2024
Mis-Splicing Derived Neoantigens and Cognate T Cell Receptors in Splicing Factor Mutant Myeloid Neoplasms
Kim W, Crosse E, De Neef E, Etxeberria I, Sabio E, Wang E, Bewersdorf J, Lu S, Belleville A, Fox N, Castro C, Zhang P, Fujino T, Lewis J, Rahman J, Zhang B, Winick J, Lewis A, Stanley R, Dewolf S, Meskauskaite Urben B, Takizawa M, Krause T, Molina H, Chaligne R, Koppikar P, Molldrem J, Gigoux M, Merghoub T, Daniyan A, Greenbaum B, Klebanoff C, Bradley R, Abdel-Wahab O. Mis-Splicing Derived Neoantigens and Cognate T Cell Receptors in Splicing Factor Mutant Myeloid Neoplasms. Blood 2024, 144: 343-343. DOI: 10.1182/blood-2024-198639.Peer-Reviewed Original ResearchCD8+ T cellsT cell receptorPrimary human T cellsHuman T cellsT cellsHLA-ILeukemic cellsSRSF2 mutationsHealthy donorsIsolated CD8+ T cellsGraft-versus-leukemia effectT cell cytotoxic functionTCR-T cell therapyVirus-reactive T cellsAllogeneic stem cell transplantationT cell-based immunotherapyT cell receptor clonotypesLyse leukemic cellsPatient PBMC samplesCognate T cell receptorsDonor T cellsHigh-risk MDSStem cell transplantationHLA class IMis-splicingOutcomes with HMA Plus Venetoclax Vs Intensive Chemotherapy in AML Patients with Chromosome 5 and 7 Abnormalities
Boussi L, Bewersdorf J, Liu Y, Shallis R, Aguirre L, Zucenka A, Garciaz S, Bystrom R, DeAngelo D, Stone R, Luskin M, Garcia J, Winer E, Chen E, Wadleigh M, Ling K, Zeidan A, Goldberg A, Stein E, Shimony S, Stahl M. Outcomes with HMA Plus Venetoclax Vs Intensive Chemotherapy in AML Patients with Chromosome 5 and 7 Abnormalities. Blood 2024, 144: 4281-4281. DOI: 10.1182/blood-2024-204467.Peer-Reviewed Original ResearchAcute myeloid leukemiaMedian OSTP53 co-mutationsTreated with ICIntensive chemotherapyComposite CRCo-mutationsComplete remissionOverall survivalPts ageAllogeneic stem cell transplantationSecondary acute myeloid leukemiaDiagnosed AMLAcute myeloid leukemia patientsAssociated with poor outcomesEstimate overall survivalStem cell transplantationKaplan-Meier methodLog-rank testPredictors of survivalCPX-351Monosomy 5MRD negativityInduction therapyComplex karyotypeThe 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 therapyEfficacy and Safety of Pembrolizumab Added to Azacitidine Plus Venetoclax for Patients with Acute Myeloid Leukemia: Results from an Investigator-Initiated, Multi-Center, CTEP-Sponsored Randomized, Phase II Trial (BLAST AML-2)
Stempel J, Uy G, Dinner S, Gojo I, Reed D, Roy R, Byrd K, Yerrabothala S, Lai C, Doucette K, Caldwell A, Blaha O, Podoltsev N, Mendez L, Bewersdorf J, Kewan T, Wistuba I, Alatrash G, Haymaker C, Streicher H, Sharon E, Little R, Gore S, Radich J, Wood B, Zeidan A, Shallis R. Efficacy and Safety of Pembrolizumab Added to Azacitidine Plus Venetoclax for Patients with Acute Myeloid Leukemia: Results from an Investigator-Initiated, Multi-Center, CTEP-Sponsored Randomized, Phase II Trial (BLAST AML-2). Blood 2024, 144: 736. DOI: 10.1182/blood-2024-210370.Peer-Reviewed Original ResearchPhase II trialTreatment-related AEsII trialFrequent treatment-related AEsSafety run-in periodAllogeneic stem cell transplantationNo dose limiting toxicitiesRandomized phase II trialAML-2Multi-centerControl armSafety of pembrolizumabDose-limiting toxicityPD-1 inhibitionAnti-PD1 antibodyIncomplete count recoveryFLT3 wild-typeIntermediate cytogenetic riskStem cell transplantationAcute myeloid leukemiaActivated T cellsRun-in periodIntention-to-treat analysisCancer Immune MonitoringLong-term survivalToxicity 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 methodIntensive 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 implications
2023
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
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 exposureSurvival of TP53-mutated acute myeloid leukemia patients receiving allogeneic stem cell transplantation after first induction or salvage therapy: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Atallah E, Shallis R, Saliba A, Patel A, Bewersdorf J, Grenet J, Stahl M, Duvall A, Burkart M, Palmisiano N, Bradshaw D, Kubiak M, Dinner S, Goldberg A, Abaza Y, Murthy G, Kota V, Litzow M. Survival of TP53-mutated acute myeloid leukemia patients receiving allogeneic stem cell transplantation after first induction or salvage therapy: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Leukemia 2023, 37: 799-806. PMID: 36807649, DOI: 10.1038/s41375-023-01847-7.Peer-Reviewed Original ResearchConceptsEvent-free survivalAllo-HSCTOverall survivalChronic GVHDAllogeneic hematopoietic stem cell transplantAllogeneic stem cell transplantationMedian event-free survivalHematopoietic stem cell transplantAcute myeloid leukemia patientsMedian overall survivalPost allo-HSCTReduced intensity conditioningStem cell transplantStem cell transplantationLong-term outcomesMyeloid leukemia patientsMulti-center studyAcute graftComplete remissionHost diseaseSalvage therapyComplex cytogeneticsMyeloablative conditioningMedian ageCell transplant
2022
Disparities in receiving disease‐directed therapy, allogeneic stem cell transplantation in non‐Hispanic Black patients with TP53‐mutated acute myeloid leukemia
Badar T, Litzow M, Shallis R, Patel A, Saliba A, Burkart M, Bewersdorf J, Stahl M, De Camargo Correia G, Murthy S, Abaza Y, Duvall A, Bradshaw D, Kota V, Dinner S, Goldberg A, Palmisiano N, Al Kali A, Atallah E. Disparities in receiving disease‐directed therapy, allogeneic stem cell transplantation in non‐Hispanic Black patients with TP53‐mutated acute myeloid leukemia. Cancer 2022, 129: 934-945. PMID: 36545710, DOI: 10.1002/cncr.34604.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAllogeneic stem cell transplantationNHB patientsStem cell transplantationNHW patientsCell transplantationMyeloid leukemiaTherapy-related acute myeloid leukemiaNon-Hispanic black patientsCurative-intent therapyLow-intensity chemotherapyBest supportive careComplete response rateMedian patient ageProportion of patientsSubset of patientsDisease-directed therapyHigher proportionIntensive chemotherapyPatient ageSupportive careBlack patientsClinical outcomesTreatment disparitiesRetrospective studyMolecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia
Stahl M, Derkach A, Farnoud N, Bewersdorf J, Robinson T, Famulare C, Cho C, Devlin S, Menghrajani K, Patel M, Cai S, Miles L, Bowman R, Geyer M, Dunbar A, Epstein‐Peterson Z, McGovern E, Schulman J, Glass J, Taylor J, Viny A, Stein E, Getta B, Arcila M, Gao Q, Barker J, Shaffer B, Papadopoulos E, Gyurkocza B, Perales M, Abdel‐Wahab O, Levine R, Giralt S, Zhang Y, Xiao W, Pai N, Papaemmanuil E, Tallman M, Roshal M, Goldberg A. Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia. American Journal Of Hematology 2022, 98: 79-89. PMID: 36251406, PMCID: PMC10080561, DOI: 10.1002/ajh.26757.Peer-Reviewed Original ResearchConceptsMeasurable residual diseaseAcute myeloid leukemiaAllo-SCTInduction chemotherapyPersistent diseaseMyeloid leukemiaAllogeneic stem cell transplantationStem cell transplantationMonosomy 5Residual diseaseDisease clearanceKaryotypic abnormalitiesPrognostic factorsCell transplantationMolecular predictorsMRD clearanceRemissionClinical trialsNext-generation sequencingChemotherapyPatientsMutation patternsTherapyLeukemiaMRDRacial disparities in patients with TP53 mutated acute myeloid leukemia.
Badar T, Litzow M, Shallis R, Stahl M, Bewersdorf J, Saliba A, de Camargo Correia G, Patel A, Abaza Y, Murthy S, Duvall A, Burkart M, Al-Kali A, Palmisiano N, Dinner S, Goldberg A, Atallah E. Racial disparities in patients with TP53 mutated acute myeloid leukemia. Journal Of Clinical Oncology 2022, 40: e19007-e19007. DOI: 10.1200/jco.2022.40.16_suppl.e19007.Peer-Reviewed Original ResearchAcute myeloid leukemiaBlacks/HispanicsSupportive careClinical outcomesMyeloid leukemiaTherapy-related acute myeloid leukemiaMedian event-free survivalAllogeneic stem cell transplantationRacial disparitiesCurative-intent therapySubset of ptsEvent-free survivalHigh-risk diseaseStem cell transplantationHigher proportionHigh rateRace/ethnicityAML ptsBaseline characteristicsComplete remissionCPX-351Free survivalComplex cytogeneticsMedian agePoor OS
2021
Multicenter Analysis of Treatment and Outcomes for Patient with TP53 Mutated AML in the Era of Novel Therapies; Significant Impact of Allogeneic Stem Cell Transplantation on Survival
Badar T, Litzow M, Shallis R, Bewersdorf J, Saliba A, De Camargo Correia G, Stahl M, Goldberg A, Atallah E, Foran J. Multicenter Analysis of Treatment and Outcomes for Patient with TP53 Mutated AML in the Era of Novel Therapies; Significant Impact of Allogeneic Stem Cell Transplantation on Survival. Blood 2021, 138: 797. DOI: 10.1182/blood-2021-147639.Peer-Reviewed Original ResearchCR/CRiProportion of patientsStem cell transplantationComplex cytogeneticsVariant allele frequencyCPX-351Overall survivalAML patientsNovel therapiesTP53 mutationsCell transplantationUnivariate analysisAllogeneic hematopoietic stem cell transplantationMedian progression-free survivalAllogeneic stem cell transplantationHematopoietic stem cell transplantationAdvisory CommitteeAML induction therapyExtra-medullary diseaseHigh-risk AMLInduction/consolidationVenetoclax combination therapyVenetoclax-based regimensMedian overall survivalMulticenter observational study
2019
One plus one does not always equal two, especially with regard to hypomethylating agents: the question of synergy of azacitidine and lenalidomide for treatment of relapsed acute myeloid leukemia and myelodysplastic syndromes post allogeneic hematopoietic stem cell transplant
Bewersdorf JP, Stahl M, Zeidan AM. One plus one does not always equal two, especially with regard to hypomethylating agents: the question of synergy of azacitidine and lenalidomide for treatment of relapsed acute myeloid leukemia and myelodysplastic syndromes post allogeneic hematopoietic stem cell transplant. Expert Review Of Hematology 2019, 12: 575-578. PMID: 31225770, DOI: 10.1080/17474086.2019.1635005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntigens, CDAzacitidineCD8-Positive T-LymphocytesClinical Trials as TopicDrug Therapy, CombinationFemaleHematopoietic Stem Cell TransplantationHumansLenalidomideLeukemia, Myeloid, AcuteLymphocyte Activation Gene 3 ProteinMaleMiddle AgedMyelodysplastic SyndromesProgrammed Cell Death 1 ReceptorRecurrenceTransplantation, HomologousConceptsAcute myeloid leukemiaHematopoietic stem cell transplantStem cell transplantMyelodysplastic syndromeMyeloid leukemiaAllo-HSCTCell transplantAllogeneic hematopoietic stem cell transplantResponse rateAllogeneic stem cell transplantationNovel salvage therapiesPhase Ib studyStem cell transplantationOverall response rateCycles of treatmentCases of graftHigh response rateMechanism of actionCombination lenalidomideSalvage therapyHost diseaseMost patientsCurative treatmentCombination therapyDisease stage