2024
A review of the isocitrate dehydrogenase inhibitors in management of adult patients with AML and MDS
Norman M, Yamartino K, Gerstein R, Shallis R, Mendez L, Podoltsev N, Stahl M, Eighmy W, Zeidan A. A review of the isocitrate dehydrogenase inhibitors in management of adult patients with AML and MDS. Expert Review Of Hematology 2024, 17: 755-767. PMID: 39474840, DOI: 10.1080/17474086.2024.2422554.Peer-Reviewed Original ResearchDiagnosed AMLSurvival benefitManagement of acute myeloid leukemiaDevelopment of oral therapiesIsocitrate dehydrogenase inhibitorsNewly diagnosed AMLManagement of adult patientsPost-transplant maintenanceAcute myeloid leukemiaSingle-arm studyExcellent response ratesIDH inhibitorsRelapsed AMLHypomethylating agentsInhibitor therapyMyelodysplastic syndromeOral therapyCombination therapyPost-transplantMyeloid leukemiaImproved survivalSingle-armAdult patientsAzacitidineRandomized studyImmune Landscape and Outcomes of Patients with RNA Splicing Factor-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes Treated with Azacitidine +/- the Anti-PD-L1 Antibody Durvalumab
Bewersdorf J, Hasle V, Shallis R, Thompson E, De Menezes D, Rose S, Boss I, Mendez L, Podoltsev N, Stahl M, Kewan T, Halene S, Haferlach T, Fox B, Zeidan A. Immune Landscape and Outcomes of Patients with RNA Splicing Factor-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes Treated with Azacitidine +/- the Anti-PD-L1 Antibody Durvalumab. Blood 2024, 144: 4585. DOI: 10.1182/blood-2024-194929.Peer-Reviewed Original ResearchAcute myeloid leukemiaAnti-PD-L1 antibody durvalumabOverall response rateMyelodysplastic syndromeComplete responseBM aspiratesMyeloid leukemiaInternational Working GroupBone marrowMyelodysplastic syndromes treated with azacitidineAcute myeloid leukemia ptsWild-type acute myeloid leukemiaSecondary acute myeloid leukemiaResponse criteriaAnti-PD-L1Immune checkpoint inhibitorsTreated with azacitidineOutcomes of patientsAny-cause deathGeneration of neoantigensVariant allele frequencySusceptible to treatmentMarrow CRAdverse cytogeneticsCheckpoint inhibitorsThe 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 featuresClinical Utilization and Outcomes of Hypomethylating Agents and Venetoclax in Patients with Myelodysplastic Syndrome - a Multicenter Retrospective Analysis
Guru Murthy G, Ball S, Feld J, Abboud R, Haddadin M, Patel S, Kishtagari A, Hawkins H, Guerra V, Dworkin E, Tawfiq R, Dulak D, Feng A, Cotte C, Cohen-Nowak A, Shukla A, Balasubramanian S, Winer E, Foucar C, Abaza Y, Shallis R, Lin C, Badar T, Patel A, Im A, Szabo A, Atallah E. Clinical Utilization and Outcomes of Hypomethylating Agents and Venetoclax in Patients with Myelodysplastic Syndrome - a Multicenter Retrospective Analysis. Blood 2024, 144: 3206-3206. DOI: 10.1182/blood-2024-211623.Peer-Reviewed Original ResearchHMA monotherapyTumor lysis syndromePhase 3 randomized clinical trialEvent free survivalHypomethylating agentsMulticenter retrospective analysisMyelodysplastic syndromeAdverse eventsUS academic medical centersClinical trialsUpfront settingFree survivalOverall survivalClinical outcomesRetrospective analysisClinical management of myelodysplastic syndromesIncidence of tumor lysis syndromeAcademic medical centerManagement of myelodysplastic syndromesAllogeneic stem cell transplantationSingle arm clinical trialResponse rateOutpatient settingStem cell transplantationMedical CenterPrognostic 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 S, 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 outcomeIntegrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Integrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine. Therapeutic Advances In Hematology 2024, 15: 20406207241257904. PMID: 38883163, PMCID: PMC11180421, DOI: 10.1177/20406207241257904.Peer-Reviewed Original ResearchHigher-risk myelodysplastic syndromesAcute myeloid leukemiaBone marrowMutation statusImmune landscapeImmunological landscapeAnti-PD-L1 antibody durvalumabHR-MDS patientsWild-type acute myeloid leukemiaTP53-mutant acute myeloid leukemiaMutant acute myeloid leukemiaAzacitidine-based therapyWild-type patientsImmune checkpoint proteinsImmune checkpoint expressionT cell populationsWild-typeStatistically significant decreaseAZA therapyImmunosuppressive microenvironmentPD-L1Mutant patientsDNA methylation arraysCheckpoint expressionMyelodysplastic syndrome
2023
Characteristics and Outcomes of Younger Adult Patients (Pts) with Myelodysplastic Syndromes (MDS): A Multicenter Retrospective Study
Abaza Y, Xie Z, Burkart M, Badar T, Desai P, Shallis R, Patel A, Cohen-Nowak A, Oh T, Walker C, Easwar N, Kewan T, Cannova J, Bell-Burdett K, Al Ali N, Sallman D, Roboz G, Carraway H, Zeidan A, Patnaik M, Altman J, Komrokji R. Characteristics and Outcomes of Younger Adult Patients (Pts) with Myelodysplastic Syndromes (MDS): A Multicenter Retrospective Study. Blood 2023, 142: 3232. DOI: 10.1182/blood-2023-188328.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeMedian overall survivalMulticenter retrospective studyRisk myelodysplastic syndromesOverall survivalYA groupMyelodysplastic syndromeYounger ptsComplete remissionAllo-SCTBaseline characteristicsFrontline therapyHematologic improvementMedian ageRetrospective studyCommon subtypeBlasts-2Exact testUpfront allogeneic stem cell transplantationIntermediate-risk myelodysplastic syndromesTherapy-related myelodysplastic syndromeAllogeneic stem cell transplantationDe novo myelodysplastic syndromeExcess blasts-2Marrow complete remissionIntensive 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 exposureSecond 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
2022
Agent Orange and dioxin-induced myeloid leukemia: a weaponized vehicle of leukemogenesis
Shallis RM, Gore SD. Agent Orange and dioxin-induced myeloid leukemia: a weaponized vehicle of leukemogenesis. Leukemia & Lymphoma 2022, 63: 1534-1543. PMID: 35105250, DOI: 10.1080/10428194.2022.2034156.Peer-Reviewed Original ResearchNCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 3.2022.
Greenberg PL, Stone RM, Al-Kali A, Bennett JM, Borate U, Brunner AM, Chai-Ho W, Curtin P, de Castro CM, Deeg HJ, DeZern AE, Dinner S, Foucar C, Gaensler K, Garcia-Manero G, Griffiths EA, Head D, Jonas BA, Keel S, Madanat Y, Maness LJ, Mangan J, McCurdy S, McMahon C, Patel B, Reddy VV, Sallman DA, Shallis R, Shami PJ, Thota S, Varshavsky-Yanovsky AN, Westervelt P, Hollinger E, Shead DA, Hochstetler C. NCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 3.2022. Journal Of The National Comprehensive Cancer Network 2022, 20: 106-117. PMID: 35130502, DOI: 10.6004/jnccn.2022.0009.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromeNCCN guidelinesHigh-risk myelodysplastic syndromeNCCN Guidelines InsightsSupportive care recommendationsManagement of patientsClinical evidencePrognostic significanceTreatment recommendationsCare recommendationsMultidisciplinary panelHigh-risk assessmentPredisposition syndromeBiologic factorsSyndromeMDS expertsGuidelinesImportant advancesPatientsRecommendationsTherapyDiagnosis
2021
Management of the Older Patient with Myelodysplastic Syndrome
Shallis RM, Zeidan AM. Management of the Older Patient with Myelodysplastic Syndrome. Drugs & Aging 2021, 38: 751-767. PMID: 34342860, DOI: 10.1007/s40266-021-00881-3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeOlder patientsAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationPrevalence of frailtyMajority of patientsStem cell transplantationPatient-specific factorsDrug-drug interactionsQuality of lifeAbsolute contraindicationPalliative therapyCare therapyCurative therapyIntensive therapyCell transplantationOptimal treatmentSubgroup analysisPatientsPsychosocial issuesSyndromeTherapyPersonalized treatmentAge associatesOlder populationPeri‐transfusion quality‐of‐life assessment for patients with myelodysplastic syndromes
Abel GA, Klepin HD, Magnavita ES, Jaung T, Lu W, Shallis RM, Hantel A, Bahl NE, Dellinger‐Johnson R, Winer ES, Zeidan AM. Peri‐transfusion quality‐of‐life assessment for patients with myelodysplastic syndromes. Transfusion 2021, 61: 2830-2836. PMID: 34251040, DOI: 10.1111/trf.16584.Peer-Reviewed Original ResearchConceptsRed cell transfusionCell transfusionMyelodysplastic syndromeFollow-up questionnaireTransfusion decisionsQoL assessmentProportion of patientsProspective pilot studyQoL 1Repeat transfusionHemoglobin levelsPatients' qualityScore 7TransfusionPatientsStudy designQoLPilot studySignificant increaseSyndromeLife assessmentSignificant changesDaysQuestionnaireAssessmentClinical and Molecular Approach to Adult-Onset, Neoplastic Monocytosis
Shallis RM, Siddon AJ, Zeidan AM. Clinical and Molecular Approach to Adult-Onset, Neoplastic Monocytosis. Current Hematologic Malignancy Reports 2021, 16: 276-285. PMID: 33890194, DOI: 10.1007/s11899-021-00632-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPersistent monocytosisAppropriate diagnosisMyelomonocytic leukemiaPCM1-JAK2 fusionChronic myelomonocytic leukemiaAcute myeloid leukemiaAcute myelomonocytic leukemiaNegative predictive valuePurpose of ReviewInMyelodysplastic syndromeReactive monocytosisFGFR1 rearrangementAdult onsetMyeloid leukemiaMonocytosisBCR-ABL1Predictive valueASXL1 mutationsMyeloproliferative neoplasmsDiagnostic approachCytometric analysisMarrow tissuesLeukemiaDiagnosisMonocytic differentiation
2020
Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways
Bewersdorf JP, Shallis RM, Zeidan AM. Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways. Blood Reviews 2020, 45: 100709. PMID: 32487480, DOI: 10.1016/j.blre.2020.100709.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsMyeloid malignanciesPD-1/PD-L1CTLA-4 pathwayImmune checkpoint inhibitionAcute myeloid leukemiaSafe combination therapyICI therapyImmunologic landscapeCheckpoint inhibitorsDisease coursePD-L1Checkpoint inhibitionMyelodysplastic syndromeCombination therapyMechanisms of resistanceClinical trialsMyeloid leukemiaClinical developmentPotential biomarkersNovel targetPatientsMalignancyTherapyBiomarkersClinical 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 ResearchConceptsAcute 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 StatementsConceptsAllogeneic 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
Getting personal with myelodysplastic syndromes: is now the right time?
Chokr N, Pine AB, Bewersdorf JP, Shallis RM, Stahl M, Zeidan AM. Getting personal with myelodysplastic syndromes: is now the right time? Expert Review Of Hematology 2019, 12: 215-224. PMID: 30977414, PMCID: PMC6540985, DOI: 10.1080/17474086.2019.1592673.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeNext-generation sequencingTherapy selectionPrognosis of MDSRole of NGSPrognosis of patientsRoutine clinical practiceMinimal residual diseaseRecurrent genetic abnormalitiesResidual diseaseBlood countDisease stagePeripheral bloodHematologic malignanciesPrognostic evaluationMDS pathogenesisRoutine managementTherapy decisionsHealthy individualsBone marrowClinical practiceCytological examinationPatientsScoring systemDiagnostic accuracy
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 improvementImmunosuppressive therapy in myelodysplastic syndromes: a borrowed therapy in search of the right place
Shallis RM, Chokr N, Stahl M, Pine AB, Zeidan AM. Immunosuppressive therapy in myelodysplastic syndromes: a borrowed therapy in search of the right place. Expert Review Of Hematology 2018, 11: 715-726. PMID: 30024293, DOI: 10.1080/17474086.2018.1503049.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmunosuppressive therapyMyelodysplastic syndromeImmune pathwaysManagement of MDSTreatment of MDSClonal hematopoietic stem cell disordersMeaningful clinical activityAdaptive immune pathwaysHematopoietic stem cell disordersStem cell disordersImmune dysregulationDisease coursePeripheral cytopeniasClinical benefitImmune activationTherapeutic optionsAplastic anemiaClinical activityHematologic diseasesCell disordersClinical experienceContinued clarificationLeukemic progressionTherapyPatients