2024
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
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 inhibitorsCost-Effectiveness of Allogeneic Hematopoietic Stem Cell Transplantation Versus Consolidation Chemotherapy for Patients with Intermediate Risk Acute Myeloid Leukemia
Alhajahjeh A, Patel K, Shallis R, Podoltsev N, Kewan T, Stempel J, Mendez L, Huntington S, Stahl M, Zeidan A, Goshua G, Bewersdorf J. Cost-Effectiveness of Allogeneic Hematopoietic Stem Cell Transplantation Versus Consolidation Chemotherapy for Patients with Intermediate Risk Acute Myeloid Leukemia. Blood 2024, 144: 788. DOI: 10.1182/blood-2024-201535.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationUpfront hematopoietic stem cell transplantationDisease-free survivalAcute myeloid leukemiaIntermediate risk acute myeloid leukemiaConsolidation chemotherapyCurative therapeutic modalityOverall survivalOne-way sensitivity analysesEuropean LeukemiaNetIncremental net monetary benefitMyeloid leukemiaMortality associated with hematopoietic stem cell transplantationCost-effective strategyTherapeutic modalitiesFavorable risk AMLSalvage hematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationCycles of consolidation chemotherapyUS health system perspectiveDiagnosed AMLFollow-up of patientsSurvival analysisHigh-dose cytarabineLines of therapyToxicity and Efficacy of Isavuconazole Vs Voriconazole As Anti-Fungal Prophylaxis for Patients with Acute Myeloid Leukemia
Hunter C, Bewersdorf J, Mendez L, Podoltsev N, Zeidan A, Eighmy W, Roeder H, Malinis M, Shallis R. Toxicity and Efficacy of Isavuconazole Vs Voriconazole As Anti-Fungal Prophylaxis for Patients with Acute Myeloid Leukemia. Blood 2024, 144: 1480-1480. DOI: 10.1182/blood-2024-211250.Peer-Reviewed Original ResearchInvasive fungal infectionsAcute myeloid leukemiaAntifungal prophylaxisDiagnosed AMLDrug-drug interactionsTransaminase elevationVisual disturbancesRates of invasive fungal infectionsInvasive fungal infections incidenceBaseline ANCCD4 countMyeloid leukemiaAllogeneic stem cell transplantationAnti-fungal prophylaxisAcute myeloid leukemia diagnosisDuration of neutropeniaBaseline CD4 countLess-intensive therapyStem cell transplantationPatient baseline characteristicsSide effect profileCandida sppTriazole agentsWilcoxon rank sum testAntifungal voriconazoleRisk Factors and Predictors of Outcomes after Invasive Fungal Infection Among Patients with Acute Myeloid Leukemia
Hunter C, Bewersdorf J, Mendez L, Podoltsev N, Zeidan A, Eighmy W, Roeder H, Malinis M, Shallis R. Risk Factors and Predictors of Outcomes after Invasive Fungal Infection Among Patients with Acute Myeloid Leukemia. Blood 2024, 144: 4253. DOI: 10.1182/blood-2024-211426.Peer-Reviewed Original ResearchInvasive fungal infection diagnosisInvasive fungal infectionsAcute myeloid leukemiaInvasive Fungal Infection GroupAntifungal prophylaxis agentAntifungal prophylaxisCases of invasive fungal infectionsRates of invasive fungal infectionsFungal infectionsMyeloid leukemiaPrevent invasive fungal infectionsMycoses Study Group Education and Research ConsortiumRate of mortalityIFI patientsAllogeneic stem cell transplantationRisk factorsConsensus definitionAssociated with early mortalityNon-IFI groupSingle-gene mutationsPeriod of neutropeniaDays of neutropeniaAcute myeloid leukemia subtypesStem cell transplantationKaplan-Meier methodThe 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 featuresLeukemia Physician's Perspective on Transplant in Patients with TP53 Mutated Acute Myeloid Leukemia
Moreno Vanegas Y, El Khatib S, Hisrich B, Coltoff A, Shallis R, Patel A, Bewersdorf J, Oh T, Abaza Y, Foucar C, Goldberg A, Duvall A, Atallah E, Litzow M, Badar T. Leukemia Physician's Perspective on Transplant in Patients with TP53 Mutated Acute Myeloid Leukemia. Blood 2024, 144: 1487-1487. DOI: 10.1182/blood-2024-205782.Peer-Reviewed Original ResearchAcute myeloid leukemiaTP53-mAllo-HCTComplex cytogeneticsHypomethylating agentsInternational Consensus ClassificationRefractory diseaseSecondary AMLOverall survivalMyeloid leukemiaTP53-mutated acute myeloid leukemiaDe novo acute myeloid leukemiaProgressive acute myeloid leukemiaSecondary acute myeloid leukemiaAllogeneic hematopoietic cell transplantationMedian overall survivalTP53 allelic stateIncomplete count recoveryLow-intensity regimensReviewed electronic medical recordsHematopoietic cell transplantationRate of relapseMulticenter observational studyOverall response ratePatient selection criteriaVenetoclax-Based Therapy Versus Intensive Chemotherapy Followed By Allogeneic-Stem Cell Transplantation for High-Risk Elderly Acute Myeloid Leukemia
Iat A, Bewersdorf J, Gilhodes J, Liu Y, Shallis R, Boussi L, Zucenka A, Bystrom R, DeAngelo D, Berton G, Soua A, Ling K, Aguirre L, Stone R, Luskin M, Garcia J, Winer E, Chen E, Wadleigh M, Goldberg A, Zeidan A, Cluzeau T, Shimony S, Stahl M, Garciaz S. Venetoclax-Based Therapy Versus Intensive Chemotherapy Followed By Allogeneic-Stem Cell Transplantation for High-Risk Elderly Acute Myeloid Leukemia. Blood 2024, 144: 1508. DOI: 10.1182/blood-2024-207045.Peer-Reviewed Original ResearchCumulative incidence of relapseRelapse-free survivalAcute myeloid leukemiaOverall response rateAdverse risk cytogeneticsAllo-SCTVEN-based therapyNon-relapse mortalityIntensive chemotherapyComposite CROverall survivalIC groupMedian OSMyeloid leukemiaElderly patientsTherapy-related acute myeloid leukemiaHigh-risk acute myeloid leukemiaAllogeneic stem-cell transplantationMedian time to relapseElderly acute myeloid leukemiaLong-term disease controlResponse rateFrequent cytogenetic alterationsProspective validation trialVIALE-A trialFuture directions in myelodysplastic syndromes/neoplasms and acute myeloid leukaemia classification: from blast counts to biology
Della Porta M, Bewersdorf J, Wang Y, Hasserjian R. Future directions in myelodysplastic syndromes/neoplasms and acute myeloid leukaemia classification: from blast counts to biology. Histopathology 2024 PMID: 39450427, DOI: 10.1111/his.15353.Peer-Reviewed Original ResearchAcute myeloid leukemiaIntegration of genomic dataGenomic informationGenomic dataPresence of SF3B1 mutationsDisease entityMethylation profilesAML classificationRecurrent genetic abnormalitiesHaematopoietic cell proliferationPercentage of myeloblastsGene expressionGenetic featuresMultiple diagnostic modalitiesPatient risk stratificationSF3B1 mutationsBlast countDisease pathogenesisGenetic abnormalitiesCell proliferationTP53 abnormalitiesDiagnostic modalitiesMyeloid leukemiaBone marrowPatient cohortIntensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML
Bewersdorf J, Shimony S, Shallis R, Liu Y, Berton G, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Bystrom R, Lindsley R, Chen E, Perez J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML. Blood Advances 2024, 8: 4845-4855. PMID: 38941537, PMCID: PMC11416634, DOI: 10.1182/bloodadvances.2024012858.Peer-Reviewed Original ResearchIntensive induction chemotherapyAcute myeloid leukemiaNPM1-Mutant Acute Myeloid LeukemiaInduction chemotherapyHypomethylating agentsMulticenter retrospective cohort study of patientsPatients treated with ICAllogeneic stem cell transplantationRetrospective cohort study of patientsMulticenter retrospective cohort studyCohort study of patientsComposite complete remissionStem cell transplantationYears-oldFLT3-ITD mutationStudy of patientsStandard of careNormal cytogeneticsComplete remissionCell transplantationNPM1 mutationsMyeloid leukemiaFLT3-ITDYounger patientsOlder patientsAcute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome
Alhajahjeh A, Bewersdorf J, Bystrom R, Zeidan A, Shimony S, Stahl M. Acute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome. Leukemia & Lymphoma 2024, 65: 1541-1551. PMID: 38962996, DOI: 10.1080/10428194.2024.2367040.Peer-Reviewed Original ResearchAcute myeloid leukemiaIntensive chemotherapyHypomethylating agentsMyeloid leukemiaAllogeneic stem cell transplantationAcute myeloid leukemia casesAcute myeloid leukemia subtypesStem cell transplantationComplex hematological malignancyCurrent treatment modalitiesRare genetic anomalyCell transplantationHematologic malignanciesTreatment modalitiesClinical outcomesTreatment responseInv(3Genetic alterationsLeukemia developmentTreatment strategiesCellular processesGenetic anomaliesLeukemiaFusion geneClinical implicationsPrognostic impact of ‘multi-hit’ versus ‘single-hit’ TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases
Badar T, Nanaa A, Atallah E, Shallis R, Craver E, Li Z, Goldberg A, Saliba A, Patel A, Bewersdorf J, Duvall A, Burkart M, Bradshaw D, Abaza Y, Stahl M, Palmisiano N, Murthy S, Zeidan A, Kota V, Patnaik M, Litzow M. Prognostic impact of ‘multi-hit’ versus ‘single-hit’ TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases. Haematologica 2024, 109: 3533-3542. PMID: 38813716, PMCID: PMC11532685, DOI: 10.3324/haematol.2024.285000.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyelodysplastic syndromeComplex cytogeneticsMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationLower-risk myelodysplastic syndromesHematopoietic stem cell transplantationHigher-risk myelodysplastic syndromesOutcomes of SHStem cell transplantationAllo-HCTTP53 alterationsPrognostic impactMyeloid malignanciesTP53 mutationsCell transplantationFLT3-ITDIDH1 mutationMultivariate analysisSupportive careUS academic institutionsNeoplastic diseasePatientsSuperior EFSPredicting outcomeCost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia
Bewersdorf J, Patel K, Shallis R, Podoltsev N, Kewan T, Stempel J, Mendez L, Stahl M, Stein E, Huntington S, Goshua G, Zeidan A. Cost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia. Leukemia & Lymphoma 2024, 65: 1136-1144. PMID: 38648559, PMCID: PMC11265977, DOI: 10.1080/10428194.2024.2344052.Peer-Reviewed Original ResearchQuality-adjusted life yearsCompletion of consolidation therapyFLT3-mutant acute myeloid leukemiaAllogeneic hematopoietic cell transplantationIncremental cost-effectiveness ratioProbabilistic sensitivity analysesImproved overall survivalHematopoietic cell transplantationPartitioned survival analysis modelAcute myeloid leukemiaCost-effectiveness ratioFLT3 inhibitor quizartinibHealth economic implicationsConsolidation therapyInduction chemotherapyAverage wholesale priceOverall survivalCell transplantationContinuous therapyMyeloid leukemiaITD mutationQuizartinibIncremental costCost-effective optionLife yearsComparing 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 Research
2023
Moving toward disease modification in polycythemia vera
Bewersdorf J, How J, Masarova L, Bose P, Pemmaraju N, Mascarenhas J, Rampal R. Moving toward disease modification in polycythemia vera. Blood 2023, 142: 1859-1870. PMID: 37729609, DOI: 10.1182/blood.2023021503.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaProgression to myelofibrosisPolycythemia veraCytoreductive therapyBCR-ABL1-negative myeloproliferative neoplasmsLow-risk PVLow-risk diseaseHistory of thrombosisHigh-risk diseaseDisease-modifying treatment modalitiesAssociated with higher ratesEvolving treatment landscapeClinically meaningful outcome measuresDisease-related symptomsInterferon alfaMyeloproliferative neoplasmsThromboembolic eventsPatient ageMyeloid leukemiaTreatment modalitiesIFN-a2bTherapeutic phlebotomyActivating mutationsVasomotor symptomsDisease courseIntensive 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 exposureComparable Survival of Treatment Naïve TP53 Mutated Acute Myeloid Leukemia Treated with Hypomethylating Agent Compared to Hypomethylating Agent Plus Venetoclax Based Therapy
Badar T, Atallah E, Shallis R, Patel A, De Camargo Correia G, Goldberg A, Saliba A, Bewersdorf J, Duvall A, Bradshaw D, Abaza Y, Murthy S, Palmisiano N, Kota V, Litzow M. Comparable Survival of Treatment Naïve TP53 Mutated Acute Myeloid Leukemia Treated with Hypomethylating Agent Compared to Hypomethylating Agent Plus Venetoclax Based Therapy. Blood 2023, 142: 592. DOI: 10.1182/blood-2023-184626.Peer-Reviewed Original ResearchAcute myeloid leukemiaComplete remission rateOverall survivalDuration of responseMultivariable analysisComplex cytogeneticsAllo-HCTRemission rateMyeloid leukemiaAllogeneic stem cell transplantSecondary acute myeloid leukemiaAdverse-risk diseaseCR/CRiMedian overall survivalOutcome of ptsResults Baseline characteristicsKaplan-Meier methodMore effective treatment strategiesSignificant univariate predictorsStem cell transplantEffective treatment strategiesReal-world studyLogistic regression modelsMedian followVEN groupTP53 Y220C Mutations in Patients with Myeloid Malignancies
Gener-Ricos G, Bewersdorf J, Loghavi S, Goldberg A, Famulare C, Issa G, Borthakur G, Kadia T, Carter B, Patel K, Andreeff M, Stein E, DiNardo C. TP53 Y220C Mutations in Patients with Myeloid Malignancies. Blood 2023, 142: 1477. DOI: 10.1182/blood-2023-189343.Peer-Reviewed Original ResearchLeukemia-free survivalAcute myeloid leukemiaMedian leukemia-free survivalVariant allele frequencyMedian follow-upStem cell transplantationMyeloid neoplasmsHot spot mutationsTP53 mutationsCo-mutationsFollow-upMyelodysplastic syndromeMyeloid malignanciesOverall survivalHematologic malignanciesMyeloid leukemiaSolid tumorsTransformation to acute myeloid leukemiaMedian variant allele frequencyTherapy-related myeloid neoplasmsAcute myeloid leukemia transformationMemorial Sloan-Kettering Cancer CenterY220C mutationTP53 co-mutationsNext generation sequencing assayWhen 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 revisionManagement of Acute Myeloid Leukemia with Myelodysplasia-Related Changes and Therapy-Related Acute Myeloid Leukemia
Bewersdorf J, Zeidan A. Management of Acute Myeloid Leukemia with Myelodysplasia-Related Changes and Therapy-Related Acute Myeloid Leukemia. 2023, 119-128. DOI: 10.1007/978-981-99-3810-0_8.ChaptersTherapy-related AMLAcute myeloid leukemiaSecondary AMLAML-MRCMyeloid leukemiaRandomized phase III clinical trialsPhase III clinical trialsAdverse cytogenetic featuresOverall survival benefitDe novo AMLT-AML patientsYears of ageHigh-risk mutationsInduction chemotherapyMonosomal karyotypeCPX-351Intensive chemotherapyNovo AMLSurvival benefitTreatment landscapeAdverse prognosisFrontline treatmentSubgroup analysisClinical trialsConventional chemotherapyTargeting 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 pathwayTreatmentApoptosis