2022
Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells
North K, Benbarche S, Liu B, Pangallo J, Chen S, Stahl M, Bewersdorf J, Stanley R, Erickson C, Cho H, Pineda J, Thomas J, Polaski J, Belleville A, Gabel A, Udy D, Humbert O, Kiem H, Abdel-Wahab O, Bradley R. Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells. Nature Biotechnology 2022, 40: 1103-1113. PMID: 35241838, PMCID: PMC9288984, DOI: 10.1038/s41587-022-01224-2.Peer-Reviewed Original ResearchConceptsBreast cancerExpression of herpes simplex virus thymidine kinaseHerpes simplex virus thymidine kinaseCancer cellsPancreatic cancer cells in vitroWild-type cellsCancer cells in vitroCancer gene therapyTargeting of cancer cellsTumor-specific changesUveal melanoma cellsTreatment in vivoSynthetic intronChange-of-function mutationsCells in vitroUveal melanomaSF3B1 mutationsHSV-tkGene therapyTumor cellsIsogenic wild-type cellsMelanoma cellsRNA splicing factorsCancerHost survivalGilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors
Numan Y, Rahman Z, Grenet J, Boisclair S, Bewersdorf JP, Collins C, Barth D, Fraga M, Bixby DL, Zeidan AM, Yilmaz M, Desai P, Mannis G, Deutsch YE, Abaza Y, Dinner S, Frankfurt O, Litzow M, Al‐Kali A, Foran JM, Sproat LZ, Jovanovic B, Daver N, Perl AE, Altman JK. Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors. American Journal Of Hematology 2022, 97: 322-328. PMID: 34981560, DOI: 10.1002/ajh.26447.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaRelapsed/Refractory Acute Myeloid LeukemiaComposite complete remission rateRefractory acute myeloid leukemiaLower median overall survivalComplete remission rateMedian overall survivalStem cell transplantCRC ratesLower CRCRefractory FLT3Median survivalRemission rateIntensive inductionOverall survivalCell transplantCombination therapyFLT3 inhibitorsFLT3 mutationsClinical activityUS CentersRetrospective analysisADMIRAL studyMitogen-activated protein kinase pathwayPhase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes
Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, Burgess MR, Hege K, Stock W. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 557-569. PMID: 34981142, PMCID: PMC9414073, DOI: 10.1007/s00277-021-04734-2.Peer-Reviewed Original ResearchConceptsAnti-drug antibodiesAcute myeloid leukemiaDose-limiting toxicityRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeMyelodysplastic syndromeMyeloid leukemiaCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsADA-positive patientsPhase 2 dosePresence/frequencyUnexpected safety findingsPhase 1 studyAnti-CD47 antibodyCD47-SIRPα interactionMacrophage-mediated killingHematological cancer cell linesFebrile neutropeniaMonotherapy activityCancer cell linesPrimary endpointSecondary endpointsAdverse eventsObjective response
2020
A complex karyotype and a genetic mutation in acute myeloid leukaemia
Bewersdorf JP, Siddon A, DiAdamo A, Zeidan AM. A complex karyotype and a genetic mutation in acute myeloid leukaemia. The Lancet 2020, 396: 2018. PMID: 33341145, DOI: 10.1016/s0140-6736(20)32543-5.Peer-Reviewed Original ResearchPatterns of care and clinical outcomes with cytarabine-anthracycline induction chemotherapy for AML patients in the United States
Zeidan AM, Podoltsev NA, Wang X, Zhang C, Bewersdorf JP, Shallis RM, Huntington SF, Neparidze N, Giri S, Gore SD, Davidoff AJ, Ma X, Wang R. Patterns of care and clinical outcomes with cytarabine-anthracycline induction chemotherapy for AML patients in the United States. Blood Advances 2020, 4: 1615-1623. PMID: 32311013, PMCID: PMC7189301, DOI: 10.1182/bloodadvances.2020001728.Peer-Reviewed Original ResearchConceptsIntensive induction chemotherapyAcute myeloid leukemiaHospital deathInduction chemotherapyAdult patientsMultivariable logistic regression modelLow hospital volumePremier Healthcare DatabasePredictors of deathHealthcare resource utilizationIntensive care unitPatterns of careStandard of careLogistic regression modelsFit patientsRemission inductionFirst hospitalizationHospital volumeInpatient deathInpatient mortalityOlder patientsSupportive careMedian ageAML patientsCare unitManagement of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study
Stahl M, Shallis RM, Wei W, Montesinos P, Lengline E, Neukirchen J, Bhatt VR, Sekeres MA, Fathi AT, Konig H, Luger S, Khan I, Roboz GJ, Cluzeau T, Martínez-Cuadron D, Raffoux E, Germing U, Umakanthan JM, Mukherjee S, Brunner AM, Miller A, McMahon CM, Ritchie EK, Rodríguez-Veiga R, Itzykson R, Boluda B, Rabian F, Tormo M, Acuña-Cruz E, Rabinovich E, Yoo B, Cano I, Podoltsev NA, Bewersdorf JP, Gore S, Zeidan AM. Management of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study. Leukemia 2020, 34: 3149-3160. PMID: 32132655, PMCID: PMC8155811, DOI: 10.1038/s41375-020-0783-3.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaOverall survivalMyeloid leukemiaMultivariate analysisLong-term clinical outcomesComposite complete remissionImpact of leukapheresisManagement of hyperleukocytosisMedian overall survivalThirty-day mortalityHigh-quality evidenceWhite cell countProportional hazards modelUse of leukapheresisLogistic regression modelsSignificant resource useIntensive chemotherapyComplete remissionHazard ratioClinical outcomesInferior outcomesUnadjusted analysesQuality evidencePotential complicationsOdds ratio
2019
The golden age for patients in their golden years: The progressive upheaval of age and the treatment of newly-diagnosed acute myeloid leukemia
Shallis RM, Boddu PC, Bewersdorf JP, Zeidan AM. The golden age for patients in their golden years: The progressive upheaval of age and the treatment of newly-diagnosed acute myeloid leukemia. Blood Reviews 2019, 40: 100639. PMID: 31761380, DOI: 10.1016/j.blre.2019.100639.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInduction therapyAcute myeloid leukemia patientsMost acute myeloid leukemia (AML) patientsAML patients ageIntensive induction therapyLeukemic stem cell persistenceOptimal treatment modalityMyeloid leukemia patientsPatient-specific factorsAcute myeloid leukemiaAvailability of therapiesMedical comorbiditiesOlder patientsPatient ageIntensive therapyOrgan reserveTreatment algorithmEarly mortalityLongstanding recommendationsTreatment modalitiesSuch therapyLeukemia patientsMyeloid leukemiaPatientsTherapyTemporal patterns and predictors of receiving no active treatment among older patients with acute myeloid leukemia in the United States: A population‐level analysis
Zeidan AM, Podoltsev NA, Wang X, Bewersdorf JP, Shallis RM, Huntington SF, Gore SD, Davidoff AJ, Ma X, Wang R. Temporal patterns and predictors of receiving no active treatment among older patients with acute myeloid leukemia in the United States: A population‐level analysis. Cancer 2019, 125: 4241-4251. PMID: 31483484, PMCID: PMC7733320, DOI: 10.1002/cncr.32439.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaTime of diagnosisOlder patientsActive treatmentMyeloid leukemiaMultivariable logistic regression modelMedian overall survivalPercentage of patientsLow-intensity therapyMajority of patientsNovel therapeutic optionsQuality of careLogistic regression modelsIntensity therapyTherapy receiptOverall survivalWorse survivalClinical factorsInferior survivalEntire cohortTherapeutic optionsPatient populationRetrospective analysisHigher oddsProvider characteristicsOne 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 stageCalcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis
Witte M, Schumacher A, Mahler C, Bewersdorf J, Lehmitz J, Scheiter A, Sánchez P, Williams P, Griesbeck O, Naumann R, Misgeld T, Kerschensteiner M. Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis. Neuron 2019, 101: 615-624.e5. PMID: 30686733, PMCID: PMC6389591, DOI: 10.1016/j.neuron.2018.12.023.Peer-Reviewed Original ResearchConceptsAxonal lossModel of multiple sclerosisSodium-calcium exchangerCytoplasmic calcium levelsMultiple sclerosis modelMultiple sclerosis patientsCalcium entryCalcium influxCalcium levelsCalcium imagingCalcium accumulationGlutamate excitotoxicityPersistent disabilityAxonal degenerationMultiple sclerosisAxonsPlasma membraneEndoplasmic reticulumCalcium
2018
Challenges in HSV encephalitis: normocellular CSF, unremarkable CCT, and atypical MRI findings
Bewersdorf J, Koedel U, Patzig M, Dimitriadis K, Paerschke G, Pfister H, Klein M. Challenges in HSV encephalitis: normocellular CSF, unremarkable CCT, and atypical MRI findings. Infection 2018, 47: 267-273. PMID: 30506479, DOI: 10.1007/s15010-018-1257-7.Peer-Reviewed Original ResearchConceptsHSV encephalitisCerebrospinal fluidLevel of clinical suspicionCerebrospinal fluid cell countSpectrum of clinical presentationsMagnetic resonance imaging abnormalitiesSevere brainstem involvementTemporal lobe hemorrhageTreated with acyclovirFocal neurological deficitsLife-saving therapyAcyclovir therapyClinical suspicionBrainstem involvementAtypical presentationClinical presentationAtypical findingsDiagnostic challengeClinical featuresDelayed administrationLaboratory findingsClinical outcomesCT scanSimplex virusNeurological deficits
2017
Generic atorvastatin is as effective as the brand-name drug (LIPITOR®) in lowering cholesterol levels: a cross-sectional retrospective cohort study
Loch A, Bewersdorf J, Kofink D, Ismail D, Abidin I, Veriah R. Generic atorvastatin is as effective as the brand-name drug (LIPITOR®) in lowering cholesterol levels: a cross-sectional retrospective cohort study. BMC Research Notes 2017, 10: 291. PMID: 28716156, PMCID: PMC5514478, DOI: 10.1186/s13104-017-2617-6.Peer-Reviewed Original ResearchConceptsStatistically significant differenceEffective management of hyperlipidemiaHealth care costsSignificant differenceUniversity of Malaya Medical CentreRetrospective cohort studyHDL cholesterol levelsManagement of hyperlipidemiaLipid lowering effectsIncreased health care costsAtorvastatin formulationsLowering cholesterol levelsSwitching patientsCare costsLDL cholesterolMethodsThis cross-sectionalCohort studyLipid profileTotal cholesterolGeneric atorvastatinDrug efficacyAtorvastatinMedical CentreCholesterol levelsPatientsEarly and aggressive ISR with a polymer- and carrier-free drug-coated stent system
Loch A, Bewersdorf J, Veeriah R. Early and aggressive ISR with a polymer- and carrier-free drug-coated stent system. Indian Heart Journal 2017, 69: 651-654. PMID: 29054192, PMCID: PMC5650585, DOI: 10.1016/j.ihj.2017.03.002.Peer-Reviewed Original Research