&lt;p&gt;Acute myeloid leukemia patient with &lt;em&gt;FLT3-ITD&lt;/em&gt; and &lt;em&gt;NPM1&lt;/em&gt; double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis &lt;/p&gt;

Huang, Yan; Hu, Juan; Lu, Ting; Luo, Yi; Shi, Jimin; Wu, Wenjun; Han, Xiaoyan; Zheng, Weiyan; He, Jingsong; Zhang, Cai; Wei, Guoqing; Huang, He; Sun, Jie

doi:10.2147/cmar.s194523

Cited by 17 publications

(16 citation statements)

References 43 publications

(54 reference statements)

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“…Loghavi and colleagues reported that AML FLT3 -ITD +/NPM1+ patients with a DNMT3A mutation had shorter event-free survival compared to those in other mutation groups [ 61 ]. Similarly, recent studies have suggested that AML patients with concomitant DNMT3A R882+ /FLT3 -ITD +/NPM1+ mutations had a very poor prognosis, and allo-HSCT could moderately improve their survival [ 62 , 63 ]. Our study cohort included 21 AML FLT3 -ITD +/NPM1+ patients, 4 of whom had a DNMT3A R882 mutation.…”

Section: Discussionmentioning

confidence: 99%

Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms

Rosenthal

Герасимова

et al. 2021

PLoS ONE

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Identification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. Various NGS based in-house developed and commercial myeloid neoplasm panels have been integrated into routine clinical practice. However, some genes frequently mutated in myeloid malignancies are particularly difficult to sequence with NGS panels (e.g., CEBPA, CARL, and FLT3). We report development and validation of a 48-gene NGS panel that includes genes that are technically challenging for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies ≥5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n = 2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9–99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n = 2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms even in technically challenging genes.

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Section: Discussionmentioning

confidence: 99%

Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms

Rosenthal

Герасимова

et al. 2021

PLoS ONE

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“…However, some studies indicated that allogeneic SCT improves the prognosis in NPM1mutated AML with FLT3/ITD low AR 24,25 . Recently, Huang et al 26 found that SCT have better survival in adult AML patients with both NPM1 and FLT3/ITD mutations comparing to chemotherapy alone.…”

Section: Discussionmentioning

confidence: 99%

Nucleophosmin mutations confer an independent favorable prognostic impact in 869 pediatric patients with acute myeloid leukemia

Fang

Liu

et al. 2020

Blood Cancer J.

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Studies on the clinical significance of Nucleophosmin (NPM1) mutations in pediatric AML in a large cohort are lacking. Moreover, the prognosis of patients with co-occurring NPM1 and FLT3/ITD mutations is controversial. Here, we analyzed the impact of NPM1 mutations on prognoses of 869 pediatric AML patients from the TAGET dataset. The frequency of NPM1 mutations was 7.6%. NPM1 mutations were significantly associated with older age (P < 0.001), normal cytogenetics (P < 0.001), FLT3/ITD mutations (P < 0.001), and high complete remission induction rates (P < 0.05). Overall, NPM1-mutated patients had a significantly better 5-year EFS (P = 0.001) and OS (P = 0.016) compared to NPM1 wild-type patients, and this favorable impact was maintained even in the presence of FLT3/ITD mutations. Stem cell transplantation had no significant effect on the survival of patients with both NPM1 and FLT3/ITD mutations. Multivariate analysis revealed that NPM1 mutations were independent predictors of better outcome in terms of EFS (P = 0.004) and OS (P = 0.012). Our findings showed that NPM1 mutations confer an independent favorable prognostic impact in pediatric AML despite of FLT3/ITD mutations. In addition, pediatric AML patients with both NPM1 and FLT3/ITD mutations appear to have favorable prognoses and may not need hematopoietic stem cell transplantations.

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“…In CEBPA bi+ AML patients with sustained positive MRD after two consolidation cycles, the loss of negative MRD status at any time was the only independent risk factor for CIR, leukemia-free survival (LFS) and OS, while allo-HSCT achieved superior 3-year CIR (0% vs. 52.8%, p = 0.006) and LFS (88.9% vs. 47.2%, p = 0.027) rates compared to chemotherapy in MRD + patients in single center studies [ 20 , 21 ]. Among AML patients with nucleophosmin 1 (NPM1) mutation in single center study, those with MRD detected by both multiparameter flow cytometry (FCM) and real-time quantitative polymerase chain reaction (qRT-PCR) were classified as a subgroup with a high relapse risk (46–83%) following chemotherapy [ 22 ]; allo-HSCT reduced the CIR and improved DFS in NPM1 + AML in CR1 patients, especially those positive for FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) [ 23 ]. Therefore, MRD-directed risk stratification and the identification of additional risk factors would help guide transplant decisions for patients with fav-AML in CR1 (Table 1 ).…”

Section: Indications and Timing Of Allo-hsctmentioning

confidence: 99%

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

et al. 2021

Self Cite

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The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.

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<p>Acute myeloid leukemia patient with <em>FLT3-ITD</em> and <em>NPM1</em> double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis </p>

Cited by 17 publications

References 43 publications

Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms

Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms

Nucleophosmin mutations confer an independent favorable prognostic impact in 869 pediatric patients with acute myeloid leukemia

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

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