2024
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.
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 outcome
2023
TP53 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 assayImpact 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 responseValidation of the Composite Complete Response (cCR) Definitions in the International Working Group (IWG) 2023 Criteria in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Treated with Hypomethylating Agents (HMA) - a Large, Multicenter, Retrospective Analysis from the Validate Database
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, Logothetis C, Roboz G, Rolles B, Wang E, Harris A, Amaya M, Hawkins H, Grenet J, Shallis R, Xie Z, Maciejewski J, Sallman D, Della Porta M, Komrokji R, Zeidan A. Validation of the Composite Complete Response (cCR) Definitions in the International Working Group (IWG) 2023 Criteria in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Treated with Hypomethylating Agents (HMA) - a Large, Multicenter, Retrospective Analysis from the Validate Database. Blood 2023, 142: 324. DOI: 10.1182/blood-2023-180299.Peer-Reviewed Original ResearchImproved OSHypomethylating agentHMA initiationMedian OSResponse assessmentTP53 mutationsResponse definitionsPartial hematologic recoveryPredictors of OSMultivariable Cox modelBone marrow blastsKaplan-Meier analysisLog-rank testOverall response rateEfficacy of therapyMultivariable regression modelsReal-world analysisAllo-HCTBM assessmentBM evaluationHemoglobin thresholdHematologic recoveryMarrow blastsMedian durationMedian ageData-Driven Harmonization of 2022 Who and ICC Classifications of Myelodysplastic Syndromes/Neoplasms (MDS): A Study By the International Consortium for MDS (icMDS)
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, Borate U, Sanz G, Efficace F, Gore S, Kim T, Daver N, Garcia-Manero G, Rozman M, Orfao A, Wang S, 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, Komrokji R, Della Porta M. Data-Driven Harmonization of 2022 Who and ICC Classifications of Myelodysplastic Syndromes/Neoplasms (MDS): A Study By the International Consortium for MDS (icMDS). Blood 2023, 142: 998. DOI: 10.1182/blood-2023-186580.Peer-Reviewed Original ResearchBlast countMost patientsTP53 mutationsTET2 mutationsChromosomal abnormalitiesMore TP53 mutationsBone marrow blastsGene mutationsSF3B1 mutationsClinical decision-making processHigh-risk mutationsMarrow blastsMultilineage dysplasiaPatient characteristicsAML patientsClinical entityInternational cohortSHAP analysisMDS casesPatientsClinical relevanceCytogenetic abnormalitiesClinical settingComplex karyotypeU2AF1 mutations
2021
The Current Understanding of and Treatment Paradigm for Newly-Diagnosed TP53-Mutated Acute Myeloid Leukemia
Shallis R, Stahl M, Bewersdorf J, Zeidan A. The Current Understanding of and Treatment Paradigm for Newly-Diagnosed TP53-Mutated Acute Myeloid Leukemia. Hemato 2021, 2: 748-763. DOI: 10.3390/hemato2040051.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyeloid leukemiaTherapy-related acute myeloid leukemiaMeasurable residual disease statusHematopoietic stem cell transplantationMedian overall survivalResidual disease statusStem cell transplantationCurrent treatment approachesIntensive chemotherapyIntensive regimensRemission rateCytogenetic riskOverall survivalWorse prognosisCell transplantationConditioning intensityTreatment paradigmTreatment approachesTP53 mutationsDisease statusBiological subsetsPatientsPrognosisLeukemiaImmune and Epigenetic Landscape of TP53-mutated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS)
Zeidan A, Bewersdorf J, Hasle V, Thompson E, de Menezes D, Rose S, Boss I, Fox B. Immune and Epigenetic Landscape of TP53-mutated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS). Blood 2021, 138: 3371. DOI: 10.1182/blood-2021-146329.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeAcute myeloid leukemiaBristol-Myers SquibbCurrent equity holderPoor-risk cytogeneticsVariant allele frequencyAML ptsOverall response rateTrials CommitteeMedian OSTP53 mutationsMyeloid neoplasmsFlow cytometryPeripheral bloodT cell genesHigh expressionBone marrowAverage variant allele frequencyRandomized phase 2 studyBone marrow flow cytometryT-cell gene signatureTumor cellsBM blast percentageIPSS-R scoreMulticenter 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