status is of particular importance in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In ALL, inadequate response at the level of MRD is a commonly accepted risk factor for relapse and thus an indication for allogeneic HSCT. Similarly, growing evidence from the literature strongly suggest that MRD detected by multiparameter flow cytometry or molecular techniques should be also used for risk stratification in AML at the time of HSCT. Despite the well-defined association of MRD and outcomes of HSCT in acute leukemias, there are still many open issues such as the role of additional pre-transplant consolidation for MRD eradication, the ability of HSCT to overcome negative influence of MRD positivity on survival, the impact of conditioning regimen intensity on MRD clearance post HSCT, and transplantation outcomes or the selection of optimal donor with regards to MRD status. In addition, the role of MRD assessment in guiding post-transplant maintenance treatment should also be addressed in prospective trials. These open issues mostly awaiting further clinical studies will be discussed in our current review.

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Section: The Role Of Mrd In Hsct For Amlmentioning

confidence: 99%

The Role of Measurable Residual Disease (MRD) in Hematopoietic Stem Cell Transplantation for Hematological Malignancies Focusing on Acute Leukemia

Czyż

Nagler

2019

IJMS

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“…The stratification of patients for these consolidation treatment options relies on the genetic risk assessed by cytogenetics and molecular analyses at initial diagnosis, the response to induction treatment, and the morbidity and mortality associated with the treatment options [1,2]. The concept of minimal or measurable residual disease (MRD) after induction has a significant impact on the type of consolidation and, increasingly, maintenance treatment [3]. MRD is defined as the detection of malignant cells at a submicroscopic level, and it has been shown to be an independent prognostic factor for the risk of relapse and death [4].…”

Section: Introductionmentioning

confidence: 99%

“…Multiparameter flow cytometry as well as molecular methods are routinely used for diagnosis and screening for residual disease in AML patients. While recurrent mutations in genes such as FLT3 or NPM1 have been incorporated in risk assessment for a long time [1,3], the introduction of next-generation sequencing (NGS) into the hematologic routine has enabled the discovery of a multitude of additional and often novel mutations [5]. The detection of druggable mutations has also opened the door for customized treatment strategies, some of which were integrated in the European LeukemiaNet (ELN) risk assessment and treatment for patients with AML [1,6,7].…”

Section: Introductionmentioning

confidence: 99%

Clonal Hematopoiesis after Autologous Stem Cell Transplantation Does Not Confer Adverse Prognosis in Patients with AML

Heini

Porret

Zenhaeusern³

et al. 2021

Cancers

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Introduction: Despite a 50% cure rate, relapse remains the main cause of death in patients with acute myeloid leukemia (AML) consolidated with autologous stem cell transplantation (ASCT) in first remission (CR1). Clonal hematopoiesis of indeterminate potential (CH) increases the risk for hematological and cardiovascular disorders and death. The impact of CH persisting after ASCT in AML patients is unclear. Materials and Methods: We retrospectively investigated the prognostic value of persisting DNMT3A, TET2, or ASXL1 (DTA) mutations after ASCT. Patients underwent stratification depending on the presence of DTA mutations. Results: We investigated 110 consecutive AML patients receiving ASCT in CR1 after two induction cycles at our center between 2007 and 2020. CH-related mutations were present in 31 patients (28.2%) after ASCT. The baseline characteristics were similar between patients with or without persisting DTA mutations after ASCT. The median progression free survival was 26.9 months in patients without DTA mutations and 16.7 months in patients with DTA mutations (HR 0.75 (0.42–1.33), p = 0.287), and the median overall survival was 80.9 and 54.4 months (HR 0.79 (0.41–1.51), p = 0.440), respectively. Conclusion: We suggest that DTA-CH after ASCT is not associated with an increased risk of relapse or death. The persistence of DTA mutations after induction should not prevent AML patients in CR1 from ASCT consolidation. Independent studies should confirm these data.

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“…Various studies have demonstrated that autologous HCT performed in CR1 has a low non-relapse mortality (NRM) and is associated with a lower relapse rate than consolidation chemotherapy alone [ 3 – 7 ]. Durable responses following autologous HCT have been reported within distinct AML subtypes including core binding factor or NPM1 -mutated AML [ 8 , 9 ]. Allogeneic HCT is the preferred option in patients with adverse risk profiles, as the graft-versus-leukemia (GvL) effect [ 10 , 11 ] cannot be provided by HDCT/autologous HCT outweighing in these patients the risks of graft-versus-host disease (GvHD).…”

Section: Introductionmentioning

confidence: 99%

Feasibility and efficacy of salvage allogeneic stem cell transplantation in AML patients relapsing after autologous stem cell transplantation

Shumilov

Shakhanova

Flach

et al. 2021

Bone Marrow Transplant

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Autologous hematopoietic cell transplantation (HCT) is suitable for consolidation of favorable-/intermediate-risk AML patients in CR1. However, ~50% of AML patients relapse after autologous HCT, and efficacy of subsequent salvage strategies including allogeneic HCT remains unclear. We studied 123 consecutive patients with newly diagnosed AML undergoing high-dose chemotherapy (HDCT)/autologous HCT in CR1. In relapsing patients afterwards, we analyzed salvage treatments and outcomes focusing particularly on salvage allogeneic HCT. Of 123 patients, 64 (52%) relapsed after autologous HCT. Subsequently, 13 (21%) received palliative therapy, whereas 51 (79%) proceeded to salvage therapy with a curative intent. Of the 47 patients with a curative intent and who did not proceed directly to allogeneic HCT, 23 (49%) achieved CR2 or had ongoing hematologic CR1 despite molecular relapse. Finally, 30 patients (47%) received allogeneic HCT with estimated 3-year leukemia-free and overall survival rates of 33% and 43%. Hematologic remission at allogeneic HCT and lack of acute GvHD had a positive impact on OS and LFS (p < 0.05). Our study suggests that almost 80% of AML patients can undergo salvage therapy following relapse after front-line HDCT/autologous HCT. Allogeneic HCT can provide cure in one third of patients relapsing after front-line HDCT/autologous HCT.

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Molecular minimal residual disease negativity and decreased stem cell mobilization potential predict excellent outcome after autologous transplant in NPM1 mutant acute myeloid leukemia

Abstract: Molecular minimal residual disease negativity and decreased stem cell mobilization potential predict excellent outcome after autologous transplant in NPM1 mutant acute myeloid leukemia.

Cited by 8 publications

References 15 publications

The Role of Measurable Residual Disease (MRD) in Hematopoietic Stem Cell Transplantation for Hematological Malignancies Focusing on Acute Leukemia

The Role of Measurable Residual Disease (MRD) in Hematopoietic Stem Cell Transplantation for Hematological Malignancies Focusing on Acute Leukemia

Clonal Hematopoiesis after Autologous Stem Cell Transplantation Does Not Confer Adverse Prognosis in Patients with AML

Feasibility and efficacy of salvage allogeneic stem cell transplantation in AML patients relapsing after autologous stem cell transplantation

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