Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing

Ahn, Jae‐Sook; Kim, TaeHyung; Jung, Sung-Hoon; Ahn, Seo-Yeon; Jung, Seung-Yeon; Song, Ga‐Young; Kim, Mi-Hee; Yang, Deok‐Hwan; Lee, Je‐Jung; Choi, Seung-Hyun; Lee, Jayeon; Park, Seong-Kyu; Moon, Joon Ho; Lee, Hui Young; Kim, Kyoung Ha; Cai, Yu; Yi, Seong Yoon; Novitzky‐Basso, Igor; Zhang, Zhaolei; Kim, Hyeoung-Joon; Kim, Dennis Dong Hwan

doi:10.1038/s41409-020-01165-x

Cited by 10 publications

(10 citation statements)

References 34 publications

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“…This negative impact on relapse-free survival (RFS) is explained by exon 17 mutations (including D816V ) alone, and the role of the exon 8/10/11 mutation remains elusive. Similar concerns apply to the case of a double CEBPA mutation, which is not considered a favorable prognostic factor in the presence of chromatin, cohesion, or splicing factor mutations 6 . In addition, this opinion should be updated because it has recently been shown that CEBPA with in-frame mutations in the bZip domain, rather than double mutations, confers a favorable impact on outcomes.…”

Section: Allo-sct For Aml In Cr1 In the Era Of Genomicsmentioning

confidence: 98%

“…Ahn et al . explored the role of MRD in AML CR1 patients with normal karyotype ( n =124), which would significantly overlap with the ELN intermediate prognosis group 6 . They showed that allo-SCT recipients had significantly longer overall survival (OS) compared with those who received chemotherapy alone in the MRD pos group, while the outcome was almost the same for the MRD neg group, irrespective of allo-SCT.…”

Section: Allo-sct For Aml In Cr1 In the Era Of Genomicsmentioning

confidence: 99%

“…In this regard, the assessment of MRD markers and refinement of basic disease risk evaluation using genomic profiling may help identify a subset of this class that does not require upfront allo-SCT. Ahn et al explored the role of MRD in AML CR1 patients with normal karyotype (n=124), which would significantly overlap with the ELN intermediate prognosis group 6 . They showed that allo-SCT recipients had significantly longer overall survival (OS) compared with those who received chemotherapy alone in the MRD pos group, while the outcome was almost the same for the MRD neg group, irrespective of allo-SCT.…”

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confidence: 99%

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Advances in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia

2022

BCT

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In acute leukemia, advances have been made in therapeutic strategies centered on allogeneic hematopoietic stem cell transplantation (allo-SCT), three of which are presented here. The indication of allo-SCT for acute myeloid leukemia (AML) in 1 st complete remission (CR1) has been debated. Genomic medicine has helped us gain a deeper understanding of this disease, some of which may serve as prognostic factors. Such genetic abnormalities could also help measure minimal residual disease (MRD) and provide additional clues to estimate the efficacy of chemotherapy. Combined with existing prognostic factors, these data can be used to construct a more accurate prognostic model, providing an optimal indication of allo-SCT for AML in CR1. Furthermore, overall treatment algorithms for high-risk AML after allo-SCT should include prophylactic and pre-emptive treatment to prevent relapse. These include immunotherapy using donor lymphocyte infusion (DLI), FLT3 inhibitors in FLT3-mutated AML, hypomethylating agents, or a combination of DLI with these agents. Clinical trials are currently ongoing to elucidate the role of these strategies, which will lead to a risk-adapted treatment for preventing relapse in high-risk AML. CD19-targeted chimeric antigen receptor (CAR) T-cell therapy induces a remarkable response in B-acute lymphoid leukemia (B-ALL); however, relapse remains a major problem. In this regard, allo-SCT as a consolidation treatment after CAR-T cell therapy for B-ALL is recommended for pediatric and adult patients. Achieving complete remission (CR) with CAR-T cell therapy is considered a promising bridging therapy to allo-SCT. Novel CAR-T treatment techniques are being developed to change their role as a pretransplant treatment.

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Section: Allo-sct For Aml In Cr1 In the Era Of Genomicsmentioning

confidence: 98%

Section: Allo-sct For Aml In Cr1 In the Era Of Genomicsmentioning

confidence: 99%

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confidence: 99%

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Advances in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia

2022

BCT

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“…The survival analysis was performed following the protocol outlined in a previous study [33]. Consequently, Mantel-Byar tests were used to compare the survival data, the Simon and Makuch method was used for graphical representation, and time-dependent multivariate Cox proportional hazard models were used to examine time-dependent covariates by considering allogeneic HCT as a time-dependent covariate [34].…”

Section: Statistical Analysesmentioning

confidence: 99%

Next‐generation sequencing‐based analysis to assess the pattern of relapse in patients with Philadelphia‐positive acute lymphoblastic leukemia

Ahn

Kim

Jung

et al. 2022

eJHaem

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In this study, we performed serial monitoring using targeted DNA sequencing to identify genetic alterations in adults with Philadelphia-positive acute lymphoblastic leukemia (Ph-ALL). Deep sequencing was performed by targeting the coding regions of 45 genes with recurrent driver mutations and 1129 single nucleotide polymorphism sites. Of the 43 patients that we examined, at least one case of genetic alterations was detected in 38 (88%) of the 43 patients at diagnosis (somatic mutations in 10 patients [23%] and copy number aberrations [CNA] in 36 patients [84%]). The most frequently detected CNA lesions were in IKZF1 (n = 25, 58%) and the most frequently mutated gene was SETD2 (n = 5). At least one genetic abnormality (loss, gain, or persistence) was observed in all the samples obtained at relapse that were available for analysis (n = 15), compared with the samples obtained at diagnosis (disappearance of any previously detected genetic alterations: 11 patients [73%]; new genetic abnormalities: nine patients [60%]; and persistent genetic abnormalities: eight patients [53%]].The most frequently deleted lesions were in IKZF1 (n = 9, 60%), and the most frequently mutated gene was ABL1 (eight patients, 53%). Our data indicate that leukemic Jae-Sook Ahn, TaeHyung Kim and Sung-Hoon Jung contributed equally to this work.

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“…In recent years, NGS assay has been used in monitoring minimal (measurable) residual disease (MRD). Using unique molecular identification (UMI) barcode, NGS sequencing error and noise background have been reduced, which makes NGS assay a good tool in monitoring MRD [9][10][11][12][13][14][15][16] . NGS assay has also been used in single cell sequencing, which is a powerful tool for revealing information about clonal evolution 17,18 .…”

Section: Ngsmentioning

confidence: 99%

Molecular testing for acute myeloid leukemia

Qin¹

2021

Cancer Biol. Med.

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In the era of personalized medicine, information on molecular change at the gene level is important for patient care. Such information has been used for disease classification, diagnosis, prognosis, risk stratification, and treatment, which is especially important in cancer patient care. Many molecular tests exist and can be used to detect the molecular changes at gene level. These tests include, but are not limited to, karyotyping, endpoint polymerase chain reaction (PCR), real-time PCR, Sanger sequencing, pyrosequencing, nextgeneration sequencing, and so forth. How to use the right tests for the right patients at the right time is essential for optimal patient outcome. This review puts together some information on molecular testing for acute myeloid leukemia.

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Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing

Cited by 10 publications

References 34 publications

Advances in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia

Advances in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia

Next‐generation sequencing‐based analysis to assess the pattern of relapse in patients with Philadelphia‐positive acute lymphoblastic leukemia

Molecular testing for acute myeloid leukemia

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