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 StatementsMeSH KeywordsAntineoplastic AgentsApoptosisHumansLeukemia, Myeloid, AcuteMyeloproliferative DisordersConceptsAcute 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 pathwayTreatmentApoptosisPhase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies
Patel M, Donnellan W, Byrne M, Asch A, Zeidan A, Baer M, Fathi A, Kuykendall A, Zheng F, Walker C, Cheng L, Marando C, Savona M. Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies. Clinical Lymphoma Myeloma & Leukemia 2023, 23: 674-686. PMID: 37290996, DOI: 10.1016/j.clml.2023.05.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsHematologic NeoplasmsHumansLeukemia, Myeloid, AcutePrimary MyelofibrosisConceptsTreatment-emergent adverse eventsDose-limiting toxicityAdvanced hematologic malignanciesAcute myeloid leukemiaMyelodysplastic syndromeHematologic malignanciesCare agentsHigh-risk myelodysplastic syndromeMDS/myeloproliferative neoplasmPhase 1/2 studyEffective combination strategiesAdverse eventsComplete responseLymphoproliferative neoplasmsWeek 12Multiple myelomaSpleen volumeAcute leukemiaMyeloid leukemiaPreclinical modelsPatientsMyeloproliferative neoplasmsMoloney murine leukemia virus (PIM) kinasesMyelofibrosisKinase inhibitors
2022
Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax. Leukemia Research 2022, 122: 106942. PMID: 36108424, DOI: 10.1016/j.leukres.2022.106942.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaIDH2 inhibitorsMyeloid leukemiaResponse rateRetrospective cohort studyOverall response rateRAS pathway mutationsNovel therapeutic strategiesMedian OSR AMLCohort studyShorter OSLandmark trialsTargeted agentsFrontline treatmentMutant FLT3Combination therapyTreatment optionsIDH1/2 inhibitorsDisease progressionTherapeutic strategiesPatientsSmall molecule inhibitorsVenetoclaxTherapy
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 classificationPatientsSyndromeTherapyTreatmentGuidelinesTherapy-related myelodysplastic syndromes, or are they?
Zahr A, Kavi AM, Mukherjee S, Zeidan AM. Therapy-related myelodysplastic syndromes, or are they? Blood Reviews 2016, 31: 119-128. PMID: 27923516, DOI: 10.1016/j.blre.2016.11.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTherapy-related myelodysplastic syndromeMyelodysplastic syndromeAccurate risk stratificationManagement of patientsCounseling of patientsEffective prevention strategiesForms of MDCurrent clinical toolsRisk stratificationCancer survivorsPrior receiptRadiation monotherapyPatientsPrevention strategiesTherapeutic interventionsClinical decisionClinical toolSyndromeIndividual outcomesDe novoMonotherapyChemotherapyRadiotherapyPrognosticationIncidenceModest improvement in survival of patients with refractory anemia with excess blasts in the hypomethylating agents era in the United States
Zeidan AM, Wang R, Gross CP, Gore SD, Huntington SF, Prebet T, Abel GA, Davidoff AJ, Ma X. Modest improvement in survival of patients with refractory anemia with excess blasts in the hypomethylating agents era in the United States. Leukemia & Lymphoma 2016, 58: 982-985. PMID: 27558206, DOI: 10.1080/10428194.2016.1214954.Peer-Reviewed Original Research
2015
Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides
Zeidan AM, Sekeres MA, Garcia-Manero G, Steensma DP, Zell K, Barnard J, Ali NA, Zimmerman C, Roboz G, DeZern A, Nazha A, Jabbour E, Kantarjian H, Gore SD, Maciejewski JP, List A, Komrokji R. Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides. Leukemia 2015, 30: 649-657. PMID: 26464171, PMCID: PMC4775363, DOI: 10.1038/leu.2015.283.Peer-Reviewed Original ResearchConceptsInternational Prognostic Scoring SystemPrognostic scoring systemMD Anderson Prognostic Scoring SystemMyelodysplastic syndromePrognostic toolScoring systemDifferent prognostic scoring systemsHigh-risk myelodysplastic syndromeRelative prognostic performanceOutcomes of patientsFirst-line therapyRisk stratification toolHigh-risk groupWorld Health OrganizationHR-MDSMedian OSObjective responseOverall survivalStandard therapyPrognostic utilityStratification toolPatient cohortPrognostic performancePatientsHealth OrganizationLenalidomide Treatment for Lower Risk Nondeletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Before Azacitidine
Zeidan AM, Ali N, Padron E, Lancet J, List A, Komrokji RS. Lenalidomide Treatment for Lower Risk Nondeletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Before Azacitidine. Clinical Lymphoma Myeloma & Leukemia 2015, 15: 705-710. PMID: 26440749, DOI: 10.1016/j.clml.2015.08.083.Peer-Reviewed Original ResearchConceptsLower-risk myelodysplastic syndromesFirst-line therapyErythropoiesis-stimulating agentsFailure of treatmentTreatment failureInternational Working Group 2006 criteriaResponse rateSecond-line therapyMyelodysplastic syndrome patientsHigh response rateChromosome 5q deletionAzacitidine useHematologic improvementLenalidomide treatmentOverall survivalAnemic patientsMyelodysplastic syndromeSyndrome patientsLarge cohortLenalidomideAzacitidinePatientsLeukemic progressionClinical databaseTherapy
2014
Real-Life Experience of a Brief Arsenic Trioxide-Based Consolidation Chemotherapy in the Management of Acute Promyelocytic Leukemia: Favorable Outcomes With Limited Anthracycline Exposure and Shorter Consolidation Therapy
Leech M, Morris L, Stewart M, Smith BD, Bashey A, Holland K, Solomon S, Zhang X, Carraway HE, Pratz K, Gore SD, Zeidan AM. Real-Life Experience of a Brief Arsenic Trioxide-Based Consolidation Chemotherapy in the Management of Acute Promyelocytic Leukemia: Favorable Outcomes With Limited Anthracycline Exposure and Shorter Consolidation Therapy. Clinical Lymphoma Myeloma & Leukemia 2014, 15: 292-297. PMID: 25499624, PMCID: PMC4409502, DOI: 10.1016/j.clml.2014.11.001.Peer-Reviewed Original ResearchConceptsAcute promyelocytic leukemiaHigh-risk acute promyelocytic leukemiaConsolidation chemotherapyConsolidation therapyPromyelocytic leukemiaEffective consolidation therapyEvent-free survivalLeukemia-free survivalTrans retinoic acidArsenic trioxide combinationsChemotherapy regimenAnthracycline exposureOverall survivalSecondary malignanciesCardiac toxicityFavorable outcomeRetrospective analysisArsenic trioxideTherapyRetinoic acidChemotherapyPatientsSurvivalLeukemiaMonthsBeyond hypomethylating agents failure in patients with myelodysplastic syndromes
Zeidan AM, Kharfan-Dabaja MA, Komrokji RS. Beyond hypomethylating agents failure in patients with myelodysplastic syndromes. Current Opinion In Hematology 2014, 21: 123-130. PMID: 24335709, PMCID: PMC4124617, DOI: 10.1097/moh.0000000000000016.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsAzacitidineDNA MethylationHematopoietic Stem Cell TransplantationHumansInduction ChemotherapyLenalidomideMolecular Targeted TherapyMyelodysplastic SyndromesPrognosisRecurrenceRetreatmentThalidomideTransplantation, HomologousTreatment FailureTreatment OutcomeConceptsMyelodysplastic syndromeAllogeneic stem cell transplantationPathogenesis of MDSOnly curative modalityStem cell transplantationCombination treatment strategiesCombination therapeutic strategiesNovel therapeutic approachesHMA failureHMA therapyCurative modalityObjective responseRelapse rateDismal prognosisProlong survivalInvestigational agentsModest efficacyCell transplantationClinical trialsTreatment strategiesTherapeutic approachesTherapeutic strategiesBiologic underpinningsMost respondersMolecular pathways