2024
Clonal cytopenia of undetermined significance: definitions, risk and therapeutic targets
Taborda C, Zeidan A, Mendez L. Clonal cytopenia of undetermined significance: definitions, risk and therapeutic targets. Frontiers In Hematology 2024, 3: 1419323. DOI: 10.3389/frhem.2024.1419323.Peer-Reviewed Original ResearchClonal hematopoiesis of indeterminate potentialClonal hematopoiesisClonal cytopeniaSomatic genetic alterationsTherapeutic targetStem/progenitor cell populationsRisk stratification toolBlood of individualsMyeloid malignanciesMyeloid neoplasmsHematologic malignanciesPotential therapeutic targetIndeterminate potentialRisk stratificationBlood countGenetic alterationsStratification toolClinical investigationNatural historyCell populationsCytopeniasMalignancyBloodRiskCytopenia(sRisk Prediction for Clonal Cytopenia: Multicenter Real-World Evidence
Xie Z, Komrokji R, Al Ali N, Smith A, Geyer S, Patel A, Saygin C, Zeidan A, Bewersdorf J, Mendez L, Kishtagari A, Zeidner J, Coombs C, Madanat Y, Chung S, Badar T, Foran J, Desai P, Tsai C, Griffiths E, Al Malki M, Amanam I, Lai C, Deeg H, Ades L, Yi C, Osman A, Dinner S, Abaza Y, Taylor J, Chandhok N, Soong D, Brunner A, Carraway H, Singh A, Elena C, Ferrari J, Gallì A, Pozzi S, Padron E, Patnaik M, Malcovati L, Savona M, Al-Kali A. Risk Prediction for Clonal Cytopenia: Multicenter Real-World Evidence. Blood 2024 PMID: 38996210, DOI: 10.1182/blood.2024024756.Peer-Reviewed Original ResearchMyeloid neoplasmsIncidence of MNClonal cytopeniaCumulative incidencePlatelet count <High-risk mutationsCox proportional hazards modelsVariant allele fractionProportional hazards modelClinical trial designCCUS patientsStratify patientsGray's testC-indexDisease entityRisk groupsCytopeniasAllele fractionSomatic mutationsRisk factorsHigh riskNatural historyRisk scoreHazards modelPatientsHypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML
Shimony S, Bewersdorf J, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos Perez J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML. Leukemia 2024, 38: 762-768. PMID: 38378841, DOI: 10.1038/s41375-024-02175-0.Peer-Reviewed Original ResearchAssociated with improved OSHypomethylating agentsCPX-351Overall survivalSplicing factor mutationsCo-mutationsAllogeneic hematopoietic stem cell transplantationAssociated with better OSAssociated with worse OSSecondary acute myeloid leukemiaHematopoietic stem cell transplantationMedian overall survivalStem cell transplantationPatients aged >Acute myeloid leukemiaTreated with daunorubicinLiposomal daunorubicinMonosomal karyotypeNRAS/KRAS mutationsImproved OSSecondary AMLMyeloid diseasesMyeloid neoplasmsAML patientsAML treatment
2023
Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution
Santinelli E, Pascale M, Xie Z, Badar T, Stahl M, Bewersdorf J, Gurnari C, Zeidan A. Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution. Blood Reviews 2023, 62: 101130. PMID: 37679263, DOI: 10.1016/j.blre.2023.101130.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid malignanciesLeukemia cell survivalBcl-2 signalingPro-apoptotic agentsClinical studiesMyeloid leukemiaMyeloid neoplasmsTherapeutic revolutionMolecular alterationsMyeloid neoplasiaTherapeutic landscapeSpecific drugsApoptosis dysregulationSynergistic efficacyNew drugsMechanism of apoptosisDrugsMalignancyCombination strategiesCell survivalAttractive targetApoptotic pathwayTreatmentApoptosisOral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress
Venugopal S, Shallis R, Zeidan A. Oral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress. Expert Review Of Anticancer Therapy 2023, 23: 903-911. PMID: 37470508, DOI: 10.1080/14737140.2023.2238897.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaOral therapyMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationDisease-related complicationsDisease-directed therapyStem cell transplantationQuality of lifeCC-486HR-MDSOral azacitidineClinic visitsMost patientsGood tolerabilityIntensive therapyOptimal regimensCell transplantationTherapy combinationsTreatment optionsMedication administrationPatient outcomesMyeloid neoplasmsClinical developmentMyeloid malignanciesSpectrum 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 gapsRiskHematopoiesisCytopeniasNeoplasmsSyndromeEvolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms
Stempel J, Xie Z, Bewersdorf J, Stahl M, Zeidan A. Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms. The Cancer Journal 2023, 29: 203-211. PMID: 37195777, DOI: 10.1097/ppo.0000000000000666.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInternational Working Group response criteriaResponse criteriaPhase III clinical trialsIWG 2006 criteriaRisk of progressionPatient-focused outcomesClonal myeloid neoplasmsAcute myeloid leukemiaTherapeutic response assessmentPatient-centered responsesNovel drug developmentHematologic recoveryProgressive cytopeniasClinical trialsIWG criteriaLong-term benefitsMyeloid leukemiaIneffective hematopoiesisMyeloid neoplasmsResponse assessmentDisease severityWhat’s Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach
Awada H, Gurnari C, Xie Z, Bewersdorf J, Zeidan A. What’s Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach. Cancers 2023, 15: 2248. PMID: 37190176, PMCID: PMC10137017, DOI: 10.3390/cancers15082248.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaMDS/AML patientsEarly clinical trialsPotential therapeutic agentAML patientsMultidrug combinationsClinical trialsMyeloid leukemiaMyeloid neoplasmsRational approachSingle agentCurrent managementTherapeutic potentialStandardized guidelinesTherapeutic agentsMutational characteristicsPatientsNeoplasmsLatest findingsGenomic factorsCellular adaptationAgentsHMA resistanceFailureLeukemiaHow I treat AML incorporating the updated classifications and guidelines
Chaer F, Hourigan C, Zeidan A. How I treat AML incorporating the updated classifications and guidelines. Blood 2023, 141: 2813-2823. PMID: 36758209, PMCID: PMC10447497, DOI: 10.1182/blood.2022017808.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaClinical treatment guidelinesDaily clinical practiceInternational consensus classificationSomatic genetic abnormalitiesGerm-line predispositionWorld Health OrganizationTreatment guidelinesEuropean LeukemiaNetRisk stratificationHematologic malignanciesMyeloid leukemiaNovel therapiesMyeloid neoplasmsResponse assessmentClinical practiceNew treatmentsAML biologyConsensus classificationGenetic abnormalitiesTesting guidelinesHealth OrganizationGenetic driversRecent updatesTreatment
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 frequenciesTreatment of myelodysplastic syndromes in the era of precision medicine and immunomodulatory drugs: a focus on higher-risk disease
Mohty R, Al Hamed R, Bazarbachi A, Brissot E, Nagler A, Zeidan A, Mohty M. Treatment of myelodysplastic syndromes in the era of precision medicine and immunomodulatory drugs: a focus on higher-risk disease. Journal Of Hematology & Oncology 2022, 15: 124. PMID: 36045390, PMCID: PMC9429775, DOI: 10.1186/s13045-022-01346-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk diseaseMyelodysplastic syndromeAcute myeloid leukemiaHeterogeneous clonal diseaseHematopoietic cell transplantationRisk of progressionDifferent hematologic malignanciesImmune therapyImmunomodulatory drugsCell transplantationHematologic malignanciesMyeloid leukemiaNovel therapiesMyeloid neoplasmsTherapeutic approachesClonal diseaseDisease pathophysiologyDiseasePrecision medicineSyndromeTherapyVariable degreesCytopeniasTransplantationMalignancy
2021
Characteristics and Clinical Outcome of Patients with Clonal Cytopenias of Undetermined Significance: A Large Retrospective Multi-Center International Study
Xie Z, Hyun M, Komrokji R, Zeidan A, Madanat Y, Zeidner J, Coombs C, Griffiths E, Lai C, Kishtagari A, Foran J, Badar T, Yi C, Desai P, Ades L, Osman A, Taylor J, Deeg H, Brunner A, Carraway H, Al Ali N, Bewersdorf J, Prebet T, Singh A, Tsai C, Chandhok N, Soong D, Patnaik M, Savona M, Al-Kali A. Characteristics and Clinical Outcome of Patients with Clonal Cytopenias of Undetermined Significance: A Large Retrospective Multi-Center International Study. Blood 2021, 138: 2158. DOI: 10.1182/blood-2021-146254.Peer-Reviewed Original ResearchClinical Trials CommitteeProgression-free survivalIndependent review committeeOverall survivalTrials CommitteeDisease progressionBristol-Myers SquibbMyeloid neoplasmsResponse rateFunctional pathway analysisSpeakers bureauUndetermined significanceMultivariable modelClonal cytopeniaReview CommitteeMedian progression-free survivalBoehringer IngelheimAdvisory CommitteeMulti-centre international studyCG abnormalitiesCox proportional hazards modelGene panelDaiichi SankyoBaseline clinical dataKaplan-Meier methodImmune and Epigenetic Landscape of TP53-mutated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS)
Zeidan A, Bewersdorf J, Hasle V, Thompson E, de Menezes D, Rose S, Boss I, Fox B. Immune and Epigenetic Landscape of TP53-mutated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS). Blood 2021, 138: 3371. DOI: 10.1182/blood-2021-146329.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeAcute myeloid leukemiaBristol-Myers SquibbCurrent equity holderPoor-risk cytogeneticsVariant allele frequencyAML ptsOverall response rateTrials CommitteeMedian OSTP53 mutationsMyeloid neoplasmsFlow cytometryPeripheral bloodT cell genesHigh expressionBone marrowAverage variant allele frequencyRandomized phase 2 studyBone marrow flow cytometryT-cell gene signatureTumor cellsBM blast percentageIPSS-R score
2020
Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts
Zeidan AM, Boddu PC, Patnaik MM, Bewersdorf JP, Stahl M, Rampal RK, Shallis R, Steensma DP, Savona MR, Sekeres MA, Roboz GJ, DeAngelo DJ, Schuh AC, Padron E, Zeidner JF, Walter RB, Onida F, Fathi A, DeZern A, Hobbs G, Stein EM, Vyas P, Wei AH, Bowen DT, Montesinos P, Griffiths EA, Verma AK, Keyzner A, Bar-Natan M, Navada SC, Kremyanskaya M, Goldberg AD, Al-Kali A, Heaney ML, Nazha A, Salman H, Luger S, Pratz KW, Konig H, Komrokji R, Deininger M, Cirici BX, Bhatt VR, Silverman LR, Erba HP, Fenaux P, Platzbecker U, Santini V, Wang ES, Tallman MS, Stone RM, Mascarenhas J. Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts. The Lancet Haematology 2020, 7: e601-e612. PMID: 32563283, PMCID: PMC7302757, DOI: 10.1016/s2352-3026(20)30205-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute leukemiaMyeloid neoplasmsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2COVID-19 pandemicClinical trial participationSyndrome coronavirus 2Care of patientsPost-infection outcomesGlobal public health crisisHealth care infrastructureInternational expertsAdult patientsPublic health crisisSupportive careCoronavirus 2Trial participationHigh-income countriesOngoing COVID-19 pandemicGeneral populationPatientsHealth care environmentNeoplasmsLeukemia
2019
Myeloid disorders after autoimmune disease
Boddu P, Zeidan AM. Myeloid disorders after autoimmune disease. Best Practice & Research Clinical Haematology 2019, 32: 74-88. PMID: 30927978, PMCID: PMC6541412, DOI: 10.1016/j.beha.2019.02.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAutoimmune diseasesMyeloid neoplasmsTherapy exposureAnti-tumor necrosis factor-alpha inhibitorsNecrosis factor-alpha inhibitorsPlausible biologic mechanismsAnti-rheumatic drugsChronic immune stimulationSystemic lupus erythematosusBone marrow infiltrationMN developmentInflammatory bowel disordersAcute myeloid leukemiaAD typeDuration of exposureMN pathogenesisParaclinical featuresBowel disordersLupus erythematosusMarrow infiltrationLymphoproliferative disordersRheumatoid arthritisMultiple sclerosisMyelodysplastic syndromeExcess risk
2018
Epidemiology of myelodysplastic syndromes: Why characterizing the beast is a prerequisite to taming it
Zeidan AM, Shallis RM, Wang R, Davidoff A, Ma X. Epidemiology of myelodysplastic syndromes: Why characterizing the beast is a prerequisite to taming it. Blood Reviews 2018, 34: 1-15. PMID: 30314642, DOI: 10.1016/j.blre.2018.09.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCase ascertainmentAllogeneic hematopoietic stem cell transplantationAnnual age-adjusted incidenceHematopoietic stem cell transplantationOutcomes of patientsAge-adjusted incidenceStem cell transplantationAcute myeloid leukemiaTraditional morphologic assessmentClassification of MDSVariable cytopeniasCell transplantationMyelodysplastic syndromePrior receiptInefficient hematopoiesisEffective therapyMale genderRisk factorsMyeloid leukemiaEpidemiological trendsTreatment decisionsMyeloid neoplasmsEpidemiological assessmentDiagnostic criteriaTemporal improvement
2017
Risk of myeloid neoplasms after radiotherapy among older women with localized breast cancer: A population-based study
Zeidan AM, Long JB, Wang R, Hu X, Yu JB, Huntington SF, Abel GA, Mougalian SS, Podoltsev NA, Gore SD, Gross CP, Ma X, Davidoff AJ. Risk of myeloid neoplasms after radiotherapy among older women with localized breast cancer: A population-based study. PLOS ONE 2017, 12: e0184747. PMID: 28902882, PMCID: PMC5597231, DOI: 10.1371/journal.pone.0184747.Peer-Reviewed Original ResearchConceptsBreast cancer survivorsMyeloid neoplasmsCancer survivorsBreast cancerOlder womenOlder breast cancer survivorsTherapy-related myeloid neoplasmsCompeting-risks survival analysisAbsolute risk increaseBenefits of radiotherapyPopulation-based studyAbsence of chemotherapyRisk of developmentMultiple sensitivity analysesEligible patientsSubsequent chemotherapyAdjuvant radiotherapyLocalized diseaseCumulative incidenceInitial treatmentSEER registryPoor outcomeTreatment recommendationsMedicare claimsMN diagnosisLenalidomide use in myelodysplastic syndromes: Insights into the biologic mechanisms and clinical applications
Stahl M, Zeidan AM. Lenalidomide use in myelodysplastic syndromes: Insights into the biologic mechanisms and clinical applications. Cancer 2017, 123: 1703-1713. PMID: 28192601, DOI: 10.1002/cncr.30585.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaProlong survivalLow-risk MDSLR-MDS patientsEfficacy of lenalidomideImpressive clinical activityRecent clinical dataClonal myeloid neoplasmsMechanism of actionBlood cytopeniasConventional careTransfusion independenceCytogenetic responseClinical activityMyeloid leukemiaClinical dataIneffective hematopoiesisMyeloid neoplasmsDelay progressionHigh riskLenalidomidePatientsVariable riskHeterogeneous groupProgression
2015
Secondary Myeloid Neoplasms in Older Women with Breast Cancer after Radiotherapy: A Population-Based Study
Zeidan A, Long J, Wang R, Yu J, Hall J, Abel G, Gore S, Gross C, Ma X, Davidoff A. Secondary Myeloid Neoplasms in Older Women with Breast Cancer after Radiotherapy: A Population-Based Study. Blood 2015, 126: 1676. DOI: 10.1182/blood.v126.23.1676.1676.Peer-Reviewed Original ResearchTherapy-related myeloid neoplasmsMDS/acute myeloid leukemiaSingle-modality radiotherapyAcute myeloid leukemiaBreast cancer patientsMonths of diagnosisEarly breast cancerCompeting-risk analysisMyelodysplastic syndromeBreast cancerCancer patientsBreast cancer diagnosisRisk factorsMyeloid neoplasmsRadiation therapyAML/myelodysplastic syndromeFemale breast cancer patientsNational Cancer Institute's SurveillanceRadiotherapy-treated patientsReceipt of radiotherapySecondary myeloid neoplasmsRetrospective cohort studyCancer diagnosisNumber of comorbiditiesBetter overall survivalAzacitidine with or without Entinostat for the treatment of therapy‐related myeloid neoplasm: further results of the E1905 North American Leukemia Intergroup study
Prebet T, Sun Z, Ketterling RP, Zeidan A, Greenberg P, Herman J, Juckett M, Smith MR, Malick L, Paietta E, Czader M, Figueroa M, Gabrilove J, Erba HP, Tallman MS, Litzow M, Gore SD, intergroup T. Azacitidine with or without Entinostat for the treatment of therapy‐related myeloid neoplasm: further results of the E1905 North American Leukemia Intergroup study. British Journal Of Haematology 2015, 172: 384-391. PMID: 26577691, PMCID: PMC4794257, DOI: 10.1111/bjh.13832.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsAzacitidineBenzamidesDrug Administration ScheduleFemaleHumansKaplan-Meier EstimateLeukemia, Myeloid, AcuteMaleMiddle AgedMyelodysplastic SyndromesNeoplasms, Second PrimaryPyridinesTreatment OutcomeConceptsTherapy-related myeloid neoplasmsMyeloid neoplasmsDe novo MDS/AMLRandomized phase 2 studyCombination of azacitidineLeukemia intergroup studyMedian overall survivalPhase 2 studyMDS/AMLSerious late effectsHistone deacetylase inhibitor entinostatAZA monotherapyCombination armNormalization rateOverall survivalIntergroup studyTreatment of cancerPoor responseLate effectsMedian numberAzacitidinePatientsSingle agentResponse rateConventional treatment