Mutational profiling of isolated myeloid sarcomas and utility of serum 2HG as biomarker of IDH1/2 mutations

Willekens, Christophe; Renneville, Aline; Broutin, Sophie; Saada, Véronique; Micol, Jean-Baptiste; Delahousse, J; Poinsignon, Vianney; Bories, Claire; Berthon, Céline; Itzykson, Raphaël; Boissel, Nicolas; Quivoron, Cyril; Terroir-Cassou-Mounat, Marie; Bosq, Jacques; Preudhomme, Claude; Paci, Angélo; Penard-Lacronique, Virginie; Botton, Stéphane de

doi:10.1038/s41375-018-0056-6

Cited by 18 publications

(7 citation statements)

References 15 publications

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“…Seventeen patients had gene sequencing, 76% had pathogenic mutations; 88% had at least one mutation and 23.5% had 2-3 mutations. RTK mutations was higher (56–85%), than reported before (55%) and NRAS is the most common (17.5%), details in table- 2 [ [22] , [23] , [24] , [25] , [26] ].…”

Section: Discussionmentioning

confidence: 94%

Extramedullary acute myeloid leukemia (eAML): Retrospective single center cohort study on clinico-pathological, molecular analysis and survival outcomes

Halahleh

Alhalaseh

Al-Rimawi

et al. 2021

Annals of Medicine and Surgery

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Introduction extramedullary acute myeloid leukemia (eAML) is characterized by extramedullary tumor formation infiltrated by myeloid blasts, with or without maturation and effaced architecture. The clinical, genetic and molecular aspects and overall outcomes are well defined worldwide, but not well characterized in our region. Purpose and methods This is a retrospective single center cohort study on 32 patients, who were identified over 10 years to study the clinical, pathologic and genetic-molecular aspects, and survival outcomes. Results eAML is rare (1%), occurs at a younger age with male predominance. Central nervous system (CNS) with facial bone invasion is most commonly identified (34.4%). 45.5% were positive for conventional myeloid markers (MPO), CD33, CD117, and 36% positive for CD34 and CD68. 54% with normal karyotype had deleterious mutations on further testing. NGS revealed pathogenic mutations in 76%(N-9/17) and none tested positive for P53, IDH1 or IDH2. At a median follow up time of 43mo (range, 8.6–80mo); 37.5%(N-12) were in complete remission, 62.5%(N-20) relapsed. 28% of relapses were after allotransplant. 31%(N-10) alive and continued in complete remission(CR), and 69%(N-22) of patients have died. Median overall survival (OS) is 18.4 and relapse free survival (RFS) 18.7 months. OS and RFS were significantly better in patients, who attained CR after induction (IC 11.9 mo vs zero; P = 0.0001; IC 12mo vs zero; P = 0.0001) compared to patients with relapsed disease; and in patients who received allo-transplant consolidation with median OS and RFS 42 vs 8.5mo (P = 0.002) and 42months vs 10 mo (P = 0.006). Thus allotransplant may be considered for all eligible patients in first CR. Conclusion achievement of complete remission after induction therapy is associated with improved outcomes in eAML. Allotransplant in first complete remission may be the most effective modality for achieving long-term remissions.

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Section: Discussionmentioning

confidence: 94%

Extramedullary acute myeloid leukemia (eAML): Retrospective single center cohort study on clinico-pathological, molecular analysis and survival outcomes

Halahleh

Alhalaseh

Al-Rimawi

et al. 2021

Annals of Medicine and Surgery

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“…There are very few reports of IDH mutations in patients with EM‐AML. In a small case series on isolated MS, six (42%) of 14 patients had an IDH mutation (including four IDH2 and two IDH1 ) 36 . A recent case study reported an IDH2 mutation on NGS of paired EM and marrow samples in one of seven patients with MS 37 .…”

Section: Discussionmentioning

confidence: 99%

“…In a small case series on isolated MS, six (42%) of 14 patients had an IDH mutation (including four IDH2 and two IDH1). 36 A recent case study reported an IDH2 mutation on NGS of paired EM and marrow samples in one of seven patients with MS. 37 In our cohort, five (26%) patients had IDH1 mutation and two (11%) harbored IDH2 mutation on EM-tissue NGS. The IDH1 mutation was significantly more prevalent on EM-site NGS than non-EM samples.…”

Section: Discussionmentioning

confidence: 99%

Molecular annotation of extramedullary acute myeloid leukemia identifies high prevalence of targetable mutations

Ball

Knepper

Deutsch

et al. 2022

Cancer

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BACKGROUND: Genomic landscape of extramedullary acute myeloid leukemia (EM-AML), including myeloid sarcoma (MS) and leukemia cutis (LC), is not well characterized. The potential utility of next-generation sequencing (NGS) using EM tissue is not established. METHODS:In this multicenter retrospective study, clinical and NGS data were collected on patients with EM-AML. All statistical analyses were performed in SPSS Statistics (v 26). RESULTS: Our study included 58 patients with EM-AML. The median age at diagnosis was 62 years; 59% of patients had MS and 33% had LC. EM-AML was isolated (i.e., without blood or marrow involvement) in 31% and was first noted at relapse in 60% of patients. Median overall survival in our cohort was 18.2 months overall, with 19.1 months and 11.6 months in the newly diagnosed and the relapsed/refractory patients, respectively. At least one targetable or potentially targetable alteration was present in 52% of patients with EM-site NGS, with 26% IDH1, 21% NPM1, 11% IDH2, 6% FLT3, and 13% KMT2A-PTD. Mutations in IDH1 were significantly more prevalent on NGS from EM tissue than non-EM (blood or marrow) samples (26% vs. 3%; p = .030). Three of four patients treated with IDH inhibitors based on EM-site NGS experienced a complete response. CONCLUSIONS: Targetable mutations are frequent in EM-AML and EM-site NGS is warranted for selecting potential targeted therapies for patients with EM-AML..

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“…The PET/CT potential utility in monitoring and assessing therapeutic response in MS has been emphasized by Lee et al (35). Although we have gained further insight into the cytogenetic and molecular abnormalities of MS, such as chromosomal abnormalities like inv (16) and t (8,21), and mutations in NPM1 and FLT3, the prognostic impact of genetic features remains poorly understood due to the small sample size (16,36,37). Therefore, another limitation is that it lacks information on the patients' imaging, cytogenetic, and molecular features.…”

Section: Limitationsmentioning

confidence: 99%

Incidence, clinical characteristics, and prognostic nomograms for patients with myeloid sarcoma: A SEER-based study

Xing

Zhu

et al. 2022

Front. Oncol.

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BackgroundMyeloid sarcoma (MS) is a rare hematological tumor that presents with extramedullary tumor masses comprising myeloid blasts. A controversial issue is whether MS involving normal hematopoietic sites (liver, spleen, and lymph nodes) should be excluded in future studies. We aimed to compare MS characteristics and outcomes involving hematopoietic and non-hematopoietic sites and construct a prognostic nomogram exclusively for the latter.MethodsData from patients diagnosed with MS between 2000 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. According to the primary site, patients were classified as having MS involving hematopoietic sites (hMS) or non-hematopoietic sites (eMS). Clinical characteristics and survival outcomes were compared between the two groups using Wilcoxon, chi-square, and log-rank tests. Cox regression analysis was used to identify eMS prognostic factors to establish prognostic nomograms. The models’ efficiency and value were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultsIn total, 694 patients were enrolled, including 86 with hMS and 608 with eMS. There were no sex, race or marital status distribution differences between the two groups. Patients with eMS had better overall and cancer-specific survival rates than those with hMS. Additionally, prognostic factor effects differed between the two groups. Patients with eMS were randomly divided into the training (number of patiens, n=425) and validation cohorts (n=183). Age, first primary tumor, primary site, and chemotherapy were used to establish nomograms. The C-index values of overall survival (OS) and cancer-specific survival (CSS) nomograms were 0.733 (validation: 0.728) and 0.722 (validation: 0.717), respectively. Moreover, ROC, calibration curves, and DCA confirmed our models’ good discrimination and calibration ability and potential clinical utility value.ConclusionOur study described the differences between patients with eMS and those with hMS. Moreover, we developed novel nomograms based on clinical and therapeutic factors to predict patients with eMS’ 1-, 3- and 5-year survival rates.

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Mutational profiling of isolated myeloid sarcomas and utility of serum 2HG as biomarker of IDH1/2 mutations

Cited by 18 publications

References 15 publications

Extramedullary acute myeloid leukemia (eAML): Retrospective single center cohort study on clinico-pathological, molecular analysis and survival outcomes

Extramedullary acute myeloid leukemia (eAML): Retrospective single center cohort study on clinico-pathological, molecular analysis and survival outcomes

Molecular annotation of extramedullary acute myeloid leukemia identifies high prevalence of targetable mutations

Incidence, clinical characteristics, and prognostic nomograms for patients with myeloid sarcoma: A SEER-based study

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