2024
Risk 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 implicationsIntensive Induction Chemotherapy versus 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, Ramos Perez J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Intensive Induction Chemotherapy versus Hypomethylating Agents in Combination with Venetoclax in NPM1-mutant AML. Blood Advances 2024 PMID: 38941537, 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 patientsTP53 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, ahead-of-print: 1-5. PMID: 38856690, DOI: 10.1080/10428194.2024.2363440.Peer-Reviewed Original ResearchPrognostic 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 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 PMID: 38813716, 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 patientsComparing 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 ResearchHypomethylating 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 treatmentIntegrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Integrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine. Therapeutic Advances In Hematology 2024, 15: 20406207241257904. PMID: 38883163, PMCID: PMC11180421, DOI: 10.1177/20406207241257904.Peer-Reviewed Original ResearchHigher-risk myelodysplastic syndromesAcute myeloid leukemiaBone marrowMutation statusImmune landscapeImmunological landscapeAnti-PD-L1 antibody durvalumabHR-MDS patientsWild-type acute myeloid leukemiaTP53-mutant acute myeloid leukemiaMutant acute myeloid leukemiaAzacitidine-based therapyWild-type patientsImmune checkpoint proteinsImmune checkpoint expressionT cell populationsWild-typeStatistically significant decreaseAZA therapyImmunosuppressive microenvironmentPD-L1Mutant patientsDNA methylation arraysCheckpoint expressionMyelodysplastic syndrome
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 ResearchConceptsDose-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 efficacyMoving 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 coursePericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood–brain barrier function
Teske N, Dyckhoff-Shen S, Beckenbauer P, Bewersdorf J, Engelen-Lee J, Hammerschmidt S, Kälin R, Pfister H, Brouwer M, Klein M, Glass R, van de Beek D, Koedel U. Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood–brain barrier function. Journal Of Neuroinflammation 2023, 20: 267. PMID: 37978545, PMCID: PMC10655320, DOI: 10.1186/s12974-023-02938-z.Peer-Reviewed Original ResearchConceptsModel of pneumococcal meningitisPneumococcal meningitisLeukocyte infiltrationAnimal model of pneumococcal meningitisPrevented blood-brain barrierToll-like receptor inhibitorsDegree of leukocyte infiltrationSerotypes of Streptococcus pneumoniaeUnfavorable disease courseBlood-brain barrier disruptionHuman pericytesExperimental pneumococcal meningitisBlood-brain barrier integrityRegulating leukocyte infiltrationBlood-brain barrier functionRegulation of cerebral blood flowAdult mouse modelInfection in vivoUpregulation of chemokine expressionIncreased cerebral edemaMaintenance of blood-brain barrier integrityBlood-brain barrierCerebral blood flowMouse meningitis modelIn vitro studiesE7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial
Bewersdorf J, Chandhok N, Watts J, Derkach A, Abdel-Wahab O, Stein E, Taylor J. E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial. Blood 2023, 142: 1547. DOI: 10.1182/blood-2023-182369.Peer-Reviewed Original ResearchAcute myeloid leukemiaEastern Cooperative Oncology GroupPhase II clinical trialChronic myelomonocytic leukemiaMyelodysplastic syndromePatient-derived xenograftsII clinical trialsPreclinical dataSplicing factor genesMyeloid malignanciesClinical trialsAdequate end-organ functionContext of combination therapyDay 1Safety run-in phaseRefractory acute myeloid leukemiaSimon 2-stage designResponse rateDynamic BH3 profilingCycles of therapyNegative prognostic impactEvent-free survivalMyelodysplastic syndrome patientsHuman acute myeloid leukemiaPhase II trialValidation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Were Treated with Hypomethylating Agents (HMA)
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, Logothetis C, Ramaswamy R, Rose A, Roboz G, Rolles B, Wang E, Harris A, Shallis R, Xie Z, Padron E, Maciejewski J, Sallman D, Della Porta M, Komrokji R, Zeidan A. Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Were Treated with Hypomethylating Agents (HMA). Blood 2023, 142: 3240. DOI: 10.1182/blood-2023-186340.Peer-Reviewed Original ResearchComplete remission rateOverall response rateOutcome of ptsMedian overall survivalOverall survivalHypomethylating agentHMA initiationHR-MDSC-indexRisk groupsScoring systemInternational Prognostic Scoring SystemResponse criteriaPrognostic scoring systemHigh-risk diseaseLarge multicenter cohortHigh-risk groupHarrell's C-indexLog-rank testPrediction of outcomeDifferent scoring systemsSubsequent validation studiesHMA cyclesMedian followAllogeneic HSCTImpact of Type of Hypomethylating Agent (HMA) Used on Outcomes of Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) - a Large, Multicenter, Retrospective Analysis
Bewersdorf J, Kewan T, Blaha O, Stahl M, Al Ali N, DeZern A, Sekeres M, Uy G, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, McMahon C, Zeidner J, Savona M, Stempel J, Chandhok N, Ramaswamy R, Roboz G, Rolles B, Wang E, Harris A, Amaya M, Hawkins H, Grenet J, Gurnari C, Shallis R, Xie Z, Maciejewski J, Sallman D, Della Porta M, Komrokji R, Zeidan A. Impact of Type of Hypomethylating Agent (HMA) Used on Outcomes of Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) - a Large, Multicenter, Retrospective Analysis. Blood 2023, 142: 4613. DOI: 10.1182/blood-2023-178728.Peer-Reviewed Original ResearchCox multivariable regression modelOverall survivalHMA initiationHypomethylating agentMultivariable regression modelsTP53 mutationsAllo-HCTComplete remissionComplex karyotypePartner drugsBone marrowSurvival analysisAllogeneic hematopoietic cell transplantMultivariable Cox regression modelsTreatment typeOverall responseAdverse genetic featuresMedian overall survivalOutcomes of patientsHematopoietic cell transplantAdverse overall survivalKaplan-Meier methodCox regression modelLog-rank testPredictors of response