Tumor Molecular Profiling: Pediatric Results of the ProfiLER Study

2020 ◽  
pp. 785-795
Author(s):  
Sarah Benezech ◽  
Pierre Saintigny ◽  
Valery Attignon ◽  
Daniel Pissaloux ◽  
Sandrine Paindavoine ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Genomic Alteration ◽  
Comparative Genomic ◽  
Tumor Subtypes ◽  
Patients With Cancer ◽  
Targeted Agent ◽  
Tumor Genome ◽  
Immunologic Profile ◽  
Recommended Therapy ◽  
Generation Sequencing

PURPOSE The Program to Establish the Genetic and Immunologic Profile of Patient's Tumor for All Types of Advanced Cancer study (ClinicalTrials.gov identifier: NCT01774409 ) analyzed the genome of refractory cancers to identify a potential molecular-based recommended therapy (MBRT). The objectives of the pediatric substudy were to describe the incidence of genomic mutations, the MBRT, and the treatments undertaken with a molecular-targeted agent in a pediatric cohort. METHODS The tumor genome was analyzed within a 69-gene next-generation sequencing panel and an array comparative genomic hybridization assay. The results were evaluated by a multidisciplinary molecular board, and the targeted therapies were provided in the setting of a clinical trial or through compassionate use programs, when indicated. RESULTS Between November 2013 and June 2017, 50 patients younger than 19 years who were treated for a high-risk or relapsing tumor were included. Sarcomas (n = 24; 47%), CNS tumors (n = 14; 29%), and neuroblastomas (n = 5; 10%) were the most frequent tumor subtypes. Seven patients (14%) were excluded because no DNA could be recovered. Among the 43 remaining patients, 10 exhibited at least one targetable genomic alteration. Ultimately, four patients (8%) were treated with the recommended targeted therapy. CONCLUSION The results of this study confirm treatment with a targeted therapy for pediatric patients with cancer is still limited at present, as also is reported for adults.

scholarly journals P14.127 From next generation sequencing and comparative genomic hybridization to personalised medicine for adult primary brain tumors: the profiler trial

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii99-iii99
Author(s):  
A Bonneville-levard ◽  
D Frappaz ◽  
D Pissaloux ◽  
Q Wang ◽  
D Perol ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Next Generation Sequencing ◽  
Brain Tumors ◽  
Comparative Genomic Hybridization ◽  
Comparative Genomic ◽  
Next Generation ◽  
Genomic Hybridization ◽  
Primary Brain Tumors ◽  
Generation Sequencing

Abstract BACKGROUND Personalized anti-tumoral therapies may currently be proposed on the basis of immuno-histochemistry, but also next-generation sequencing and comparative genomic hybridization. ProfiLER trial explored the feasibility, efficacy and the impact of molecular profiling for patients with solid or hematological advanced cancers including brain tumors. MATERIAL AND METHODS Patients with primary brain tumors, pre-treated with at least one line of anti-cancer treatment, could be included in this multicentric prospective trial. A molecular profile (next-generation sequencing and comparative genomic hydridization) was established on fresh or archived sample. Weekly molecular tumor board analysed results to propose as far as possible a molecular targeted therapy. RESULTS between February 2013 and December 2015, 141 patients with primary brain tumor were enrolled. One hundred five samples were further analyzed as 30 samples were excluded, and 6 are on-going. The rate of screen failure was 16/33 for stereotactic biopsy (49%) versus 11/104 (11%) for removal. The main representative histologic type of tumors were glioblastoma (n=46, 43,8%), low grade glioma (n=26, 24,8%), high grade glioma (n=12, 11,4%) and atypical and anaplastic meningioma (n=8, 7,6%). Median delay between the diagnostic of the primitive tumor and the inclusion in ProfiLER study was 2.7 years (0.2 - 29 years). Median delay between the consent and the results of the multidisciplinary meeting was 2.8 months (1–7.1 months). Forty-three patients (41%) presented at least one “druggable molecular alteration”. The most frequently altered genes were CDKN2A (n=18, 29%), EGFR (n=12, 20%), PDGFRa (n=8, 13%), PTEN (n=8, 13%), CDK4 (n=7, 11%), KIT (n=6, 10%), PIK3CA (n=5, 8%), MDM2 (n=3, 5%). Sixteen patients could not have a proposition of specific treatment due to death before MBT (n=5, 31.3%), lack of available clinical trials (n=9, 56%), or ambiguous results (n=2, 12.5%). Among the 27 patients (26%) for whom a specific therapy has been proposed, only six patients ultimately received a medical targeted therapy (everolimus n=3, erlotinib n=1, ruloxitinib n=1, sorafenib n=1). Four patients discontinued the treatment for toxicity, the 2 others for clinical progression. CONCLUSION routine high-throughput sequencing is feasible for brain tumors but delays should be reduced to be able to propose targeted therapies to patients fit enough to benefit from experimental treatment. Macroscopic surgery is the best way to obtain workable samples. Specific panel genes for neurologic tumors should be developed, as well as change of practices concerning exclusion criteria in clinical trials.

Targeted agent use in patients with cancer at the end of life.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 215-215 ◽  
Author(s):  
David Hui ◽  
Meghan Sri Karuturi ◽  
Kimberson Cochien Tanco ◽  
Jung Hye Kwon ◽  
Sun Hyun Kim ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
End Of Life ◽  
Hematologic Malignancies ◽  
Poor Quality ◽  
Chemotherapeutic Agents ◽  
Concurrent Chemotherapy ◽  
Targeted Agents ◽  
Patients With Cancer ◽  
Lung Malignancies ◽  
Targeted Agent

215 Background: Chemotherapy use at the end of life is considered an indicator of poor quality of care. The use of targeted agent has not been well characterized. In this study, we determined the frequency and predictors of targeted therapy use in the last 30 days of life. Methods: All adult patients residing in the Houston area who died of advanced cancer between September 1, 2009 and February 28, 2010 and had contact with our institution within the last three months of life were included. We collected baseline demographics and data on chemotherapy and targeted agents. Results: 816 patients were included: average age 62 (range 21 to 97), female 48% and White 61%. The median interval between the last treatment and death was 47 (interquartile range 21 to 97) days for targeted agents and 57 (26 to 118) days for chemotherapeutic agents. 116 (14%) patients received targeted agents and 147 (18%) received chemotherapy within the last 30 days of life. 43 (5%) patients received targeted agents had concurrent chemotherapy. The most common targeted agents in the last 30 days of life were erlotinib (n=25), bevacizumab (n=20) and rituximab (n=11). In multivariate analysis, younger age, hematologic, and lung malignancies were associated with increased targeted agent use in the last 30 days of life (Table). Conclusions: Targeted agents were used as often as chemotherapy at the end of life, particularly among younger patients and those with hematologic malignancies. Guidelines on targeted therapy use at the end of life are needed. [Table: see text]

A multicenter effort to identify driver mutations and employ targeted therapy in patients with lung adenocarcinomas: The Lung Cancer Mutation Consortium (LCMC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8019-8019 ◽  
Author(s):  
Bruce E. Johnson ◽  
Mark G. Kris ◽  
Lynne D Berry ◽  
David J. Kwiatkowski ◽  
Anthony John Iafrate ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Median Survival ◽  
Driver Mutations ◽  
Genomic Alteration ◽  
Treatment Information ◽  
Met Amplification ◽  
Targeted Agent ◽  
Never Smokers ◽  
Lung Adenocarcinomas

8019 Background: The detection of driver mutations in the EGFR and ALK genes and targeted therapy has transformed treatment of lung cancer. The LCMC was established in 2009 to assay lung adenocarcinomas for driver genomic alterations in 10 genes and to study and treat patients by their molecular subtypes. Methods: The 14-member LCMC enrolled patients with metastatic adenocarcinoma of the lung and tested their tumors in CLIA laboratories for KRAS, EGFR, HER2, BRAF, PIK3CA, AKT1, MEK1, and NRAS mutations using multiplexed assays, and for ALK rearrangements and MET amplifications using fluorescence in situ hybridization (FISH). Results: 1,102 eligible patients were enrolled; 1,007 underwent testing for at least one genomic alteration with 733 undergoing testing for all 10 genes. 600 patients were women (60%) with a median age of 63; 341 were never smokers (34%) and 589 former smokers (58%). A driver alteration was detected in 622 (62%) of the 1,007 with any genotyping, and in 465 (63%) of the 733 fully genotyped cases. Among the tumors with full genotyping, drivers were found as follows: KRAS 182 (25%), sensitizing EGFR 107 (15%), ALK rearrangements 56 (8%), other EGFR 43 (6%), two genes 29 (4%), BRAF 16 (2%), HER2 15 (2%), PIK3CA 6 (1%), MET amplification 5 (1%), NRAS 5 (1%), MEK1 1 (<1%), and AKT1 0 (0%). Results were used to select targeted therapy or targeted trials in 279 patients with a driver alteration (28% of 1,007 total). Among 938 patients with clinical follow-up and treatment information, 264 with a driver alteration treated with a targeted agent had a median survival of 3.5 years; 313 with a driver who did not receive targeted therapy had a median survival of 2.4 years; while 361 without an identified driver had a median survival of 2.1 years (p<0.0001). Conclusions: An actionable driver alteration was detected in 62% of tumors from patients with lung adenocarcinomas, leading to use of a targeted therapy in 28%. The patients with an identified driver treated with a targeted agent lived longer than those patients who did not receive targeted therapy. Multiplexed genomic testing can aid physicians in matching patients with targeted treatments and appropriate clinical trials.

scholarly journals Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruofei Du ◽  
Xin Wang ◽  
Lixia Ma ◽  
Leon M. Larcher ◽  
Han Tang ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Patients ◽  
Adverse Reactions ◽  
Cox Regression ◽  
Target Therapy ◽  
Skin Damage ◽  
Data Set ◽  
Patients With Cancer ◽  
Number Of Patients ◽  
Significant Difference

Abstract Background The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data. Methods A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups. Results A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group. Conclusion The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.

The novel approach to distinguish primary multiple lung adenocarcinomas from intrapulmonary metastases by next generation sequencing in Chinese patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20506-e20506
Author(s):  
Lin Li ◽  
Naiquan Mao ◽  
Yingcheng Lyu ◽  
Huayue Lin ◽  
Kefeng Wang ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Chinese Patients ◽  
Comparative Genomic ◽  
Genomic Profiling ◽  
Next Generation ◽  
Architectural Patterns ◽  
Chinese Cohort ◽  
Lung Adenocarcinomas ◽  
Generation Sequencing

e20506 Background: Differentiation of multiple primary lung cancer (MPLC) from intrapulmonary metastasis (IPM) is critical to determine clinical stage. Although clinicopathological features could provide certain evidences, it’s still challenging to identify the tumor malignancy accurately. In General, standard histopathologic approach is adequate in most cases, but has notable limitations in the recognition of IPMs. Herein, we propose an integrated molecular algorithm to facilitate MPLCs and IPMs diagnosis in the clinical practice. Methods: 40 Chinese patients with lung adenocarcinomas were enrolled in the study, 84 tumor samples were collected for next-generation sequencing. Somatic alterations with variant allele fraction (VAF) ≥1% were taken into account for molecular algorithm. A genomic database of 2,471 Chinese lung adenocarcinomas (LUAD) was used to calculate odds of coincidental occurrence, prevalence of individual mutation prevalence. Tumor relatedness diagnosed by histopathologic assessment was contrasted with comparative genomic profiling by subsequent NGS. Moreover, the performance of molecular algorithm prediction was evaluated as well. Results: Firstly, we compared the performance of comprehensive next-generation sequencing (NGS) with standard histopathologic approaches for distinguishing NSCLC subtypes in clinical practice. The genomic profiling was described as following: EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P<0.05). Further analysis showed that TP53 alterations occurred less frequently in MPLCs compared to large Chinese cohort (22.9% vs 51.0%, P<0.05). TP53 alterations occurred less frequently in MPLCs compared to large Chinese cohort (P<0.05). The classifications based on the three different methodologies mentioned above were compared. Molecular algorithm prediction was concordant with NGS in 21 cases (52.5%), particularly in the prediction of MPLC. Retrospective review highlighted several histologic challenges, including morphologic progression in some IPMs. For the five undetermined cases, two showed differences in architectural patterns, and remained cases have nodules presented as adenocarcinoma in situ, or minimally invasive adenocarcinoma. Of 28 MPLC cases defined by NGS, 25 cases had unique somatic mutations per pair Based on calculation from the prevalence of EGFR L858R mutation (27%) in large Chinese cohort, the odds of coincidental occurrence of the mutation in two unrelated tumors was 7.3%. Taking together, EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P<0.05). Molecular algorithm prediction was concordant with NGS in 21 cases (52.5%). Conclusions: Our results support broad panel NGS to assist differential diagnosis to assist approach in clinical practice. It is necessary to conduct large clinical study to establish comprehensive algorithm models to assist diagnosis and predict clinical outcome.

scholarly journals Next Generation Sequencing Detects Premeiotic Errors in Human Oocytes

2022 ◽  
Vol 23 (2) ◽  
pp. 665
Author(s):  
Harita Ghevaria ◽  
Sioban SenGupta ◽  
Roy Naja ◽  
Rabi Odia ◽  
Holly Exeter ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Polar Body ◽  
Independent Study ◽  
Comparative Genomic ◽  
Next Generation ◽  
Consistent Finding ◽  
Autosomal Aneuploidy ◽  
First Polar Body ◽  
Germinal Mosaicism ◽  
Generation Sequencing

Autosomal aneuploidy is the leading cause of embryonic and foetal death in humans. This arises mainly from errors in meiosis I or II of oogenesis. A largely ignored source of error stems from germinal mosaicism, which leads to premeiotic aneuploidy. Molecular cytogenetic studies employing metaphase fluorescence in situ hybridization and comparative genomic hybridisation suggest that premeiotic aneuploidy may affect 10–20% of oocytes overall. Such studies have been criticised on technical grounds. We report here an independent study carried out on unmanipulated oocytes that have been analysed using next generation sequencing (NGS). This study confirms that the incidence of premeiotic aneuploidy in an unselected series of oocytes exceeds 10%. A total of 140 oocytes donated by 42 women gave conclusive results; of these, 124 (88.5%) were euploid. Sixteen out of 140 (11.4%) provided evidence of premeiotic aneuploidy. Of the 140, 112 oocytes were immature (germinal vesicle or metaphase I), of which 10 were aneuploid (8.93%); the remaining 28 were intact metaphase II - first polar body complexes, and six of these were aneuploid (21.4%). Of the 16 aneuploid cells, half contained simple errors (one or two abnormal chromosomes) and half contained complex errors. We conclude that germinal mosaicism leading to premeiotic aneuploidy is a consistent finding affecting at least 10% of unselected oocytes from women undergoing egg collection for a variety of reasons. The importance of premeiotic aneuploidy lies in the fact that, for individual oocytes, it greatly increases the risk of an aneuploid mature oocyte irrespective of maternal age. As such, this may account for some cases of aneuploid conceptions in very young women.

scholarly journals Next generation sequencing demonstrates association between tumor suppressor gene aberrations and poor outcome in patients with cancer

Cell Cycle ◽  
2015 ◽  
Vol 14 (11) ◽  
pp. 1730-1737 ◽  
Author(s):  
Maria Schwaederle ◽  
Gregory A Daniels ◽  
David E Piccioni ◽  
Santosh Kesari ◽  
Paul T Fanta ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Next Generation ◽  
Patients With Cancer ◽  
Poor Outcome ◽  
Generation Sequencing

Off-label targeted therapy (TT) use in recurrent/metastatic NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18688-e18688
Author(s):  
Victoria Wang ◽  
Chenming Cui ◽  
Lei Yang ◽  
Gerald Li ◽  
Alexa Betzig Schrock ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Clinical Efficacy ◽  
Real World ◽  
Survival Advantage ◽  
Genomic Alteration ◽  
Genomic Profiling ◽  
Off Label ◽  
Number Of Patients ◽  
Tier System ◽  
Line Of Therapy

e18688 Background: Comprehensive genomic profiling (CGP) is an established diagnostic approach to select patients for TT. As CGP gains wide adoption, an increasing number of patients are found to harbor driver mutations for which no approved TT is available. This is often addressed through use of matched TKI and mAb approved for other mutations or anatomic sites. In this work, we examined the clinical efficacy of off-label TT in R/M NSCLC. Methods: Using a de-identified NSCLC clinico-genomic database (CGDB), we identified 6590 NSCLC patients who underwent Foundation Medicine CGP, of whom 17.8% harbored an actionable genomic alteration (GA) for which an FDA-approved TT was available and 2% (133) whose GA (MET ex-14, uncommon EGFRm, EGFR ex20ins, HER2 amp/mut, RET fusion, BRAF class 2/3) lacked an FDA-approved TT (62 in 1L and 71 in ≥2L ) who received matched off-label TT. ESMO Scale for Clinical Actionability (ESCAT) was used to grade levels of evidence. For patients who progressed on initial chemotherapy (range 2 – 9 lines, median 3), we calculated clinical efficacy using the ratio of real world PFS on targeted therapy (rw-PFS2) to rw-PFS on the last prior line of therapy (rw-PFS1) and used a cut-off of PFS2/PFS1 > 1.3 to determine off-label drug efficacy. Results: Of the 133 patients reviewed, 72 were classified as ESCAT level IB (uncommon EGFRm, MET-ex14), 45 IIB (HER2m/amp, EGFR ex-20ins), 7 IC (RET fusions). PFS varied significantly by mutation and line of therapy (table 1) with uncommon EGFRm+ and MET-ex14 exhibiting best response while EGFR ex20 ins, BRAF class 2/3 and HER2 amp fared significantly worse. 55.8% of the patients (39 of 71) reached a PFS2/PFS1 ratio > 1.3 (two-sided 95% CI, 45.3 % – 68.7 %), ranging from 93% in uncommon EGFRm+ down to 20% in HER2 amp and 44% in ex20ins. Conclusions: We provide real-world evidence to assess off-label TT in NSCLC. Clinical benefit derived from off-label TT is unevenly distributed across various mutations with most survival advantage accruing to specific mutations (MET-ex14 and uncommon EGFRm) at the expense of others (HER2 amp). Survival advantage was highly influenced by two factors: A) the timing of CGP with the earlier recipients of genomic profiling achieving better outcome, B) the identity of the driver mutation, highlighting the role of clinical actionability tier system to define level of evidence supporting such intervention.[Table: see text]

scholarly journals Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1588 ◽  
Author(s):  
Sabrina Weber ◽  
Benjamin Spiegl ◽  
Samantha O. Perakis ◽  
Christine M. Ulz ◽  
Peter M. Abuja ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Reference Materials ◽  
Test Performance ◽  
Liquid Biopsy ◽  
Attractive Alternative ◽  
Routine Practice ◽  
Patients With Cancer ◽  
Technical Evaluation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Molecular profiling from liquid biopsy, in particular cell-free DNA (cfDNA), represents an attractive alternative to tissue biopsies for the detection of actionable targets and tumor monitoring. In addition to PCR-based assays, Next Generation Sequencing (NGS)-based cfDNA assays are now commercially available and are being increasingly adopted in clinical practice. However, the validity of these products as well as the clinical utility of cfDNA in the management of patients with cancer has yet to be proven. Within framework of the Innovative Medicines Initiative (IMI) program CANCER-ID we evaluated the use of commercially available reference materials designed for ctDNA testing and cfDNA derived from Diagnostic Leukaphereses (DLA) for inter- and intra-assay as well as intra- and inter-laboratory comparisons. In three experimental setups, a broad range of assays including ddPCR, MassARRAY and various NGS-based assays were tested. We demonstrate that both reference materials with predetermined VAFs and DLA samples are extremely useful for the performance assessment of mutation analysis platforms. Moreover, our data indicate a substantial variability of NGS assays with respect to sensitivity and specificity highlighting the importance of extensive validation of the test performance before offering these tests in clinical routine practice.

scholarly journals A rare atypical chronic myeloid leukemia BCR-ABL1 negative with concomitant JAK2 V617F and SETBP1 mutations: a case report and literature review

2020 ◽  
Vol 11 ◽  
pp. 204062072092710
Author(s):  
Tianqi Gao ◽  
Changhui Yu ◽  
Si Xia ◽  
Ting Liang ◽  
Xuekui Gu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Targeted Therapy ◽  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Jak2 V617f ◽  
Next Generation ◽  
Bone Marrow Fibrosis ◽  
Atypical Chronic Myeloid Leukemia ◽  
Generation Sequencing ◽  
Marrow Fibrosis

Atypical chronic myeloid leukemia (aCML) BCR-ABL1 negative is a rare myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) for which no standard treatment currently exists. The advent of next-generation sequencing has allowed our understanding of the molecular pathogenesis of aCML to be expanded and has made it possible for clinicians to more accurately differentiate aCML from similar MDS/MPN overlap syndrome and MPN counterparts, as MPN-associated driver mutations in JAK2, CALR, or MPL are typically absent in aCML. A 55-year old male with main complaints of weight loss and fatigue for more than half a year and night sweats for more than 2 months was admitted to our hospital. Further examination revealed increased white blood cells, splenomegaly, and grade 1 bone marrow fibrosis with JAK2 V617F, which supported a preliminary diagnosis of pre-primary marrow fibrosis. However, in addition to JAK2 V617F (51.00%), next-generation sequencing also detected SETBP1 D868N (46.00%), ASXL1 G645fs (36.09%), and SRSF2 P95_R102del (33.56%) mutations. According to the 2016 World Health Organization diagnostic criteria, the patient was ultimately diagnosed with rare aCML with concomitant JAK2 V617F and SETBP1 mutations. The patient received targeted therapy of ruxolitinib for 5 months and subsequently an additional four courses of combined hypomethylating therapy. The patient exhibited an optimal response, with decreased spleen volume by approximately 35% after therapy and improved symptom scores after therapy. In diagnosing primary bone marrow fibrosis, attention should be paid to the identification of MDS/MPN. In addition to basic cell morphology, mutational analysis using next-generation sequencing plays an increasingly important role in the differential diagnosis. aCML with concomitant JAK2 V617F and SETBP1 mutations has been rarely reported, and targeted therapy for mutated JAK2 may benefit patients, especially those not suitable recipients of hematopoietic stem cell transplants.

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