Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 140, No. 11 ( 2022-09-15), p. 1200-1228

Abstract: The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CACs) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As a continuation of this CAC-based process, the authors, a group with expertise in the clinical, pathologic, and genetic aspects of these disorders, developed the International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias. Using a multiparameter approach, the main objective of the consensus process was the definition of real disease entities, including the introduction of new entities and refined criteria for existing diagnostic categories, based on accumulated data. The ICC is aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.2022015850

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 129, No. 24 ( 2017-06-15), p. 3165-3174

Abstract: Selinexor is a novel, first-in-class, selective inhibitor of nuclear export compound, which blocks exportin 1 (XPO1) function, leads to nuclear accumulation of tumor suppressor proteins, and induces cancer cell death. A phase 1 dose-escalation study was initiated to examine the safety and efficacy of selinexor in patients with advanced hematological malignancies. Ninety-five patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to receive 4, 8, or 10 doses of selinexor in a 21- or 28-day cycle. The most frequently reported adverse events (AEs) in patients with AML were grade 1 or 2 constitutional and gastrointestinal toxicities, which were generally manageable with supportive care. The only nonhematological grade 3/4 AE, occurring in & gt;5% of the patient population, was fatigue (14%). There were no reported dose-limiting toxicities or evidence of cumulative toxicity. The recommended phase 2 dose was established at 60 mg (∼35 mg/m2) given twice weekly in a 4-week cycle based on the totality of safety and efficacy data. Overall, 14% of the 81 evaluable patients achieved an objective response (OR) and 31% percent showed ≥50% decrease in bone marrow blasts from baseline. Patients achieving an OR had a significant improvement in median progression-free survival (PFS) (5.1 vs 1.3 months; P = .008; hazard ratio [HR], 3.1) and overall survival (9.7 vs 2.7 months; P = .01; HR, 3.1) compared with nonresponders. These findings suggest that selinexor is safe as a monotherapy in patients with relapsed or refractory AML and have informed subsequent phase 2 clinical development. This trial was registered at www.clinicaltrials.gov as #NCT01607892.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2016-11-750158

Language: English

Publisher: American Society of Hematology

Publication Date: 2017

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 129, No. 24 ( 2017-06-15), p. 3175-3183

Abstract: Patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) have a poor prognosis and limited treatment options. We evaluated selinexor, an orally bioavailable, first-in-class inhibitor of the nuclear export protein XPO1, in this phase 1 trial to assess safety and determine a recommended phase 2 dose (RP2D). Seventy-nine patients with various NHL histologies, including diffuse large B-cell lymphoma, Richter’s transformation, mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia, were enrolled. In the dose-escalation phase, patients received 3 to 80 mg/m2 of selinexor in 3- or 4-week cycles and were assessed for toxicities, pharmacokinetics, and antitumor activity. In the dose-expansion phase, patients were treated with selinexor at 35 or 60 mg/m2. The most common grade 3 to 4 drug-related adverse events were thrombocytopenia (47%), neutropenia (32%), anemia (27%), leukopenia (16%), fatigue (11%), and hyponatremia (10%). Tumor biopsies showed decreases in cell-signaling pathways (Bcl-2, Bcl-6, c-Myc), reduced proliferation (Ki67), nuclear localization of XPO1 cargos (p53, PTEN), and increased apoptosis after treatment. Twenty-two (31%) of the 70 evaluable patients had an objective responses, including 4 complete responses and 18 partial responses, which were observed across a spectrum of NHL subtypes. A dose of 35 mg/m2 (60 mg) was identified as the RP2D. These findings suggest that inhibition of XPO1 with oral selinexor at 35 mg/m2 is a safe therapy with encouraging and durable anticancer activity in patients with R/R NHL. The trial was registered at www.clinicaltrials.gov as #NCT01607892.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2016-11-750174

Language: English

Publisher: American Society of Hematology

Publication Date: 2017

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4773-4773

Abstract: Introduction: The nuclear export protein exportin 1, (XPO1) is overexpressed in a wide variety of cancers including MM and often correlate with poor prognosis. Selinexor (KPT-330) is an oral Selective Inhibitor of Nuclear Export (SINE) XPO1 antagonist in Phase 1 and 2 clinical studies. Selinexor forces nuclear retention and reactivation of tumor suppressor proteins (TSPs) and reduction of many proto-oncogenes, including MDM2, MYC and Cyclin D. In addition, selinexor potently deactivates NF-κB, through forced nuclear retention of IκBα. Together these effects induce selective apoptosis in MM cells and inhibition of NF-κB dependent osteoclast activation. XPO1 is also responsible for nuclear export of the glucocorticoid receptor (GR). We hypothesized that selinexor will enhance the activity of dexamethasone (DEX)-bound GR, resulting in synergistic tumor cell killing. Methods: In vitro tumor cell viability measurements were based on MTT (CellTiter 96¨/Promega) and combination indices were calculated using CalcuSyn software. For xenograft studies, utilized NOD-SCID mice with subcutaneous inoculation of MM.1s cells. GR nuclear localization was measured with immunofluorescent anti-GR (phosphor-S211) antibody and quantitative imaging. To assess GR transcriptional activation, GR binding to a GCR consensus sequence was measured in nuclear extracts using an ELISA method (GR ELISA kit/Affymetrix). Patients (pts) with heavily pretreated refractory MM were dosed with oral selinexor at doses of up to 60 mg/m2 (8-10 doses/4 wk cycle) as part of a Phase 1 program in advanced hematological malignancies. Response we defined based on the IMWG criteria. The effect of combining DEX with selinexor was analyzed in all pts who received selinexor at moderate to high doses (30-60 mg/m2). Safety and efficacy were analyzed separately in three groups: no DEX, 〈 20 mg DEX and 20 mgs DEX. Results: In MM.1s cells Sel-Dex showed synergy for nuclear retention of the DEX activated GR (Ser211-phosphorylated) and concomitant GR transcriptional activation. Sel-Dex showed highly synergistic cytotoxicity in MM.1s cells in vitro and in vivo, with a corresponding increase in apoptosis. Selinexor alone was potently cytotoxic in the DEX resistant MM cell lines MM.1R and ANBL6, but addition of DEX provided no additional effect. Twenty-eight pts with heavily pretreated refractory MM (16 M, 12 F; median age 62; ECOG PS 0/1: 7/21; median prior regimens: 6) received selinexor at 30 – 60 mg/m2 with either 0, 〈 20, or 20 mgs DEX. All pts have received a proteasome inhibitor and an Imid and the majority of the pts have received pomalidomide (68%) and/or carfilzomib (36%). The most common Grade 1/2 AEs for these three groups were: nausea (82%/86%/70%), fatigue (55%/86%/40%), anorexia (36%/71%/60%), and vomiting (36%/57%/10%). Of the 28 pts treated; 10 heavily pretreated refractory MM pts treated with a combination of selinexor (45 mg/m2 twice weekly) and DEX (20 mg with each selinexor dose) were found to have dramatically improved disease response (n=10, ORR 60%), with one stringent complete response (sCR, 10%), 5 partial responses (PR, 50%) and clinical benefit rate (CBR) rate of 80% (Figure 1). Treatment with ³30mg/m2 selinexor and 〈 20 mg DEX (n=7), resulted in ORR of 14% and CBR of 86%, while treatment with selinexor (30-60 mg/m2) without DEX (n=12) showed best response of stable disease (50%). Sel-Dex was also associated with an increase in time on study relative to selinexor alone, with 7 of out 10 pts in the 20 mg DEX combo group still on study (11-25 weeks). Five additional pts were treated with selinexor at a dose of 60 mg/m2 in combination with 20 mg DEX. Response evaluation is pending. Conclusions: Sel-Dex combination is markedly synergistic in preclinical models, which is supported by the preliminary clinical data presented. One potential mechanism underlying this synergy is the amplification of GR activity due the combined effects of selinexor-induced nuclear retention of activated GR coupled with DEX-mediated GR agonism. These results provide a promising basis for the continuing study of Sel-Dex for treatment of pts with refractory MM. Phase 2 studies of Sel-Dex in pts with MM refractory to both pomalidomide and carfilzomib are planned for early 2015. Disclosures Chen: Celgene: Honoraria; Janssen: Honoraria. Off Label Use: Lenalidomide maintenance therapy after ASCT. Gutierrez:Senesco: PI Other. Siegel:Celgene, Millennium, Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Baz:Celgene: Research Funding; Millennium: Research Funding; Bristol Myers Squibb: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding. Kukreti:Celgene: Honoraria. Azmi:Karyopharm Therpeutics: Research Funding. Kashyap:Karyopharm Therapeutics: Employment. Landesman:Karyopharm Therapeutics: Employment. Marshall:Karyopharm Therpeutics: Employment. McCartney:Karyopharm Therpeutics: Employment. Saint-Martin:Karyopharm Therpeutics: Employment. Norori:Karyopharm Therpeutics: Consultancy. Savona:Karyopharm Therpeutics: Membership on an entity's Board of Directors or advisory committees. Rashal:Karyopharm Therapeutics: Employment. Carlson:Karyopharm Therapeutics: Employment. Mirza:Karyopharm Therpeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shacham:Karyopharm Therapeutics Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Kauffman:Karyopharm Therapeutics: Employment, Equity Ownership. Reece:Millennium: Honoraria, Research Funding; Millennium: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Merck: Research Funding; Merck: Research Funding; BMS: Research Funding; BMS: Research Funding; Novartis: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen : Honoraria; Amgen : Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.4773.4773

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 180-180

Abstract: Background: AML is an aggressive malignancy with a median age of 67 yrs at diagnosis and an age-adjusted 5-yr survival of less than 25%. Most older patients (pts) with AML have poor risk cytogenetic/genetic features associated with suboptimal complete remission (CR) rates and overall survival (OS). Until recently, the anthracycline and cytarabine based induction remained unchanged for over 4 decades. Vosaroxin (Vos) is a first-in-class anticancer quinolone derivative which is thought to induce less cardiac toxicity than standard anthracycline therapy. Vos was previously administered in combination with intermediate dose cytarabine (IDAC) in relapsed/refractory (r/r) AML pts in a large randomized phase 3 trial (VALOR) and demonstrated significantly improved CR rates compared to IDAC alone but without improvement in OS. In the VITAL study, we investigated the combination of infusional cytarabine (iAC) with Vos ("7 + V") in newly diagnosed AML. Methods: VITAL (NCT02658487) is a single-arm, open-label, two-stage phase II study of 90 mg/m2, Vos on days 1 and 4 (reduced to 70 mg/m2, days 1 and 4 in the event of re-induction) and 100 mg/m2 continuous iAC on days 1-7. Oral cryotherapy was administered during Vos administration as prophylaxis for oral mucositis seen in prior studies. Enrollment in stage 1 was limited to 17 evaluable pts & gt;55 yrs of any risk classification or pts 18-54 years with high-risk disease. The two-stage design required CR in more than 7 of the first 17 pts in order to proceed to stage 2. The operating characteristics of the study design provided a 64% probability of early termination if CR occurred in 7 or fewer pts suggesting that the true CR rate would be ≤ 40%. Stage 2 included an additional 24 pts (age 18-54 yrs with intermediate or high-risk disease, or 55 years or older with any risk disease). Response was assessed using the modified IWG-2003 criteria. Results: In total, 42 pts were enrolled and assessed for toxicity. One patient who achieved an aplastic marrow biopsy at day 14, succumbed to an AML-related sepsis event prior to formal response assessment was initially deemed unevaluable for response and replaced but was ultimately included in the response assessment. Baseline demographics of the 42 enrolled pts are seen in Table 1a. Median age was 63 yrs (range, 43-74) and 86% (36/42) were ≥ 55yrs at time of enrollment. Almost all, 40/42 (95%), had intermediate (11/40) or poor (29/40) risk AML. Adverse events (AEs) of special interest of any Grade (Gr) and Gr 3-5 AEs occurring in & gt; 10% of pts are listed in Table 1b. Oral mucositis was observed in 16/42 (38%) pts with 12/42 (29%) having Gr 1-2 and only 4/42 (10%) having Gr 3 severity. Three Gr 5 events occurred (2-Infection/Sepsis; 1-neutropenic colitis). No acute cardiac toxicity was seen. CR was achieved in 20/42 (48%) pts, while 3 additional pts achieved CR with incomplete count recovery (CRi) for a CR/CRi rate of 55% (23/42). CR was observed in 100% (2/2) with favorable risk (both & gt;65 yrs old). CR/CRi was seen in 73% (8/11) intermediate and 45% (13/29) poor risk pts. One poor risk pt with CRi converted to CR in the absence of additional therapy but did so outside of the protocol defined time period for response assessment (Day 57 +/- 3 days) and was recorded as CRi for this analysis. CR/CRi was noted in 40% (4/10) pts whose AML had TP53 mutations. Allogeneic hematopoietic stem cell transplant was performed in 45% (19/42) of pts. Progression-free survival was 43% and OS was 48% for all pts at 1-year of follow-up (Figure 1). Conclusion: The combination of Vos and iAC in newly diagnosed AML pts appears safe. Mucocutaneous complications were observed as noted in previous studies with Vos. Administration of oral cryotherapy during Vos administration appeared to reduce occurrence of oral mucositis during induction, but & gt; Gr 3 neutropenic enterocolitis occurred in 7/42 (17%) pts. Still, the combination appears to be tolerable with an adverse event profile analogous to conventional induction regimens. While the VALOR trial observed Gr 3-5 cardiac AEs in & lt; 1% of the 705 r/r AML pts with prior anthracycline exposure, no attributable cardiac events were seen within the VITAL trial population. Vosaroxin and infusional cytarabine is a clinically active induction regimen which warrants further investigation based on response rates and toxicity profile at least similar to current anthracycline based induction strategies with an apparent absence of cardiac toxicity. Disclosures Strickland: Astellas: Consultancy; Jazz: Consultancy; Kite: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Sunesis: Research Funding; AbbVie: Consultancy. Podoltsev:Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Kartos Therapeutics: Research Funding; Astellas Pharma: Research Funding; Daiichi Sankyo: Research Funding; Sunesis Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Astex Pharmaceuticals: Research Funding; CTI Biopharma: Research Funding; Celgene: Other: Grant funding, Research Funding; Genentech: Research Funding; AI Therapeutics: Research Funding; Samus Therapeutics: Research Funding; Arog Pharmaceuticals: Research Funding. Zeidan:Acceleron Pharma: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Otsuka: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Cardinal Health: Honoraria; Seattle Genetics: Honoraria; BeyondSpring: Honoraria. Byrne:Karyopharm: Research Funding. Gore:Celgene Corporation: Consultancy, Research Funding. Savona:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Patents & Royalties; AbbVie: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-131520

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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detail.hit.zdb_id: 80069-7

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. TPS6636-TPS6636

Abstract: TPS6636 Background: With more-potent tyrosine kinase inhibitors, increasingly sensitive methods are required to monitor treatment response and quantify minimal residual disease (MRD). Molecular monitoring is recommended by National Comprehensive Cancer Network and European LeukemiaNet guidelines; major molecular response (MMR) correlates with optimal long-term outcomes. CMR, while implying absence of BCR-ABL transcripts, is defined by levels undetectable by current technology (generally ≥4.5 logs reduced below a standardized baseline using quantitative real-time polymerase chain reaction [RT-PCR]). Newer technologies that can detect larger reductions will be important in analyzing correlations between decreased disease burden and long-term outcomes and may assist in selecting patients for “stopping” therapy. Methods: This US study plans to enroll 100 adults with newly diagnosed Ph+ CML-CP within 6 months of diagnosis to receive nilotinib 300 mg twice daily (BID) for up to 2 years. BCR-ABL transcripts are quantified using RT-PCR at a central laboratory. An exploratory molecular assay (digital detection [DiD] ) with an additional 〉 1-log sensitivity and mutation detection and quantification will be evaluated. Primary endpoint: the rate of confirmed CMR at 24 months (CMR confirmed by second PCR sample within 3 months; ≥4.5-log reduction of BCR-ABL from standardized baseline on the international scale [IS], equivalent to BCR-ABL ≤0.0032% IS). Dose escalation to 400 mg BID is allowed per protocol. Secondary endpoints: rate of, time to, and duration of complete cytogenetic response (CCyR), MMR, and CMR; rate of and time to loss of CCyR, MMR, and CMR and to progression to accelerated phase/blast crisis; rate of CMR in dose-escalated patients; and event-free, progression-free, and overall survival. Exploratory endpoints: BCR-ABL trends and correlation of mutations with response. The DiD assay data will provide information on BCR-ABL trends below the current CMR threshold and assist in evaluating lower levels of MRD.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/jco.2012.30.15_suppl.tps6636

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2012

detail.hit.zdb_id: 2005181-5

In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 6168-6168

Abstract: Despite a detailed understanding of the genes mutated in myelodysplastic syndromes (MDS), diagnostic and treatment decisions for patients with MDS rely primarily on clinical and cytogenetic variables as considered by the Revised International Prognostic Scoring System (IPSS-R). Here we describe the recently developed Molecular IPSS (IPSS-M), a clinico-genomic risk stratification system that considers clinical, cytogenetic and genetic parameters; the implementation of a web portal to facilitate its adoption, a strategy to handle missing variables, and the worldwide utilization of the web calculator as a clinical support tool. The IPSS-M was trained on 2,957 clinically annotated diagnostic MDS samples profiled for mutations in 156 driver genes. To maximize the clinical applicability of the IPSS-M and account for missing genetic data (i.e genes missing from a sequencing panel), we implemented a strategy to calculate a risk score under three scenarios: best, worst and average. Last, we developed an online calculator as a standalone single-page web application using VueJs, and D3Js for the interactive visualizations, deployed through a CI/CD pipeline on AWS, where collection of anonymous usage analytics allows to track adoption and usability of the new proposed model. The model incorporates clinical, morphological, genetic variables informed by cytogenetics and constructed from the presence of oncogenic mutations in 31 genes. It delivers a unique risk score for each individual patient, as well as an assignment to one of six IPSS-M risk strata. Compared to the IPSS-R the IPSS-M re-stratified 46% of MDS patients. The model was validated in an external dataset of 754 MDS patients. We released an open-access IPSS-M web calculator available at https://mds-risk-model.com. By specifying the patient clinical and molecular profiles, the tool returns the patient-specific IPSS-M risk score and category, and the probability estimates over time for three clinical endpoints, i.e. leukemia free survival (LFS), overall survival, and incidence of leukemic transformation. Since its launch in June 2022, the calculator has been used by & gt;6000 users in & gt;75 countries, reaching a daily average of 100 users per day. Risks have been calculated for & gt;45,000 patient profiles. 99.28% of the sessions initiated reach an IPSS-M score, suggesting that the calculator is intuitive and easy to use. We trained and validated the IPSS-M on 3,711 patients, a patient tailored risk stratification tool for patients with MDS that considers clinical, morphological and genetic variables inclusive of cytogenetics and mutations in one of 31 genes. The development of a web based tool was instrumental to the global dissemination of the model, enabling non-expert users to leverage the power of molecular biomarkers in risk stratification for patients with MDS. Citation Format: Elsa Bernard, Juan E. Arango Ossa, Heinz Tuechler, Peter L. Greenberg, Robert P. Hasserjian, Yasuhito Nannya, Sean M. Devlin, Maria Creignou, Philippe Pinel, Lily Monier, Juan S. Medina-Martinez, Dylan Domenico, Martin Jädersten, Ulrich Germing, Guillermo Sanz, Arjan A. van de Loosdrecht, Olivier Kosmider, Matilde Y. Follo, Felicitas Thol, Lurdes Zamora, Ronald F. Pinheiro, Andrea Pellagatti, Detlef Haase, Pierre Fenaux, Monika Belickova, Michael R. Savona, Virginia M. Klimek, Fabio P. Santos, Jacqueline Boultwood, Ioannis Kotsianidis, Valeria Santini, Francesc Solé, Uwe Platzbecker, Michael Heuser, Peter Valent, Kazuma Ohyashiki, Carlo Finelli, Maria Teresa Voso, Lee-Yung Shih, Michaela Fontenay, Joop H. Jansen, José Cervera, Norbert Gattermann, Benjamin L. Ebert, Rafael Bejar, Luca Malcovati, Mario Cazzola, Seishi Ogawa, Eva Hellström-Lindberg, Elli Papaemmanuil. Implementation and adoption of a web tool to support precision diagnostic and treatment decisions for patient with myelodysplastic syndromes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6168.

Type of Medium: Online Resource

ISSN: 1538-7445

URL: Article

DOI: 10.1158/1538-7445.AM2023-6168

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2023

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detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

In: Blood, American Society of Hematology, Vol. 140, No. 21 ( 2022-11-24), p. 2228-2247

Abstract: Myeloid neoplasms and acute leukemias derive from the clonal expansion of hematopoietic cells driven by somatic gene mutations. Although assessment of morphology plays a crucial role in the diagnostic evaluation of patients with these malignancies, genomic characterization has become increasingly important for accurate diagnosis, risk assessment, and therapeutic decision making. Conventional cytogenetics, a comprehensive and unbiased method for assessing chromosomal abnormalities, has been the mainstay of genomic testing over the past several decades and remains relevant today. However, more recent advances in sequencing technology have increased our ability to detect somatic mutations through the use of targeted gene panels, whole-exome sequencing, whole-genome sequencing, and whole-transcriptome sequencing or RNA sequencing. In patients with myeloid neoplasms, whole-genome sequencing represents a potential replacement for both conventional cytogenetic and sequencing approaches, providing rapid and accurate comprehensive genomic profiling. DNA sequencing methods are used not only for detecting somatically acquired gene mutations but also for identifying germline gene mutations associated with inherited predisposition to hematologic neoplasms. The 2022 International Consensus Classification of myeloid neoplasms and acute leukemias makes extensive use of genomic data. The aim of this report is to help physicians and laboratorians implement genomic testing for diagnosis, risk stratification, and clinical decision making and illustrates the potential of genomic profiling for enabling personalized medicine in patients with hematologic neoplasms.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.2022015853

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

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In: Leukemia Research, Elsevier BV, Vol. 65 ( 2018-02), p. 67-73

Type of Medium: Online Resource

ISSN: 0145-2126

URL: Article

DOI: 10.1016/j.leukres.2017.12.012

Language: English

Publisher: Elsevier BV

Publication Date: 2018

detail.hit.zdb_id: 2008028-1

In: Nature Medicine, Springer Science and Business Media LLC, Vol. 27, No. 3 ( 2021-03), p. 562-562

Type of Medium: Online Resource

ISSN: 1078-8956 , 1546-170X

URL: Article

DOI: 10.1038/s41591-021-01253-5

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

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