2024
Future 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 cohortAnalyzing determinants of premature trial discontinuation in leukemia clinical trials
Rotter L, Alhajahjeh A, Stempel J, Grimshaw A, Bewersdorf J, Blaha O, Kewan T, Podoltsev N, Shallis R, Mendez L, Stahl M, Zeidan A. Analyzing determinants of premature trial discontinuation in leukemia clinical trials. Leukemia & Lymphoma 2024, ahead-of-print: 1-9. PMID: 39440622, DOI: 10.1080/10428194.2024.2416565.Peer-Reviewed Original ResearchClinical trialsSlow accrualLeukemia trialsEarly-phase trialsNon-randomized trialsAcademic-sponsored trialsImprove patient outcomesLeukemia clinical trialsSingle-centerTrial discontinuationSponsored trialsSmall trialsLeukemiaEarly terminationPatient outcomesLate-phaseIndependent reviewersTermination ratesComprehensive searchTrialsTargeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions
Bidikian A, Bewersdorf J, Shallis R, Getz T, Stempel J, Kewan T, Stahl M, Zeidan A. Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions. Expert Review Of Anticancer Therapy 2024, 24: 1131-1146. PMID: 39367718, DOI: 10.1080/14737140.2024.2414071.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsTargeted therapyLR-MDSHR-MDSHypoxia-inducible factorAllogeneic hematopoietic stem cell transplantationLandscape of targeted therapiesHematopoietic stem cell transplantationHeterogeneous group of hematologic malignanciesGroup of hematologic malignanciesMolecular prognostic toolsDuration of responseStem cell transplantationTrial designClinical trial designHypomethylating agentsCell transplantationHematologic malignanciesImprove patient outcomesRNA splicing machineryImmune evasionPrognostic toolTGF-betaTherapyEffective treatmentPacritinib Response Is Associated With Overall Survival in Myelofibrosis: PERSIST‐2 Landmark Analysis of Survival
Ajufo H, Bewersdorf J, Harrison C, Palandri F, Mascarenhas J, Palmer J, Gerds A, Kiladjian J, Buckley S, Derkach A, Roman‐Torres K, Rampal R. Pacritinib Response Is Associated With Overall Survival in Myelofibrosis: PERSIST‐2 Landmark Analysis of Survival. European Journal Of Haematology 2024 PMID: 39400386, DOI: 10.1111/ejh.14321.Peer-Reviewed Original ResearchSpleen volume reductionOverall survivalOS benefitNon-respondersAssociated with improved OSPatients treated with ruxolitinibAssociated with overall survivalAssociated with significant OS benefitImproved overall survivalSignificant OS benefitPERSIST-2Analysis of survivalUnique survival advantagesInhibitor of Janus kinaseJanus kinaseOS curvesRetrospective analysisSurvival advantageMyelofibrosisPacritinibPatientsRuxolitinibPlateletThrombocytopeniaVolume reductionData-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes
Komrokji R, Lanino L, Ball S, Bewersdorf J, Marchetti M, Maggioni G, Travaglino E, Al Ali N, Fenaux P, Platzbecker U, Santini V, Diez-Campelo M, Singh A, Jain A, Aguirre L, Tinsley-Vance S, Schwabkey Z, Chan O, Xie Z, Brunner A, Kuykendall A, Bennett J, Buckstein R, Bejar R, Carraway H, DeZern A, Griffiths E, Halene S, Hasserjian R, Lancet J, List A, Loghavi S, Odenike O, Padron E, Patnaik M, Roboz G, Stahl M, Sekeres M, Steensma D, Savona M, Taylor J, Xu M, Sweet K, Sallman D, Nimer S, Hourigan C, Wei A, Sauta E, D’Amico S, Asti G, Castellani G, Delleani M, Campagna A, Borate U, Sanz G, Efficace F, Gore S, Kim T, Daver N, Garcia-Manero G, Rozman M, Orfao A, Wang A, Foucar M, Germing U, Haferlach T, Scheinberg P, Miyazaki Y, Iastrebner M, Kulasekararaj A, Cluzeau T, Kordasti S, van de Loosdrecht A, Ades L, Zeidan A, Della Porta M, Syndromes I. Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes. The Lancet Haematology 2024, 11: e862-e872. PMID: 39393368, DOI: 10.1016/s2352-3026(24)00251-5.Peer-Reviewed Original ResearchGenomic featuresData-driven approachTP53 inactivationGenomic heterogeneityEntity labelsGenetic featuresDel(7q)/-7Myelodysplastic syndromeGenomic profilingData scientistsMutated SF3B1Cluster assignmentComplex karyotypeRUNX1 mutationsModified Delphi consensus processDel(5qIsolated del(5qAcute myeloid leukemiaData-drivenDelphi consensus processMarrow blastsContemporary Approach to the Diagnosis and Classification of Myelodysplastic Neoplasms/Syndromes—Recommendations From the International Consortium for Myelodysplastic Neoplasms/Syndromes (MDS [icMDS])
Aakash F, Gisriel S, Zeidan A, Bennett J, Bejar R, Bewersdorf J, Borate U, Boultwood J, Brunner A, Buckstein R, Carraway H, Churpek J, Daver N, DeZern A, Efficace F, Fenaux P, Figueroa M, Garcia-Manero G, Gore S, Greenberg P, Griffiths E, Halene S, Hourigan C, Kim T, Kim N, Komrokji R, Kutchroo V, List A, Little R, Majeti R, Nazha A, Nimer S, Odenike O, Padron E, Patnaik M, Platzbecker U, Della Porta M, Roboz G, Sallman D, Santini V, Sanz G, Savona M, Sekeres M, Stahl M, Starczynowski D, Steensma D, Taylor J, Abdel-Wahab O, Wei A, Xie Z, Xu M, Hasserjian R, Loghavi S. Contemporary Approach to the Diagnosis and Classification of Myelodysplastic Neoplasms/Syndromes—Recommendations From the International Consortium for Myelodysplastic Neoplasms/Syndromes (MDS [icMDS]). Modern Pathology 2024, 37: 100615. PMID: 39322118, DOI: 10.1016/j.modpat.2024.100615.Peer-Reviewed Original ResearchIntensive 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 patientsBeyond HMAs: Novel targets and therapeutic approaches
Getz T, Bewersdorf J, Kewan T, Stempel J, Bidikian A, Shallis R, Stahl M, Zeidan A. Beyond HMAs: Novel targets and therapeutic approaches. Seminars In Hematology 2024 PMID: 39389839, DOI: 10.1053/j.seminhematol.2024.08.001.Peer-Reviewed Original ResearchAcute myeloid leukemiaDelays progression to acute myeloid leukemiaHeterogeneous group of clonal hematopoietic disordersGroup of clonal hematopoietic disordersMolecular International Prognostic Scoring SystemRandomized phase 3 clinical trialProgression to acute myeloid leukemiaInternational Prognostic Scoring SystemLower-risk MDS patientsRisk stratification of patientsPhase 3 clinical trialsCombination of azacitidineHypomethylating agent combinationsCurrent treatment landscapeFirst line therapyPrognostic Scoring SystemBiomarker-directed therapiesClonal hematopoietic disordersLack of therapeutic agentsStratification of patientsEarly phase trialsErythropoiesis stimulating agentsTreated with therapiesVariable clinical featuresStandard of careRisk 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 modelPatientsAcute 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, ahead-of-print: 1-11. 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 implicationsTP53 Y220C mutations in patients with myeloid malignancies
Gener-Ricos G, Bewersdorf J, Loghavi S, Bataller A, Goldberg A, Sasaki K, Famulare C, Takahashi K, Issa G, Borthakur G, Kadia T, Short N, Senapati J, Carter B, Patel K, Kantarjian H, Andreeff M, Stein E, DiNardo C. TP53 Y220C mutations in patients with myeloid malignancies. Leukemia & Lymphoma 2024, 65: 1511-1515. PMID: 38856690, DOI: 10.1080/10428194.2024.2363440.Peer-Reviewed Original ResearchPrognostic impact of 'multi-hit' <i>versus</i> 'single-hit' <i>TP53</i> 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 G, 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 outcomeToward a more patient‐centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS)
Efficace F, Buckstein R, Abel G, Giesinger J, Fenaux P, Bewersdorf J, Brunner A, Bejar R, Borate U, DeZern A, Greenberg P, Roboz G, Savona M, Sparano F, Boultwood J, Komrokji R, Sallman D, Xie Z, Sanz G, Carraway H, Taylor J, Nimer S, Della Porta M, Santini V, Stahl M, Platzbecker U, Sekeres M, Zeidan A. Toward a more patient‐centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS). HemaSphere 2024, 8: e69. PMID: 38774655, PMCID: PMC11106800, DOI: 10.1002/hem3.69.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPatient-reported outcomesPatient-reported outcome dataHealth-related qualityPatient-reported outcome endpointsHealth-related quality of lifeClinical trialsImprove patients' health-related qualityPatients' health-related qualityPatient-reported outcome itemsQuality of lifeTime-to-event analysisRandomized controlled trialsTreatment decision-makingPatient carePatient populationTreatment advancesControlled trialsPatientsIncurable diseaseAssessment strategiesHRQoLBenefit/risk assessmentDrug development processTrialsTherapyCorrection to: Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Kewan T, Stahl M, Bewersdorf J, Zeidan A. Correction to: Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. Current Hematologic Malignancy Reports 2024, 19: 151-151. PMID: 38761360, DOI: 10.1007/s11899-024-00734-x.Peer-Reviewed Original ResearchCombination therapy with hypomethylating agents and venetoclax versus intensive induction chemotherapy in IDH1‐ or IDH2‐mutant newly diagnosed acute myeloid leukemia—A multicenter cohort study
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, Ramos J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Combination therapy with hypomethylating agents and venetoclax versus intensive induction chemotherapy in IDH1‐ or IDH2‐mutant newly diagnosed acute myeloid leukemia—A multicenter cohort study. American Journal Of Hematology 2024, 99: 1640-1643. PMID: 38751104, DOI: 10.1002/ajh.27366.Peer-Reviewed Original ResearchClinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes
Tentori C, Gregorio C, Robin M, Gagelmann N, Gurnari C, Ball S, Caballero Berrocal J, Lanino L, D'Amico S, Spreafico M, Maggioni G, Travaglino E, Sauta E, Meggendorfer M, Zhao L, Campagna A, Savevski V, Santoro A, Al Ali N, Sallman D, Sole F, Garcia-Manero G, Germing U, Kroger N, Kordasti S, Santini V, Sanz G, Kern W, Platzbecker U, Diez-Campelo M, Maciejewski J, Ades L, Fenaux P, Haferlach T, Zeidan A, Castellani G, Komrokji R, Ieva F, Della Porta M, Bernardi M, Di Grazia C, Vago L, Rivoli G, Borin L, Chiusolo P, Giaccone L, Voso M, Bewersdorf J, Nibourel O, Beyá M, Jerez A, Hernández F, Kennedy K, Xicoy B, Ubezio M, Russo A, Todisco G, Mannina D, Bramanti S, Zampini M, Riva E, Bicchieri M, Asti G, Viviani F, Buizza A, Tinterri B, Kubasch A, Bacigalupo A, Raiola A, Rambaldi A, Passamonti F, Ciceri F. Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes. Journal Of Clinical Oncology 2024, 42: 2873-2886. PMID: 38723212, PMCID: PMC11328926, DOI: 10.1200/jco.23.02175.Peer-Reviewed Original ResearchHematopoietic stem-cell transplantationAllogeneic hematopoietic stem-cell transplantationStem-cell transplantationMyelodysplastic syndromeIPSS-MMolecular International Prognostic Scoring SystemInternational Prognostic Scoring SystemPrognostic Scoring SystemTime of transplantationProportion of patientsHigh-risk categoryOptimal timingProlonged life expectancyRevised IPSSIPSS-RRetrospective populationValidation cohortCurative treatmentClinical relevanceTransplantationPatientsModerately high-Scoring systemAverage survivalLife expectancyCost-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 yearsTreatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Kewan T, Stahl M, Bewersdorf J, Zeidan A. Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. Current Hematologic Malignancy Reports 2024, 19: 138-150. PMID: 38632155, DOI: 10.1007/s11899-024-00733-y.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationLower-risk MDSErythropoiesis-stimulating agentsHypomethylating agentsIPSS-MHR-MDSRisk stratificationMolecular International Prognostic Scoring SystemRisk of leukemia progressionTreated with hypomethylating agentsInternational Prognostic Scoring SystemTreatment of myelodysplastic syndromesOral hypomethylating agentsHigh-risk MDSPrognostic Scoring SystemStem cell transplantationEnhanced risk stratificationRecent FindingsRecent advancesRefine treatment strategiesQuality-of-life improvementAssociated with treatmentTreatment decision-makingIntensive chemotherapyMDS patientsHypomethylating 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 treatmentComparing 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