2023
When to use which molecular prognostic scoring system in the management of patients with MDS?
Kewan T, Bewersdorf J, Gurnari C, Xie Z, Stahl M, Zeidan A. When to use which molecular prognostic scoring system in the management of patients with MDS? Best Practice & Research Clinical Haematology 2023, 36: 101517. PMID: 38092484, DOI: 10.1016/j.beha.2023.101517.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInternational Prognostic Scoring SystemPrognostic scoring systemAcute myeloid leukemiaScoring systemRisk stratificationRecurrent molecular alterationsHigh-risk patientsAppropriate risk stratificationManagement of patientsRecurrent genetic mutationsIntensive therapyMyeloid leukemiaTreatment strategiesPrognostic toolDisease pathogenesisMolecular alterationsHematopoietic cancersClinical decisionHeterogeneous groupGenetic mutationsNext-generation sequencingPrognostic systemPatientsVariable propensitySubsequent revisionEpidemiology and Pathogenesis of Myelodysplastic Syndrome
Rotter L, Shimony S, Ling K, Chen E, Shallis R, Zeidan A, Stahl M. Epidemiology and Pathogenesis of Myelodysplastic Syndrome. The Cancer Journal 2023, 29: 111-121. PMID: 37195766, DOI: 10.1097/ppo.0000000000000665.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeClonal hematopoiesisMDS pathophysiologyFrank MDSOutcomes of patientsOngoing clinical trialsAcute myeloid leukemiaIndividualized therapeutic approachesRisk assessment toolVariable cytopeniasOverall incidenceUnderlying pathophysiologyClinical trialsIneffective hematopoiesisMyeloid leukemiaNovel therapiesClonal cytopeniaTherapeutic modalitiesClonal disorderTherapeutic approachesUnique molecular profileEpidemiological assessmentDisease evolutionUnknown significancePathophysiologySpectrum From Clonal Hematopoiesis to Myelodysplastic Neoplasm/Syndromes and Other Myeloid Neoplasms
Xie Z, Chen E, Mendez L, Komrokji R, Zeidan A. Spectrum From Clonal Hematopoiesis to Myelodysplastic Neoplasm/Syndromes and Other Myeloid Neoplasms. The Cancer Journal 2023, 29: 130-137. PMID: 37195768, DOI: 10.1097/ppo.0000000000000656.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsClonal hematopoiesisHigh-risk patientsRisk of progressionSuch patientsUndetermined significanceAge-related diseasesHematologic malignanciesClonal cytopeniaMyeloid neoplasmsHigh riskUnmet needMyeloid malignanciesNatural historyCH managementPatientsMalignancySignificant knowledge gapsRiskHematopoiesisCytopeniasNeoplasmsSyndromeWhy do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS
Frumm S, Shimony S, Stone R, DeAngelo D, Bewersdorf J, Zeidan A, Stahl M. Why do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS. Blood Reviews 2023, 60: 101056. PMID: 36805300, DOI: 10.1016/j.blre.2023.101056.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeDNA methyltransferase inhibitorLow risk (LR) MDSHigh-risk myelodysplastic syndromeHigh transfusion needsRisk myelodysplastic syndromesCurrent treatment landscapeErythropoiesis-stimulating agentsNovel drug developmentHR-MDSTreatment landscapeTransfusion needsTargetable mutationsClinical trialsMDS pathogenesisNew agentsRing sideroblastsMore drugsUnmet needTherapy developmentDrug developmentMethyltransferase inhibitorFactor mutationsApprovalInflammationAn overview of novel therapies in advanced clinical testing for acute myeloid leukemia
Venugopal S, Xie Z, Zeidan A. An overview of novel therapies in advanced clinical testing for acute myeloid leukemia. Expert Review Of Hematology 2023, 16: 109-119. PMID: 36718500, DOI: 10.1080/17474086.2023.2174521.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBridged Bicyclo Compounds, HeterocyclicHumansLeukemia, Myeloid, AcuteMutationRecurrenceConceptsAML therapyMolecular pathogenesisApproval of midostaurinPathophysiology of AMLMeasurable residual diseaseAdvanced clinical testingClinical trial developmentAcute myeloid leukemiaCell surface antigensDevelopment of agentsDisease relapseImmune environmentAML treatmentResidual diseaseTherapeutic armamentariumMyeloid leukemiaNovel therapiesSurface antigenClinical testingTrial developmentTherapyAMLEscape mechanismsGene mutationsRelapse
2022
TP53-altered higher-risk myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a distinct genetic entity with unique unmet needs
Ball S, Loghavi S, Zeidan A. TP53-altered higher-risk myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a distinct genetic entity with unique unmet needs. Leukemia & Lymphoma 2022, 64: 540-550. PMID: 36323304, DOI: 10.1080/10428194.2022.2136969.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyelodysplastic syndromeVariant allele frequencyMyeloid leukemiaMDS/acute myeloid leukemiaIndependent poor prognostic factorBCL2 inhibitor venetoclaxPoor prognostic factorDisease-modifying therapiesIntensive chemotherapyBlast countClinical coursePrognostic factorsInvestigational agentsDisease entityClinical studiesInhibitor venetoclaxMyeloid neoplasmsResponse ratePathogenic alterationsNeoplasmsDistinct genetic entitiesLeukemiaGenetic characteristicsAllele frequenciesCHIPing away the progression potential of CHIP: A new reality in the making
Xie Z, Zeidan AM. CHIPing away the progression potential of CHIP: A new reality in the making. Blood Reviews 2022, 58: 101001. PMID: 35989137, DOI: 10.1016/j.blre.2022.101001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsClonal hematopoiesisEffective preventive strategiesEvidence-based recommendationsClinical sequelaeInterventional trialsClinical outcomesClinical trialsPreventive strategiesInterventional strategiesProgression potentialClinical implicationsIndeterminate potentialTrialsMolecular mechanismsLatest updatesHematopoiesisUrgent needIn vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Leukemia 2022, 36: 1313-1323. PMID: 35273342, PMCID: PMC9103411, DOI: 10.1038/s41375-022-01536-x.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeMDS/acute myeloid leukemiaRefractory acute myeloid leukemiaPARP inhibitionVivo anti-tumor effectsAlternate therapeutic optionsSubset of AMLAnti-tumor effectsPre-clinical studiesRibose polymerase inhibitorsSerial transplantation assaysHomologous recombination defectsTherapeutic optionsTreatment optionsOverall engraftmentHigh relapseIDH inhibitionMyeloid leukemiaIsocitrate dehydrogenase 1Small molecule inhibitorsCell frequencyXeno-graftsIDH1/2 mutationsMalignant transformation
2021
Gilteritinib vs salvage chemotherapy in FLT3-mutated acute myeloid leukemia: number needed to treat for clinical outcomes per a secondary analysis of the ADMIRAL trial
Zeidan AM, Qi CZ, Yang H, Garnham A, Shah MV, Pandya BJ. Gilteritinib vs salvage chemotherapy in FLT3-mutated acute myeloid leukemia: number needed to treat for clinical outcomes per a secondary analysis of the ADMIRAL trial. Leukemia & Lymphoma 2021, 63: 762-764. PMID: 34749571, DOI: 10.1080/10428194.2021.2001467.Peer-Reviewed Original ResearchEnasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial
DiNardo CD, Schuh AC, Stein EM, Montesinos P, Wei AH, de Botton S, Zeidan AM, Fathi AT, Kantarjian HM, Bennett JM, Frattini MG, Martin-Regueira P, Lersch F, Gong J, Hasan M, Vyas P, Döhner H. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. The Lancet Oncology 2021, 22: 1597-1608. PMID: 34672961, DOI: 10.1016/s1470-2045(21)00494-0.Peer-Reviewed Original ResearchMeSH KeywordsAgedAminopyridinesAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsAzacitidineDrug Administration ScheduleDrug-Related Side Effects and Adverse ReactionsFemaleHumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcuteMaleMutationProgression-Free SurvivalRandom AllocationTreatment OutcomeTriazinesConceptsAcute myeloid leukemiaSerious treatment-related adverse eventsTreatment-related adverse eventsDose-finding portionOverall response rateMyeloid leukemiaAdverse eventsFebrile neutropeniaCombination groupInterim analysisEastern Cooperative Oncology Group performance statusCommon treatment-related grade 3Response rateInteractive web response systemTreatment-related grade 3Phase 1b/2 trialPrespecified interim analysisTreatment-related deathsPhase 2 trialWeb response systemPhase 2Acute myeloid leukemia subtypesPhase 2 portionBristol-Myers SquibbAzacitidine monotherapy
2020
A complex karyotype and a genetic mutation in acute myeloid leukaemia
Bewersdorf JP, Siddon A, DiAdamo A, Zeidan AM. A complex karyotype and a genetic mutation in acute myeloid leukaemia. The Lancet 2020, 396: 2018. PMID: 33341145, DOI: 10.1016/s0140-6736(20)32543-5.Peer-Reviewed Original ResearchWide variation in use and interpretation of gene mutation profiling panels among health care providers of patients with myelodysplastic syndromes: results of a large web-based survey
Pine AB, Chokr N, Stahl M, Steensma DP, Sekeres MA, Litzow MR, Luger SM, Stone RM, Greenberg PL, Bejar R, Bewersdorf JP, Gore SD, Zeidan AM. Wide variation in use and interpretation of gene mutation profiling panels among health care providers of patients with myelodysplastic syndromes: results of a large web-based survey. Leukemia & Lymphoma 2020, 61: 1455-1464. PMID: 32026740, DOI: 10.1080/10428194.2020.1723013.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromeRisk stratificationMolecular profilingNext-generation sequencingWeb-based surveyRole of NGSManagement of patientsUtility of NGSEvidence-based guidelinesHealth care providersLarge web-based surveyMDS patientsPractice patternsTreatment decisionsCare providersResponse assessmentProviders' beliefsPatientsInstitutional guidelinesGene mutationsDiagnosisSyndromeTesting logisticsInterpretation of resultsWide variation
2018
Aplastic anemia: Etiology, molecular pathogenesis, and emerging concepts
Shallis RM, Ahmad R, Zeidan AM. Aplastic anemia: Etiology, molecular pathogenesis, and emerging concepts. European Journal Of Haematology 2018, 101: 711-720. PMID: 30055055, DOI: 10.1111/ejh.13153.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAplastic anemiaMolecular pathogenesisDevelopment of AAStem cell injuryHematopoietic stem cell injuryT cell homeostasisTelomerase complex genesBone marrow failureLikely autoimmuneMarrow featuresPeripheral cytopeniasPathologic featuresPatient outcomesMonosomy 7Rare disorderAA pathogenesisCell injuryPathogenic mechanismsTrisomy 8Clonal diseaseCytogenetic abnormalitiesPathogenesisMarrow failureDiseaseUniparental disomyThe genetic and molecular pathogenesis of myelodysplastic syndromes
Shallis RM, Ahmad R, Zeidan AM. The genetic and molecular pathogenesis of myelodysplastic syndromes. European Journal Of Haematology 2018, 101: 260-271. PMID: 29742289, DOI: 10.1111/ejh.13092.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMolecular pathogenesisGene expression profilingSignal transduction elementsDevelopment of MDSHigh-throughput techniquesCohesin proteinsMyelodysplastic syndromeRNA splicingDNA methylationTranscription factorsDNA repairMolecular basisExpression profilingMalignant myeloid disordersBone marrow microenvironmentGenetic materialClonal architectureSuch mutationsTransduction elementsInflammatory bone marrow microenvironmentMarrow microenvironmentImportant substrateGenetic mutationsDiverse groupPathophysiology of MDS
2016
Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.
Greenberg PL, Stone RM, Al-Kali A, Barta SK, Bejar R, Bennett JM, Carraway H, De Castro CM, Deeg HJ, DeZern AE, Fathi AT, Frankfurt O, Gaensler K, Garcia-Manero G, Griffiths EA, Head D, Horsfall R, Johnson RA, Juckett M, Klimek VM, Komrokji R, Kujawski LA, Maness LJ, O'Donnell MR, Pollyea DA, Shami PJ, Stein BL, Walker AR, Westervelt P, Zeidan A, Shead DA, Smith C. Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. Journal Of The National Comprehensive Cancer Network 2016, 15: 60-87. PMID: 28040720, DOI: 10.6004/jnccn.2017.0007.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeNCCN Clinical Practice GuidelinesHigh-intensity therapyPresence of cytopeniasLow-intensity therapyClinical practice guidelinesVariable disease courseTreatment of anemiaBetter treatment guidanceSupportive careDisease courseTherapeutic optionsPractice guidelinesDiagnostic criteriaTreatment approachesMyeloid disordersHeterogenous groupMolecular abnormalitiesTreatment guidanceDiagnostic classificationPatientsSyndromeTherapyTreatmentGuidelinesClinical response to ruxolitinib in CSF3R T618-mutated chronic neutrophilic leukemia
Stahl M, Xu ML, Steensma DP, Rampal R, Much M, Zeidan AM. Clinical response to ruxolitinib in CSF3R T618-mutated chronic neutrophilic leukemia. Annals Of Hematology 2016, 95: 1197-1200. PMID: 27068405, PMCID: PMC7479634, DOI: 10.1007/s00277-016-2664-4.Peer-Reviewed Original Research
2015
The evolving field of prognostication and risk stratification in MDS: Recent developments and future directions
Lee EJ, Podoltsev N, Gore SD, Zeidan AM. The evolving field of prognostication and risk stratification in MDS: Recent developments and future directions. Blood Reviews 2015, 30: 1-10. PMID: 26119927, DOI: 10.1016/j.blre.2015.06.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeRisk stratificationRecurrent molecular mutationsRisk stratification toolRelevant clinical outcomesPrediction of outcomeRisk/benefit calculationsClinical courseClinical outcomesStratification toolMDS patientsPrognostication toolsIndividual patientsClinical practiceMolecular testingTherapeutic interventionsPatient careTherapeutic selectionPatientsMolecular mutationsIndependent impactPrognosticationBiological heterogeneityOutcomesReliable assayEpigenetic Therapy in Acute Myeloid Leukemia: Current and Future Directions
Kim TK, Gore SD, Zeidan AM. Epigenetic Therapy in Acute Myeloid Leukemia: Current and Future Directions. Seminars In Hematology 2015, 52: 172-183. PMID: 26111464, PMCID: PMC5785931, DOI: 10.1053/j.seminhematol.2015.04.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid leukemiaTreatment of AMLPathogenesis of AMLDevelopment of AMLNormal physiologic developmentHistone deacetylase inhibitorsEpigenetic therapyDNA methylationHistone methylation/acetylationTherapeutic optionsClinical evaluationDNA methyltransferase inhibitorHistone tail modificationsInhibitor of histoneMethylation/acetylationPromising drugClinical practiceTherapeutic targetingMutant isocitrate dehydrogenasesDeacetylase inhibitorsActual DNA sequenceAberrant DNA methylationPhysiologic developmentImportant mechanismCurrent state of prognostication and risk stratification in myelodysplastic syndromes
Zeidan AM, Gore SD, Padron E, Komrokji RS. Current state of prognostication and risk stratification in myelodysplastic syndromes. Current Opinion In Hematology 2015, 22: 146-154. PMID: 25575032, DOI: 10.1097/moh.0000000000000110.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsGenome sequencing in myelodysplastic syndromes: can molecular mutations predict benefit from hypomethylating agent therapy?
Lee EJ, Zeidan AM. Genome sequencing in myelodysplastic syndromes: can molecular mutations predict benefit from hypomethylating agent therapy? Expert Review Of Hematology 2015, 8: 155-158. PMID: 25697572, DOI: 10.1586/17474086.2015.1016905.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeHigh-risk myelodysplastic syndromeMolecular mutationsRecurrent molecular mutationsReliable clinical predictorsIndependent prognostic valueMyelodysplastic syndrome patientsUrgent clinical needIdentification of biomarkersAgent therapyClinical predictorsPrognostic valuePrognostic subgroupsSyndrome patientsVariable coursePatientsClinical implicationsTET2 mutationsClinical needSyndromeTherapyRecurrent mutationsBiomarkersHMAsResearch priorities