2024
Targeted 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 treatmentIntensive 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, 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 implicationsPrognostic 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 outcomeCost-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 years
2023
Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic Syndromes (MDS)
Tentori C, Gregorio C, Robin M, Gagelmann N, Gurnari C, Ball S, Berrocal J, Lanino L, D'Amico S, Spreafico M, Maggioni G, Travaglino E, Sauta E, Meggendorfer M, Zhao L, Bernardi M, Di Grazia C, Vago L, Rivoli G, Borin L, Chiusolo P, Giaccone L, Voso M, Bewersdorf J, Nibourel O, Díaz-Beyá M, Jerez A, Hernandez F, Kennedy K, Xicoy B, Ubezio M, Campagna A, Russo A, Todisco G, Mannina D, Bramanti S, Zampini M, Riva E, Bicchieri M, Asti G, Viviani F, Buizza A, Tinterri B, Bacigalupo A, Rambaldi A, Passamonti F, Ciceri F, Savevski V, Santoro A, Al Ali N, Sallman D, Sole F, Garcia-Manero G, Germing U, Kordasti S, Santini V, Sanz G, Kern W, Kubasch A, Platzbecker U, Diez-Campelo M, Maciejewski J, Ades L, Fenaux P, Haferlach T, Zeidan A, Castellani G, Komrokji R, Ieva F, Della Porta M. Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic Syndromes (MDS). Blood 2023, 142: 197. DOI: 10.1182/blood-2023-182194.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationStem cell transplantationMyelodysplastic syndromeProlonged life expectancyClinical outcomesOptimal timingCell transplantationLife expectancyValidation cohortImmediate transplantationTransplantation policyRisks of HSCTImmediate hematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationAge groupsDiagnosis of MDSConventional prognostic scoresPost-HSCT outcomesLow-risk diseaseTiming of transplantationDisease-modifying therapiesEarly disease stagesPatient's life expectancyAverage survival timeDifferent time pointsClinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs)
Zeidan A, Mearns E, Ng C, Shah A, Lamarre N, Yellow-Duke A, Alrawashdh N, Yang B, Cheng W, Bui C, Svensson A. Clinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs). Clinical Lymphoma Myeloma & Leukemia 2023, 24: 177-186. PMID: 37996264, DOI: 10.1016/j.clml.2023.10.010.Peer-Reviewed Original ResearchEvent-free survivalAcute myeloid leukemiaMedian overall survivalOverall survivalHypomethylating agentExcess blastsRefractory anemiaReal-world settingMedian event-free survivalFirst-line therapyHematopoietic cell transplantationEligible patientsClinical outcomesCancer RegistryCell transplantationClinical benefitMedicare databaseClinical effectivenessAML progressionClinical trialsPatient outcomesMyeloid leukemiaPatientsOverall populationSignificant differencesOral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress
Venugopal S, Shallis R, Zeidan A. Oral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress. Expert Review Of Anticancer Therapy 2023, 23: 903-911. PMID: 37470508, DOI: 10.1080/14737140.2023.2238897.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaOral therapyMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationDisease-related complicationsDisease-directed therapyStem cell transplantationQuality of lifeCC-486HR-MDSOral azacitidineClinic visitsMost patientsGood tolerabilityIntensive therapyOptimal regimensCell transplantationTherapy combinationsTreatment optionsMedication administrationPatient outcomesMyeloid neoplasmsClinical developmentMyeloid malignanciesSTIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2
Zeidan A, Giagounidis A, Sekeres M, Xiao Z, Sanz G, Van Hoef M, Ma F, Hertle S, Santini V. STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Future Oncology 2023, 19: 631-642. PMID: 37083373, DOI: 10.2217/fon-2022-1237.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaMyelodysplastic syndromeCMML-2Tim-3Hematopoietic stem cell transplantationT-cell immunoglobulin domainMucin domain 3Risk myelodysplastic syndromesPhase III trialsStem cell transplantationLeukemic stem cellsFavorable tolerabilityIII trialsNovel immunotherapiesPoor outcomeCell transplantationLeukemic blastsClinical trialsNovel therapiesMyelomonocytic leukemiaDurable benefitImmune systemMyeloid malignanciesMeaningful improvements
2022
Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients
Boyiadzis M, Zhang M, Chen K, Abdel-Azim H, Abid M, Aljurf M, Bacher U, Badar T, Badawy S, Battiwalla M, Bejanyan N, Bhatt V, Brown V, Castillo P, Cerny J, Copelan E, Craddock C, Dholaria B, Perez M, Ebens C, Gale R, Ganguly S, Gowda L, Grunwald M, Hashmi S, Hildebrandt G, Iqbal M, Jamy O, Kharfan-Dabaja M, Khera N, Lazarus H, Lin R, Modi D, Nathan S, Nishihori T, Patel S, Pawarode A, Saber W, Sharma A, Solh M, Wagner J, Wang T, Williams K, Winestone L, Wirk B, Zeidan A, Hourigan C, Litzow M, Kebriaei P, de Lima M, Page K, Weisdorf D. Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients. Leukemia 2022, 37: 1006-1017. PMID: 36310182, PMCID: PMC10148918, DOI: 10.1038/s41375-022-01738-3.Peer-Reviewed Original ResearchConceptsPrimary induction failureAllo-HCTRIC allo-HCTComplete remissionOverall survivalConsolidation therapyAML patientsDetectable MRDRelapse riskInduction cyclesAllogeneic hematopoietic cell transplantationConsolidation cyclesPre-transplant inductionFirst complete remissionAdult AML patientsReduced-intensity conditioningBetter overall survivalHematopoietic cell transplantationRisk of relapseAllogeneic transplant outcomesCIBMTR analysisImproved OSInduction failureTransplant outcomesCell transplantationTreatment of myelodysplastic syndromes in the era of precision medicine and immunomodulatory drugs: a focus on higher-risk disease
Mohty R, Al Hamed R, Bazarbachi A, Brissot E, Nagler A, Zeidan A, Mohty M. Treatment of myelodysplastic syndromes in the era of precision medicine and immunomodulatory drugs: a focus on higher-risk disease. Journal Of Hematology & Oncology 2022, 15: 124. PMID: 36045390, PMCID: PMC9429775, DOI: 10.1186/s13045-022-01346-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk diseaseMyelodysplastic syndromeAcute myeloid leukemiaHeterogeneous clonal diseaseHematopoietic cell transplantationRisk of progressionDifferent hematologic malignanciesImmune therapyImmunomodulatory drugsCell transplantationHematologic malignanciesMyeloid leukemiaNovel therapiesMyeloid neoplasmsTherapeutic approachesClonal diseaseDisease pathophysiologyDiseasePrecision medicineSyndromeTherapyVariable degreesCytopeniasTransplantationMalignancyAre We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?
Shallis RM, Bewersdorf JP, Stahl MF, Halene S, Zeidan AM. Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia? Cancers 2022, 14: 2434. PMID: 35626039, PMCID: PMC9140008, DOI: 10.3390/cancers14102434.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationCD47/SIRPαIntensive induction therapyAvailable therapeutic optionsStem cell transplantationStandard of careAvailable clinical dataTesting of agentsInduction therapyMedian overallRefractory settingAggressive treatmentTim-3Immune checkpointsPreclinical rationaleTherapeutic optionsCell transplantationEfficacy dataClinical dataPatientsMolecular subgroupsTherapeutic agents
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 subsetsPatientsPrognosisLeukemiaPhase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes.
Zeidan A, Garcia J, Fenaux P, Platzbecker U, Miyazaki Y, Xiao Z, Zhou Y, Naqvi K, Kye S, Garcia-Manero G. Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes. Journal Of Clinical Oncology 2021, 39: tps7054-tps7054. DOI: 10.1200/jco.2021.39.15_suppl.tps7054.Peer-Reviewed Original ResearchHematopoietic stem cell transplantOverall survivalAcute myeloid leukemiaCR rateComplete remissionTransfusion independenceCell transplantationDisease progressionMyeloid leukemiaDay 1B-cell lymphoma-2 inhibitorRed blood cell transfusion independenceHigh-risk myelodysplastic syndromeAllogenic stem cell transplantationCo-morbid patientsIWG 2006 criteriaPhase 1b studyPlatelet transfusion independenceMedian overall survivalFirst-line treatmentPhase 3 studyBone marrow blastsDe novo patientsHematopoietic cell transplantationStudy days 1
2019
Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges
Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Reviews 2019, 36: 70-87. PMID: 31101526, DOI: 10.1016/j.blre.2019.04.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaPatient outcomesMyeloid leukemiaAllogeneic stem cell transplantationEtiology of AMLMinority of patientsStem cell transplantationAge-adjusted incidenceMost older individualsMyeloid progenitor cellsIntensive chemotherapyActive therapyClear etiologyOlder patientsRefractory diseaseSupportive careCurative therapyMedian agePoor prognosisShorter survivalCell transplantationDisease characteristicsEnvironmental DNA-damaging agentsMalignant disordersTherapeutic advances
2018
Epidemiology of myelodysplastic syndromes: Why characterizing the beast is a prerequisite to taming it
Zeidan AM, Shallis RM, Wang R, Davidoff A, Ma X. Epidemiology of myelodysplastic syndromes: Why characterizing the beast is a prerequisite to taming it. Blood Reviews 2018, 34: 1-15. PMID: 30314642, DOI: 10.1016/j.blre.2018.09.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCase ascertainmentAllogeneic hematopoietic stem cell transplantationAnnual age-adjusted incidenceHematopoietic stem cell transplantationOutcomes of patientsAge-adjusted incidenceStem cell transplantationAcute myeloid leukemiaTraditional morphologic assessmentClassification of MDSVariable cytopeniasCell transplantationMyelodysplastic syndromePrior receiptInefficient hematopoiesisEffective therapyMale genderRisk factorsMyeloid leukemiaEpidemiological trendsTreatment decisionsMyeloid neoplasmsEpidemiological assessmentDiagnostic criteriaTemporal improvementLong-term follow-up of a single institution pilot study of sirolimus, tacrolimus, and short course methotrexate for graft versus host disease prophylaxis in mismatched unrelated donor allogeneic stem cell transplantation
Kim TK, DeVeaux M, Stahl M, Perreault S, Isufi I, Cooper D, Foss F, Shlomchik W, Zelterman D, Zeidan AM, Seropian S. Long-term follow-up of a single institution pilot study of sirolimus, tacrolimus, and short course methotrexate for graft versus host disease prophylaxis in mismatched unrelated donor allogeneic stem cell transplantation. Annals Of Hematology 2018, 98: 237-240. PMID: 30027436, DOI: 10.1007/s00277-018-3427-1.Peer-Reviewed Original ResearchConceptsUnrelated donor allogeneic stem cell transplantationDonor allogeneic stem cell transplantationAllogeneic stem cell transplantationSingle-institution pilot studyHost disease (GVHD) prophylaxisShort-course methotrexateStem cell transplantationDisease prophylaxisCell transplantationPilot studyProphylaxisTacrolimusSirolimusTransplantationMethotrexateGraftAllogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study
Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, Majhail N, Barnard J, Podoltsev NA, Brunner AM, Komrokji RS, Bhatt VR, Al-Kali A, Cluzeau T, Santini V, Roboz GJ, Fenaux P, Litzow M, Fathi AT, Perreault S, Kim TK, Prebet T, Vey N, Verma V, Kobbe G, Bergua J, Serrano J, Gore SD, Zeidan AM. Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study. Transplantation And Cellular Therapy 2018, 24: 1754-1758. PMID: 29649620, DOI: 10.1016/j.bbmt.2018.03.025.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationHMA therapyStem cell transplantationComplete remissionCell transplantationUnrelated hematopoietic stem cell transplantationInternational retrospective studyLimited treatment optionsAcute myeloid leukemiaChronic GVHDMedian OSPrimary refractoryRR-AMLConditioning regimenRefractory AMLPatients patientsUnrelated donorsEntire cohortPoor prognosisRetrospective studyTreatment optionsMyeloid leukemiaInternational cohortHypomethylating agentInotuzumab ozogamicin in the treatment of relapsed/refractory acute B cell lymphoblastic leukemia
Uy N, Nadeau M, Stahl M, Zeidan AM. Inotuzumab ozogamicin in the treatment of relapsed/refractory acute B cell lymphoblastic leukemia. Journal Of Blood Medicine 2018, 9: 67-74. PMID: 29713210, PMCID: PMC5908210, DOI: 10.2147/jbm.s136575.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsChemotherapy-based approachesInotuzumab ozogamicinAcute lymphoblastic leukemiaB-ALLLymphoblastic leukemiaChimeric antigen receptor (CAR) T-cell productBispecific T-cell engager blinatumomabAcute B-cell lymphoblastic leukemiaPhiladelphia chromosome-positive diseaseSecond-line salvage therapyB-cell lymphoblastic leukemiaExcellent clinical activityT-cell productsRelapsed B-ALLCD22 monoclonal antibodySalvage therapyAdult patientsSupportive careCell transplantationLeukemic blastsSuperior survivalClinical trialsClinical activityOzogamicinClinical data
2017
Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation
Zeidan AM, Stahl M, Hu X, Wang R, Huntington SF, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation. Blood 2017, 131: 818-821. PMID: 29259002, PMCID: PMC6410557, DOI: 10.1182/blood-2017-10-811729.Peer-Reviewed Original Research