2024
Myelodysplastic Syndromes and Myelodysplastic Syndromes/Myeloproliferative Neoplasms: A Real-World Experience From a Developing Country
Awidi A, Alzu'bi M, Odeh N, Alrawabdeh J, Al Zyoud M, Hamadneh Y, Bawa'neh H, Magableh A, Alshorman A, Al-Fararjeh F, Aladily T, Zeidan A. Myelodysplastic Syndromes and Myelodysplastic Syndromes/Myeloproliferative Neoplasms: A Real-World Experience From a Developing Country. JCO Global Oncology 2024, 10: e2300281. PMID: 38422464, PMCID: PMC10914245, DOI: 10.1200/go.23.00281.Peer-Reviewed Original ResearchMeSH KeywordsDeveloping CountriesFemaleFerritinsHumansLeukemia, Myeloid, AcuteMaleMiddle AgedMyelodysplastic SyndromesRetrospective StudiesConceptsMyelodysplastic syndromeAML transformationMDS/myeloproliferative neoplasmRevised International Prognostic Scoring SystemClonal bone marrow disordersRisk of AML transformationInternational Prognostic Scoring SystemBaseline serum ferritin levelsMultivariate Cox regression modelMale to female ratioMyelodysplastic syndromes/myeloproliferative neoplasmsPrimary myelodysplastic syndromesPrognostic Scoring SystemSerum ferritin levelsMyelodysplastic syndrome subtypesBaseline serum ferritinBone marrow disordersLactate dehydrogenase levelsCox regression modelsJordan University HospitalRetrospective registry dataRisk of deathPeripheral cytopeniasBaseline ferritinIneffective hematopoiesisComparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Nanaa A, Atallah E, Shallis R, Guilherme S, Goldberg A, Saliba A, Patel A, Bewersdorf J, DuVall A, Bradshaw D, Abaza Y, Murthy G, Palmisiano N, Zeidan A, Kota V, Litzow M. Comparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood Cancer Journal 2024, 14: 32. PMID: 38378617, PMCID: PMC10879201, DOI: 10.1038/s41408-024-01000-2.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBridged Bicyclo Compounds, HeterocyclicHumansLeukemia, Myeloid, AcuteSulfonamidesTumor Suppressor Protein p53
2023
A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents
Bewersdorf J, Shallis R, Sharon E, Park S, Ramaswamy R, Roe C, Irish J, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents. Annals Of Hematology 2023, 103: 105-116. PMID: 38036712, DOI: 10.1007/s00277-023-05552-4.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsHistone Deacetylase InhibitorsHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesConceptsDose-limiting toxicityAcute myeloid leukemiaMarrow complete remissionPhase Ib trialAdverse eventsIb trialDose escalationNCI Cancer Therapy Evaluation ProgramAcute myeloid leukemia refractoryHematologic adverse eventsProtocol-defined responseDose level 1Anti-PD1 therapyAnti-PD1 antibodyDose-escalation designLimited clinical efficacySystems immunology approachHistone deacetylase inhibitor entinostatLeukemia refractoryMCR patientsComplete remissionRespiratory failureSuppressor cellsEscalation designClinical efficacyWhen 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 StatementsMeSH KeywordsClinical Decision-MakingHumansLeukemia, Myeloid, AcuteMutationMyelodysplastic SyndromesPrognosisConceptsInternational 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 revisionTargeting 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 pathwayTreatmentApoptosisStandardising acute myeloid leukaemia classification systems: a perspective from a panel of international experts
Shallis R, Daver N, Altman J, Komrokji R, Pollyea D, Badar T, Bewersdorf J, Bhatt V, de Botton S, de la Fuente Burguera A, Carraway H, Desai P, Dillon R, Duployez N, El Chaer F, Fathi A, Freeman S, Gojo I, Grunwald M, Jonas B, Konopleva M, Lin T, Mannis G, Mascarenhas J, Michaelis L, Mims A, Montesinos P, Pozdnyakova O, Pratz K, Schuh A, Sekeres M, Smith C, Stahl M, Subklewe M, Uy G, Voso M, Walter R, Wang E, Zeidner J, Žučenka A, Zeidan A. Standardising acute myeloid leukaemia classification systems: a perspective from a panel of international experts. The Lancet Haematology 2023, 10: e767-e776. PMID: 37572683, DOI: 10.1016/s2352-3026(23)00159-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid leukemiaClinical trial eligibilityInternational consensus classificationHeath care providersHealth care providersTrial eligibilityClassification systemResponse assessmentDisease definitionConsensus classificationPatientsDrug developmentLeukemiaConsistent management strategiesInternational expertsRegulatory pathwaysProvidersHematopathologistsCliniciansDiagnosisOral 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 StatementsMeSH KeywordsAzacitidineDecitabineHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesQuality of LifeConceptsAcute 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 malignanciesPhase 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 inhibitorsEpidemiology 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 StatementsMeSH KeywordsEpigenesis, GeneticHematopoiesisHumansLeukemia, Myeloid, AcuteMutationMyelodysplastic SyndromesConceptsMyelodysplastic 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 significancePathophysiologyEvolution 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 severityNovel Approaches and Future Directions in Myelodysplastic Syndrome Treatment
Bewersdorf J, Xie Z, Zeidan A. Novel Approaches and Future Directions in Myelodysplastic Syndrome Treatment. The Cancer Journal 2023, 29: 195-202. PMID: 37195776, DOI: 10.1097/ppo.0000000000000658.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk MDS patientsInternational Prognostic Scoring SystemPhase III clinical trialsErythropoiesis-stimulating agentsPrognostic scoring systemRisk stratification toolAdvanced clinical testingStandard of careAcute myeloid leukemiaTelomerase inhibitor imetelstatEncouraging early resultsMyelodysplastic Syndromes TreatmentAnemic patientsAgent monotherapyMDS patientsStratification toolSyndrome treatmentCombination therapyDysplastic changesClinical trialsMyeloid leukemiaTreatment decisionsClonal disorderTreatment selectionClinical testingImpact of Prophylactic Antibacterials on Coagulation Profiles and Bleeding in Patients with Acute Myeloid Leukemia/Myelodysplastic Syndrome
Allen C, Gautam S, Cheng W, Pine A, Podoltsev N, Zeidan A, Lee A, Shallis R. Impact of Prophylactic Antibacterials on Coagulation Profiles and Bleeding in Patients with Acute Myeloid Leukemia/Myelodysplastic Syndrome. Acta Haematologica 2023, 146: 287-292. PMID: 37166332, DOI: 10.1159/000530153.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesRetrospective StudiesConceptsAML/myelodysplastic syndromeAcute myeloid leukemiaInternational normalized ratioAntibacterial prophylaxisMyelodysplastic syndromeProphylactic antibacterialsCoagulation profileAcute myeloid leukemia/myelodysplastic syndromeDiagnosis of AMLHigher international normalized ratioLeukemia/myelodysplastic syndromePartial thromboplastin time prolongationYale-New Haven HospitalYale-New HavenRetrospective cohort studyAbnormal coagulation profileGroup of patientsTime of admissionHigh rateIndividual patient encountersInstitutional review boardAntibacterial exposureRelevant bleedingAdult patientsCohort studyCost-Effectiveness Analyses in AML: What Have We Learned, How Should This Impact Patient Care, and What Needs to Be Done in the Future?
Bewersdorf J, Huntington S, Zeidan A. Cost-Effectiveness Analyses in AML: What Have We Learned, How Should This Impact Patient Care, and What Needs to Be Done in the Future? Journal Of The National Comprehensive Cancer Network 2023, 21: 522-528. PMID: 37037494, DOI: 10.6004/jnccn.2023.70012.Peer-Reviewed Original ResearchMeSH KeywordsAdultCost-Benefit AnalysisCost-Effectiveness AnalysisHumansLeukemia, Myeloid, AcutePatient CareUnited StatesConceptsCost-effectiveness analysisEconomic modeling techniquesCost-effectiveness studiesFinite financial resourcesDrug pricesHealth policy decisionsPolicy decisionsFinancial resourcesResource allocationUnited StatesPublic interestCostHealthcare systemPricesSuch analysesLimited resourcesAllocationCountriesConsumersData sourcesPayersAssumptionBenefitsBudgetary considerationsDifferent interventionsSecond malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea
Wang R, Shallis R, Stempel JM, Huntington SF, Zeidan AM, Gore SD, Ma X, Podoltsev NA. Second malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea. Blood Advances 2023, 7: 734-743. PMID: 35917456, PMCID: PMC9989521, DOI: 10.1182/bloodadvances.2022008259.Peer-Reviewed Original ResearchConceptsSecond malignanciesAcute myeloid leukemiaOlder patientsMyelodysplastic syndromeMyeloproliferative neoplasmsHU usersHigh riskPolycythemia veraEssential thrombocythemiaRisk of SMAML/myelodysplastic syndromeClassical Philadelphia chromosome-negative myeloproliferative neoplasmsImpact of hydroxyureaRetrospective cohort studyUse of hydroxyureaPhiladelphia chromosome-negative myeloproliferative neoplasmsClassical myeloproliferative neoplasmsCumulative incidence probabilityCohort studyCytoreductive therapyPatient characteristicsMedian ageHU useMyeloid leukemiaSecondary myelofibrosisSTIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2
Zeidan A, Giagounidis A, Sekeres M, Xiao Z, Sanz G, Van Hoef M, Ma F, Hertle S, Santini V. STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Future Oncology 2023, 19: 631-642. PMID: 37083373, DOI: 10.2217/fon-2022-1237.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntimetabolites, AntineoplasticAzacitidineClinical Trials, Phase III as TopicHumansLeukemia, Myeloid, AcuteLeukemia, Myelomonocytic, ChronicMyelodysplastic SyndromesConceptsHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaMyelodysplastic syndromeCMML-2Tim-3Hematopoietic stem cell transplantationT-cell immunoglobulin domainMucin domain 3Risk myelodysplastic syndromesPhase III trialsStem cell transplantationLeukemic stem cellsFavorable tolerabilityIII trialsNovel immunotherapiesPoor outcomeCell transplantationLeukemic blastsClinical trialsNovel therapiesMyelomonocytic leukemiaDurable benefitImmune systemMyeloid malignanciesMeaningful improvementsHow 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 updatesTreatmentVenetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States
Zeidan A, Pollyea D, Borate U, Vasconcelos A, Potluri R, Rotter D, Kiendrebeogo Z, Gaugler L, Prebet T, Strocchia M, Bonifacio G, Chen C. Venetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States. Annals Of Hematology 2023, 102: 749-754. PMID: 36732419, PMCID: PMC10285011, DOI: 10.1007/s00277-023-05109-5.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantAcute myeloid leukemiaRelapse-free survivalIntensive chemotherapyComplete remissionOverall survivalMyeloid leukemiaRetrospective analysisMedian relapse-free survivalElectronic medical record databaseFlatiron Health databaseMedian overall survivalStem cell transplantMedical record databaseElectronic health recordsHSCT ratesRelapse rateCell transplantControlled TrialsTreatment outcomesHealth databasesPatientsRecord databaseMonthsHealth recordsAn 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 mutationsRelapseAdvances in myelodysplastic syndromes: promising novel agents and combination strategies
Madanat Y, Xie Z, Zeidan A. Advances in myelodysplastic syndromes: promising novel agents and combination strategies. Expert Review Of Hematology 2023, 16: 51-63. PMID: 36620919, DOI: 10.1080/17474086.2023.2166923.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeMultiple novel agentsMyelodysplastic syndromeNovel agentsClinical trialsTreatment optionsPhase III clinical trialsSelect clinical trialsLow-risk diseaseClonal hematopoietic stem cell neoplasmHigh-risk diseaseBest treatment optionHematopoietic stem cell neoplasmsInnate immune systemStem cell neoplasmMechanism of actionHMA therapyEarly safetyTreatment paradigmEfficacy dataCell neoplasmsDrug combinationsClinical developmentUnmet needImmune system
2022
Cost-effectiveness of azacitidine and ivosidenib in newly diagnosed older, intensive chemotherapy-ineligible patients with IDH1-mutant acute myeloid leukemia
Bewersdorf J, Patel K, Goshua G, Shallis R, Podoltsev N, Stahl M, Stein E, Huntington S, Zeidan A. Cost-effectiveness of azacitidine and ivosidenib in newly diagnosed older, intensive chemotherapy-ineligible patients with IDH1-mutant acute myeloid leukemia. Leukemia & Lymphoma 2022, 64: 454-461. PMID: 36493798, PMCID: PMC9957935, DOI: 10.1080/10428194.2022.2140288.Peer-Reviewed Original ResearchMeSH KeywordsAzacitidineCost-Benefit AnalysisHumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcutePyridinesQuality-Adjusted Life YearsUnited States