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 ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsHistone Deacetylase InhibitorsHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesConceptsDose-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 efficacySupportive Care for Patients With Myelodysplastic Syndromes
Stempel J, Podoltsev N, Dosani T. Supportive Care for Patients With Myelodysplastic Syndromes. The Cancer Journal 2023, 29: 168-178. PMID: 37195773, DOI: 10.1097/ppo.0000000000000661.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBlood TransfusionChemopreventionCOVID-19HumansIron OverloadLeukemia, Myeloid, AcuteMyelodysplastic SyndromesPalliative CareConceptsMyelodysplastic syndromeMyeloid leukemiaLow-risk diseaseTreatment-related complicationsSupportive care interventionsSupportive care measuresAcute myeloid leukemiaBone marrow disordersAntimicrobial prophylaxisFrequent complicationProgressive cytopeniasSupportive careTransfusion supportHigh-risk counterpartsBetter prognosisPalliative careRoutine immunizationCare measuresCare interventionsIneffective hematopoiesisIron overloadCommon causeMarrow disordersSyndrome populationPatientsImpact of Prophylactic Antibacterials on Coagulation Profiles and Bleeding in Patients with Acute Myeloid Leukemia/Myelodysplastic Syndrome
Allen C, Gautam S, Cheng W, Pine A, Podoltsev N, Zeidan A, Lee A, Shallis R. Impact of Prophylactic Antibacterials on Coagulation Profiles and Bleeding in Patients with Acute Myeloid Leukemia/Myelodysplastic Syndrome. Acta Haematologica 2023, 146: 287-292. PMID: 37166332, DOI: 10.1159/000530153.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesRetrospective StudiesConceptsAML/myelodysplastic syndromeAcute myeloid leukemiaInternational normalized ratioAntibacterial prophylaxisMyelodysplastic syndromeProphylactic antibacterialsCoagulation profileAcute myeloid leukemia/myelodysplastic syndromeDiagnosis of AMLHigher international normalized ratioLeukemia/myelodysplastic syndromePartial thromboplastin time prolongationYale-New Haven HospitalYale-New HavenRetrospective cohort studyAbnormal coagulation profileGroup of patientsTime of admissionHigh rateIndividual patient encountersInstitutional review boardAntibacterial exposureRelevant bleedingAdult patientsCohort studySecond malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea
Wang R, Shallis R, Stempel JM, Huntington SF, Zeidan AM, Gore SD, Ma X, Podoltsev NA. Second malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea. Blood Advances 2023, 7: 734-743. PMID: 35917456, PMCID: PMC9989521, DOI: 10.1182/bloodadvances.2022008259.Peer-Reviewed Original ResearchConceptsSecond malignanciesAcute myeloid leukemiaOlder patientsMyelodysplastic syndromeMyeloproliferative neoplasmsHU usersHigh riskPolycythemia veraEssential thrombocythemiaRisk of SMAML/myelodysplastic syndromeClassical Philadelphia chromosome-negative myeloproliferative neoplasmsImpact of hydroxyureaRetrospective cohort studyUse of hydroxyureaPhiladelphia chromosome-negative myeloproliferative neoplasmsClassical myeloproliferative neoplasmsCumulative incidence probabilityCohort studyCytoreductive therapyPatient characteristicsMedian ageHU useMyeloid leukemiaSecondary myelofibrosis
2021
Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation–A Systematic Review and Meta-Analysis
Bewersdorf JP, Allen C, Mirza AS, Grimshaw AA, Giri S, Podoltsev NA, Gowda L, Cho C, Tallman MS, Zeidan AM, Stahl M. Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation–A Systematic Review and Meta-Analysis. Transplantation And Cellular Therapy 2021, 27: 997.e1-997.e11. PMID: 34551341, PMCID: PMC9533376, DOI: 10.1016/j.jtct.2021.09.005.Peer-Reviewed Original ResearchMeSH KeywordsFms-Like Tyrosine Kinase 3Graft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesProtein Kinase InhibitorsConceptsAcute myeloid leukemiaRelapse-free survivalMaintenance therapyMyelodysplastic syndromeFLT3 inhibitorsAllo-HCTHazard ratioMaintenance treatmentClinical trialsMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationControl groupSystematic reviewAllogeneic hematopoietic cell transplantMeasurable residual disease statusHematopoietic stem cell transplantationMeasurable residual disease testingNon-relapse mortalityHematopoietic cell transplantPre-emptive treatmentResidual disease statusStem cell transplantationFavorable safety profileSame patient cohortRandom-effects modelClinical effectiveness of DNA methyltransferase inhibitors and lenalidomide in older patients with refractory anemia with ring sideroblasts: a population-based study in the United States
Wang X, Zeidan AM, Wang R, Bewersdorf JP, Zhang C, Podoltsev NA, Huntington SF, Gore SD, Ma X. Clinical effectiveness of DNA methyltransferase inhibitors and lenalidomide in older patients with refractory anemia with ring sideroblasts: a population-based study in the United States. Leukemia & Lymphoma 2021, 62: 2438-2447. PMID: 33899659, DOI: 10.1080/10428194.2021.1913142.Peer-Reviewed Original ResearchConceptsPopulation-based studyDNA methyltransferase inhibitorRARS patientsRefractory anemiaRing sideroblastsRed blood cell transfusion independenceEnd Results-Medicare databaseLower-risk myelodysplastic syndromesPopulation-based cohortMethyltransferase inhibitorRBC-TIMedian durationMedian survivalOlder patientsTransfusion independenceTreatment initiationMyelodysplastic syndromeClinical effectivenessBetter survivalLenalidomideTreatment groupsPatientsRS statusOlder adultsAnemia
2020
Persistent leukocytosis in polycythemia vera is associated with disease evolution but not thrombosis
Ronner L, Podoltsev N, Gotlib J, Heaney ML, Kuykendall AT, O’Connell C, Shammo J, Fleischman AG, Scherber RM, Mesa R, Yacoub A, Perkins C, Meckstroth S, Behlman L, Chiaramonte M, Salehi M, Ziadkhanpour K, Nguyen H, Siwoski O, Hung AK, Janania Martinez M, Nguyen J, Patel S, Kollipara R, Dave A, Randall M, Grant M, Harrison M, Fernandez Soto P, Tremblay D, Hoffman R, Moshier E, Mascarenhas J. Persistent leukocytosis in polycythemia vera is associated with disease evolution but not thrombosis. Blood 2020, 135: 1696-1703. PMID: 32107559, PMCID: PMC7205813, DOI: 10.1182/blood.2019003347.Peer-Reviewed Original ResearchClinical outcomes and characteristics of patients with TP53-mutated acute myeloid leukemia or myelodysplastic syndromes: a single center experience*
Bewersdorf JP, Shallis RM, Gowda L, Wei W, Hager K, Isufi I, Kim TK, Pillai MM, Seropian S, Podoltsev NA, Gore SD, Siddon AJ, Zeidan AM. Clinical outcomes and characteristics of patients with TP53-mutated acute myeloid leukemia or myelodysplastic syndromes: a single center experience*. Leukemia & Lymphoma 2020, 61: 2180-2190. PMID: 32362171, PMCID: PMC7603787, DOI: 10.1080/10428194.2020.1759051.Peer-Reviewed Original ResearchMeSH KeywordsHumansLeukemia, Myeloid, AcuteMutationMyelodysplastic SyndromesRetrospective StudiesTumor Suppressor Protein p53ConceptsAcute myeloid leukemiaMedian overall survivalTherapy-related malignanciesOverall survivalMyelodysplastic syndromeMyeloid leukemiaAllogeneic hematopoietic stem cell transplantLonger median overall survivalSingle-center retrospective studyComplex karyotypeHematopoietic stem cell transplantIntensive chemotherapy approachesYale Cancer CenterCharacteristics of patientsSingle-center experienceMinority of patientsStem cell transplantLong-term survivalLow response rateIntensive chemotherapyCenter experienceClinicopathologic characteristicsAdverse prognosisAML patientsCell transplantCui bono? Finding the value of allogeneic stem cell transplantation for lower-risk myelodysplastic syndromes
Shallis RM, Podoltsev NA, Gowda L, Zeidan AM, Gore SD. Cui bono? Finding the value of allogeneic stem cell transplantation for lower-risk myelodysplastic syndromes. Expert Review Of Hematology 2020, 13: 447-460. PMID: 32182435, DOI: 10.1080/17474086.2020.1744433.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAllograftsHematopoietic Stem Cell TransplantationHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesRisk AssessmentConceptsAllogeneic stem cell transplantationStem cell transplantationAcute myeloid leukemiaMyelodysplastic syndromeMDS patientsRisk stratificationCell transplantationPrognostic toolLower-risk myelodysplastic syndromesHigh-risk myelodysplastic syndromeLow-risk MDS patientsSevere bone marrow failureLow-risk diseaseLow-risk patientsOnly curative optionPrognosis of patientsBone marrow failureAggressive therapyCurative optionPrognostic impactEtiologic roleDisease progressionMyeloid leukemiaAlloSCTPatients
2019
Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study†
Davidoff AJ, Hu X, Bewersdorf JP, Wang R, Podoltsev NA, Huntington SF, Gore SD, Ma X, Zeidan AM. Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study†. Leukemia & Lymphoma 2019, 61: 1178-1187. PMID: 31878809, PMCID: PMC7735409, DOI: 10.1080/10428194.2019.1703970.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnemia, Refractory, with Excess of BlastsAzacitidineHumansMedicareMyelodysplastic SyndromesPropensity ScoreRetrospective StudiesUnited StatesConceptsHigh-risk myelodysplastic syndromeExcess blastsRefractory anemiaOverall survival benefitRetrospective cohort studyMedian OSOS benefitRAEB patientsCohort studySurvival benefitTherapy useMyelodysplastic syndromeClinical trialsLower riskMedicare dataPatientsPropensity scoreOlder adultsDiagnosisAnemiaQuartileUnited StatesAssociationEnd resultOSAssociation of provider experience and clinical outcomes in patients with myelodysplastic syndromes receiving hypomethylating agents
Zeidan AM, Hu X, Zhu W, Stahl M, Wang R, Huntington SF, Giri S, Bewersdorf JP, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. Association of provider experience and clinical outcomes in patients with myelodysplastic syndromes receiving hypomethylating agents. Leukemia & Lymphoma 2019, 61: 397-408. PMID: 31570040, PMCID: PMC7732188, DOI: 10.1080/10428194.2019.1663423.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntimetabolites, AntineoplasticHumansMedicareMyelodysplastic SyndromesProportional Hazards ModelsUnited StatesConceptsMyelodysplastic syndromeOverall survivalHMA cyclesHMA therapyProvider experienceCox proportional hazards modelOlder MDS patientsMedian overall survivalPercent of patientsSEER-Medicare dataMultivariate logistic regressionProportional hazards modelHMA initiationClinical outcomesMDS patientsClinical trialsMedian numberHMA treatmentHazards modelPatientsSignificant associationLogistic regressionPopulation-level survivalSurvivalSyndromeRBC transfusion independence among lower risk MDS patients receiving hypomethylating agents: a population-level analysis
Zeidan AM, Zhu W, Stahl M, Wang R, Huntington SF, Giri S, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. RBC transfusion independence among lower risk MDS patients receiving hypomethylating agents: a population-level analysis. Leukemia & Lymphoma 2019, 60: 3181-3187. PMID: 31170846, DOI: 10.1080/10428194.2019.1622700.Peer-Reviewed Original ResearchConceptsRBC transfusion independenceLR-MDS patientsTransfusion independenceHMA initiationRBC transfusionClinical effectivenessReal-life clinical effectivenessRed blood cell transfusionLower-risk myelodysplastic syndromesLow-risk MDS patientsRisk MDS patientsBlood cell transfusionRisk myelodysplastic syndromesHMA therapyLR-MDSCell transfusionMost patientsDisease courseMDS patientsMedicare databaseMyelodysplastic syndromePopulation-level estimatesLower oddsTransfusionPatientsGuadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial
Garcia-Manero G, Roboz G, Walsh K, Kantarjian H, Ritchie E, Kropf P, O'Connell C, Tibes R, Lunin S, Rosenblat T, Yee K, Stock W, Griffiths E, Mace J, Podoltsev N, Berdeja J, Jabbour E, Issa JJ, Hao Y, Keer HN, Azab M, Savona MR. Guadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial. The Lancet Haematology 2019, 6: e317-e327. PMID: 31060979, PMCID: PMC9012213, DOI: 10.1016/s2352-3026(19)30029-8.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeMyelodysplastic syndromeRefractory cohortAdverse eventsRefractory diseaseHypomethylating agentEastern Cooperative Oncology Group performance statusNorth American medical centersInternational Prognostic Scoring SystemCommon grade 3Phase 2 partWorse adverse eventsOpen-label studyProportion of patientsPrognostic scoring systemOverall responseChronic myelomonocytic leukemiaNew therapeutic optionsAmerican medical centersEligible patientsFebrile neutropaeniaIntravenous decitabinePrimary endpointRefractory patientsStudy drugA highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies
Song Y, Rongvaux A, Taylor A, Jiang T, Tebaldi T, Balasubramanian K, Bagale A, Terzi YK, Gbyli R, Wang X, Fu X, Gao Y, Zhao J, Podoltsev N, Xu M, Neparidze N, Wong E, Torres R, Bruscia EM, Kluger Y, Manz MG, Flavell RA, Halene S. A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies. Nature Communications 2019, 10: 366. PMID: 30664659, PMCID: PMC6341122, DOI: 10.1038/s41467-018-08166-x.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsMyelodysplastic syndromeXenotransplantation modelDysplastic morphologyImmunodeficient murine hostsPre-clinical studiesMDS stem cellsMDS subtypesComprehensive preclinical studiesPreclinical studiesTherapeutic efficacyMurine hostSerial transplantationDrug mechanismsMDS researchStem cell propagationStem cellsDifferentiation potentialHematopoietic stem cell nicheGenetic complexityNovel avenuesStem cell nicheCell propagationDisease representationsImmunodeficient
2018
Be careful of the masquerades: differentiating secondary myelodysplasia from myelodysplastic syndromes in clinical practice
Shallis RM, Xu ML, Podoltsev NA, Curtis SA, Considine BT, Khanna SR, Siddon AJ, Zeidan AM. Be careful of the masquerades: differentiating secondary myelodysplasia from myelodysplastic syndromes in clinical practice. Annals Of Hematology 2018, 97: 2333-2343. PMID: 30109425, DOI: 10.1007/s00277-018-3474-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdultDiagnosis, DifferentialFemaleHematologic NeoplasmsHumansMaleMiddle AgedMyelodysplastic SyndromesConceptsMyelodysplastic syndromeSecondary myelodysplasiaSecondary causesAllogeneic hematopoietic cell transplantationDiagnosis of MDSRepresentative case seriesUnderlying myelodysplastic syndromeHematopoietic cell transplantationLack of efficacyHematologists/oncologistsMeticulous exclusionResultant cytopeniasIntensive chemotherapyCase seriesMorphologic reviewCell transplantationDiagnostic dilemmaSuch therapyMalignant processExpert hematopathologistsClinical practiceMyelodysplasiaCytogenetic abnormalitiesPatientsSpecialized physiciansThe use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort
Stahl M, DeVeaux M, de Witte T, Neukirchen J, Sekeres MA, Brunner AM, Roboz GJ, Steensma DP, Bhatt VR, Platzbecker U, Cluzeau T, Prata PH, Itzykson R, Fenaux P, Fathi AT, Smith A, Germing U, Ritchie EK, Verma V, Nazha A, Maciejewski JP, Podoltsev NA, Prebet T, Santini V, Gore SD, Komrokji RS, Zeidan AM. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort. Blood Advances 2018, 2: 1765-1772. PMID: 30037803, PMCID: PMC6058241, DOI: 10.1182/bloodadvances.2018019414.Peer-Reviewed Original ResearchConceptsAnti-thymocyte globulinRBC transfusion independenceImmunosuppressive therapyTransfusion independenceOverall response rateHypocellular bone marrowMyelodysplastic syndromeOverall survivalBone marrowRed blood cell transfusion independenceHorse anti-thymocyte globulinRabbit anti-thymocyte globulinInternational Working Group criteriaCox proportional hazards modelSingle-center natureMedian overall survivalKaplan-Meier methodLarge international cohortLarge international patient cohortProportional hazards modelInternational patient cohortPredictors of benefitParoxysmal nocturnal hemoglobinuriaLogistic regression modelsSteroid monotherapyCounseling patients with higher-risk MDS regarding survival with azacitidine therapy: are we using realistic estimates?
Zeidan AM, Stahl M, DeVeaux M, Giri S, Huntington S, Podoltsev N, Wang R, Ma X, Davidoff AJ, Gore SD. Counseling patients with higher-risk MDS regarding survival with azacitidine therapy: are we using realistic estimates? Blood Cancer Journal 2018, 8: 55. PMID: 29891916, PMCID: PMC5995881, DOI: 10.1038/s41408-018-0081-8.Peer-Reviewed Original Research
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
2016
Comparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes
Zeidan AM, Davidoff AJ, Long JB, Hu X, Wang R, Ma X, Gross CP, Abel GA, Huntington SF, Podoltsev NA, Hajime U, Prebet T, Gore SD. Comparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes. British Journal Of Haematology 2016, 175: 829-840. PMID: 27650975, DOI: 10.1111/bjh.14305.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromeRAEB patientsMedian survivalClinical trialsMultivariate Cox proportional hazards modelCox proportional hazards modelKaplan-Meier methodPopulation-based survivalSignificant survival differenceComparative clinical effectivenessProportional hazards modelAgent azacitidineHMA initiationExcess blastsOlder patientsRandomized trialsHistological subtypesRefractory anemiaClinical effectivenessSurvival differencesSubset analysisSurvival advantageHazards modelPatientsDecitabine
2015
The clinical use of DNA methyltransferase inhibitors in myelodysplastic syndromes
Zahr A, Aldin E, Barbarotta L, Podoltsev N, Zeidan AM. The clinical use of DNA methyltransferase inhibitors in myelodysplastic syndromes. Expert Review Of Anticancer Therapy 2015, 15: 1019-1036. PMID: 26292903, DOI: 10.1586/14737140.2015.1061936.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsDisease ProgressionDNA (Cytosine-5-)-MethyltransferasesEnzyme InhibitorsEpigenesis, GeneticHumansMyelodysplastic SyndromesSurvival RateConceptsHigh-risk myelodysplastic syndromeRisk myelodysplastic syndromesMyelodysplastic syndromeDNA methyltransferase inhibitorClinical useAllogeneic hematopoietic cell transplantationHematopoietic cell transplantationAcute myeloid leukemiaMethyltransferase inhibitorFull therapeutic potentialOverall survivalPeripheral cytopeniasCurative treatmentCell transplantationDismal outcomeTreatment optionsMyeloid leukemiaIneffective hematopoiesisOnly interventionTherapeutic potentialHematopoietic malignanciesHeterogeneous groupPatientsSyndromeInhibitors