2024
A Niche Driven Mechanism Determines Response to ATRA and a Mutation-Independent Therapeutic Approach for MDS and AML
Mosialou I, Ali A, Cuesta-Dominguez A, Labella R, Vgenopoulou V, Bisikirska B, Galan-Diez M, Wang A, Bewersdorf J, Liang C, Heiblig M, Jurcic J, Berman E, Rabadan R, Kornblau S, Garcia-Manero G, Raza A, Kousteni S. A Niche Driven Mechanism Determines Response to ATRA and a Mutation-Independent Therapeutic Approach for MDS and AML. Blood 2024, 144: 5788-5788. DOI: 10.1182/blood-2024-212307.Peer-Reviewed Original ResearchAcute myeloid leukemiaAcute myeloid leukemia patientsStandard of careComplete responseMyelodysplastic syndrome patientsMyelodysplastic syndromeOverall response rateResponse to ATRAAll-trans-retinoic acidB-cateninOsteoblast lineage cellsMyeloid malignanciesTreatment responseLineage cellsDuration of follow-upMonitoring of treatment responseResponse rateBone marrow biopsyAbsolute neutrophil countAdverse risk groupAcute myeloid leukemia cellsNotch signalingAssociated with complete inhibitionResponse to all-trans-retinoic acidResistance to standardImmune Landscape and Outcomes of Patients with RNA Splicing Factor-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes Treated with Azacitidine +/- the Anti-PD-L1 Antibody Durvalumab
Bewersdorf J, Hasle V, Shallis R, Thompson E, De Menezes D, Rose S, Boss I, Mendez L, Podoltsev N, Stahl M, Kewan T, Halene S, Haferlach T, Fox B, Zeidan A. Immune Landscape and Outcomes of Patients with RNA Splicing Factor-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes Treated with Azacitidine +/- the Anti-PD-L1 Antibody Durvalumab. Blood 2024, 144: 4585. DOI: 10.1182/blood-2024-194929.Peer-Reviewed Original ResearchAcute myeloid leukemiaAnti-PD-L1 antibody durvalumabOverall response rateMyelodysplastic syndromeComplete responseBM aspiratesMyeloid leukemiaInternational Working GroupBone marrowMyelodysplastic syndromes treated with azacitidineAcute myeloid leukemia ptsWild-type acute myeloid leukemiaSecondary acute myeloid leukemiaResponse criteriaAnti-PD-L1Immune checkpoint inhibitorsTreated with azacitidineOutcomes of patientsAny-cause deathGeneration of neoantigensVariant allele frequencySusceptible to treatmentMarrow CRAdverse cytogeneticsCheckpoint inhibitorsThe Prognostic and Predictive Value of RUNX1 Mutations in Newly Diagnosed Acute Myeloid Leukemia - an International Multicenter Cohort Study
Bystrom R, Bewersdorf J, Liu Y, Schaefer E, Shallis R, Boussi L, Zucenka A, Garciaz S, Aguirre L, DeAngelo D, Stone R, Luskin M, Garcia J, Winer E, Chen E, Wadleigh M, Ling K, Stein E, Goldberg A, Zeidan A, Shimony S, Stahl M. The Prognostic and Predictive Value of RUNX1 Mutations in Newly Diagnosed Acute Myeloid Leukemia - an International Multicenter Cohort Study. Blood 2024, 144: 2947-2947. DOI: 10.1182/blood-2024-205581.Peer-Reviewed Original ResearchAcute myeloid leukemiaComposite complete responseMedian OSRUNX1 mutationsComplete responseIntensive chemotherapyOverall survivalMyelodysplastic syndromeAllo-SCTIntermediate riskPredictive valueMyeloid leukemiaInternational multicenter retrospective cohort studyTreatment strategiesCohort studyNewly diagnosed acute myeloid leukemiaAllogeneic stem cell transplantationMulticenter retrospective cohort studyNext-generation sequencingAntecedent MDSConcomitant TP53 mutationIncomplete count recoveryTreated with ICStem cell transplantationAdverse risk featuresImpact of Response to Hypomethylating Agent-Based Therapy on Survival Outcomes in the Context of Baseline Clinical-Molecular Risk and Transplant Status in Patients with Myelodysplastic Syndromes/Neoplasms (MDS): An Analysis from the International Consortium for MDS (icMDS) Validate Database
Rolles B, Bewersdorf J, Kewan T, Blaha O, Stempel J, Lanino L, Al Ali N, DeZern A, Sekeres M, Uy G, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, McMahon C, Shallis R, Zeidner J, Savona M, Frumm S, Barua S, Chandhok N, Logothetis C, Bidikian A, Getz T, Roboz G, Wang E, Harris A, Amaya M, Hawkins H, Ball S, Grenet J, Xie Z, Madanat Y, Abaza Y, Badar T, Haferlach T, Maciejewski J, Sallman D, Enjeti A, Al-Rabi K, Halahleh K, Hiwase D, Diez-Campelo M, Valcarcel D, Haferlach C, Pleyer L, Kotsianidis I, Pappa V, Santini V, Consagra A, Al-Kali A, Ogawa S, Nannya Y, Della Porta M, Komrokji R, Zeidan A, Stahl M. Impact of Response to Hypomethylating Agent-Based Therapy on Survival Outcomes in the Context of Baseline Clinical-Molecular Risk and Transplant Status in Patients with Myelodysplastic Syndromes/Neoplasms (MDS): An Analysis from the International Consortium for MDS (icMDS) Validate Database. Blood 2024, 144: 664-664. DOI: 10.1182/blood-2024-208034.Peer-Reviewed Original ResearchComposite complete responseAllo-HCTOverall survivalComplete responseIPSS-MHMA therapyMedian OSResponse criteriaAllogeneic stem cell transplantationPartial hematologic recoveryClinical response criteriaStem cell transplantationHypomethylating agent-based therapyAgent-based therapyClinical practiceCox regression analysisResponse to treatmentAvailability of donorsDecitabine monotherapyImpact OSOS benefitHematologic recoveryAzacitidine monotherapyCell transplantationCombination therapy
2023
Clinical Implications of TP53 Mutations/Allelic State in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Treated with Hypomethylating Agents (HMA)- a Multicenter, Retrospective Analysis from the Validate Database
Kewan T, Bewersdorf J, Blaha O, Stahl M, Al Ali N, DeZern A, Sekeres M, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, Amaya M, Zeidner J, Savona M, Stempel J, Chandhok N, Cochran H, Ramaswamy R, Singh A, Roboz G, Rolles B, Wang E, Harris A, Shallis R, Xie Z, Padron E, Maciejewski J, Della Porta M, Komrokji R, Sallman D, Zeidan A. Clinical Implications of TP53 Mutations/Allelic State in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Treated with Hypomethylating Agents (HMA)- a Multicenter, Retrospective Analysis from the Validate Database. Blood 2023, 142: 1002. DOI: 10.1182/blood-2023-186875.Peer-Reviewed Original ResearchOverall response rateMedian overall survivalOverall survivalComplete responseHMA initiationHMA therapyMultivariable Cox proportional hazards regression modelsCox proportional hazards regression modelHigh-risk disease featuresComplex karyotypeProportional hazards regression modelsWorse overall survivalLog-rank testHazards regression modelsSignificant differencesLogistic regression modelsAllogenic HSCTBM biopsyHMA cyclesMDS-EBTherapy initiationMedian ageRegression modelsCR ratePoor outcomeIntensive Induction Chemotherapy (IC) Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in IDH1- or IDH2-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study
Bewersdorf J, Shimony S, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Intensive Induction Chemotherapy (IC) Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in IDH1- or IDH2-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study. Blood 2023, 142: 1589. DOI: 10.1182/blood-2023-174283.Peer-Reviewed Original ResearchIntensive induction chemotherapyAcute myeloid leukemiaComposite complete responseMedian overall survivalOverall survivalComplete responseIDH2 mutationsAllo-SCTLarge multicenter retrospective cohort studyMulticenter retrospective cohort studyAllogeneic stem cell transplantationSecondary acute myeloid leukemiaComparable overall survivalIDH1 inhibitor ivosidenibHigh rateRetrospective cohort studyStem cell transplantationLog-rank testStandard of careLarge academic centerYears of ageEffect of treatmentIDH-mutant AMLMultivariable stepwiseFit patientsWhat Is the Optimal Treatment Modality in Molecularly Defined Secondary AML? a Multicenter Cohort Study
Shimony S, Bewersdorf J, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Chen E, Ramos J, Lindsley R, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. What Is the Optimal Treatment Modality in Molecularly Defined Secondary AML? a Multicenter Cohort Study. Blood 2023, 142: 1478. DOI: 10.1182/blood-2023-172763.Peer-Reviewed Original ResearchAcute myeloid leukemiaComposite complete responseStem cell transplantationOverall survivalCPX-351Complete responseTreatment modalitiesMonosomal karyotypeCohort studyOdds ratioTreatment groupsLarge multicenter retrospective cohort studyMulticenter retrospective cohort studyAllogeneic stem cell transplantationSecondary acute myeloid leukemiaIncomplete count recoveryImproved overall survivalMedian overall survivalMulticenter cohort studyRetrospective cohort studyWorse overall survivalOptimal treatment modalityOptimal treatment selectionLog-rank testEffect of treatmentIntensive Induction Chemotherapy Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in NPM1-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study
Bewersdorf J, Shimony S, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Intensive Induction Chemotherapy Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in NPM1-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study. Blood 2023, 142: 2964. DOI: 10.1182/blood-2023-174285.Peer-Reviewed Original ResearchNPM1 mutant acute myeloid leukemiaIntensive induction chemotherapyAcute myeloid leukemiaComposite complete responseMedian overall survivalOverall survivalComplete responseAllo-SCTPt ageAbnormal cytogeneticsCohort studyMyelodysplastic syndromePolymerase chain reactionClinical trialsMyeloid leukemiaNPM1 mutationsLarge multicenter retrospective cohort studyTime-varying covariatesMulticenter retrospective cohort studyAllogeneic stem cell transplantationPrior myelodysplastic syndromeMulticenter cohort studyRetrospective cohort studyStem cell transplantationPrior chemotherapy exposure
2021
Management of patients with higher-risk myelodysplastic syndromes after failure of hypomethylating agents: What is on the horizon?
Bewersdorf JP, Zeidan AM. Management of patients with higher-risk myelodysplastic syndromes after failure of hypomethylating agents: What is on the horizon? Best Practice & Research Clinical Haematology 2021, 34: 101245. PMID: 33762100, DOI: 10.1016/j.beha.2021.101245.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHigh-risk myelodysplastic syndromeHMA failureMyelodysplastic syndromeAgent azacitidineSalvage therapyNovel immune checkpoint inhibitorsEffective salvage therapyBCL-2 inhibitor venetoclaxCommon clinical dilemmaManagement of patientsStandard of careRationale drug developmentCheckpoint inhibitorsFrontline therapyMost patientsComplete responseMDS patientsFrontline settingFrontline treatmentShorter survivalClinical dilemmaInhibitor venetoclaxClinical testingPatients
2020
Management of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole?
Bewersdorf JP, Zeidan AM. Management of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole? Expert Review Of Hematology 2020, 13: 1131-1142. PMID: 32876498, DOI: 10.1080/17474086.2020.1819233.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiomarkersCombined Modality TherapyDisease ManagementDisease SusceptibilityDNA MethylationDrug DevelopmentDrug Resistance, NeoplasmHumansMolecular Targeted TherapyMutationMyelodysplastic SyndromesPrognosisRemission InductionRetreatmentTreatment FailureTreatment OutcomeConceptsHigh-risk myelodysplastic syndromeHMA failureMyelodysplastic syndromeHR-MDS patientsRisk myelodysplastic syndromesMainstay of treatmentImmune pathogenesisMost patientsComplete responseImmune therapyAbysmal prognosisNovel agentsTherapeutic approachesTherapeutic conceptsImmune evasionTreatment approachesPatientsGenetic testingSyndromePathogenesisTreatmentMolecular mechanismsRecent studiesFailureAnnual MeetingInterferon alpha therapy in essential thrombocythemia and polycythemia vera—a systematic review and meta-analysis
Bewersdorf JP, Giri S, Wang R, Podoltsev N, Williams RT, Tallman MS, Rampal RK, Zeidan AM, Stahl M. Interferon alpha therapy in essential thrombocythemia and polycythemia vera—a systematic review and meta-analysis. Leukemia 2020, 35: 1643-1660. PMID: 32868875, PMCID: PMC7917159, DOI: 10.1038/s41375-020-01020-4.Peer-Reviewed Original ResearchConceptsOverall response ratePEG-IFNPolycythemia veraEssential thrombocythemiaHematologic responsePV patientsResponse rateSystematic reviewMeta-regression analysis resultsSafe long-term treatmentPartial hematologic responseSafety of interferonInterferon-alpha therapyLong-term treatmentRandom-effects modelMeta-regression analysisWeb of ScienceTreatment discontinuationCochrane RegistryAdverse eventsComplete responsePartial responsePrimary outcomeThromboembolic complicationsClinical trialsInterferon Therapy in Myelofibrosis: Systematic Review and Meta-analysis
Bewersdorf JP, Giri S, Wang R, Podoltsev N, Williams RT, Rampal RK, Tallman MS, Zeidan AM, Stahl M. Interferon Therapy in Myelofibrosis: Systematic Review and Meta-analysis. Clinical Lymphoma Myeloma & Leukemia 2020, 20: e712-e723. PMID: 32669244, PMCID: PMC7541411, DOI: 10.1016/j.clml.2020.05.018.Peer-Reviewed Original ResearchConceptsOverall response rateTreatment of myelofibrosisPEG-IFNMF patientsResponse rateHematologic responseSystematic reviewFormulations of interferonPartial hematologic responseCochrane Central RegisterComplete hematologic responseRisk of progressionRole of interferonAcute myeloid leukemiaPhiladelphia chromosome-negative myeloproliferative neoplasmsRandom-effects modelBone marrow failureWeb of ScienceTreatment discontinuationCentral RegisterConstitutional symptomsHematologic improvementInterferon therapyAdverse eventsComplete response