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, 65: 1541-1551. 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’ 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 outcomeTreatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Kewan T, Stahl M, Bewersdorf J, Zeidan A. Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. Current Hematologic Malignancy Reports 2024, 19: 138-150. PMID: 38632155, DOI: 10.1007/s11899-024-00733-y.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationLower-risk MDSErythropoiesis-stimulating agentsHypomethylating agentsIPSS-MHR-MDSRisk stratificationMolecular International Prognostic Scoring SystemRisk of leukemia progressionTreated with hypomethylating agentsInternational Prognostic Scoring SystemTreatment of myelodysplastic syndromesOral hypomethylating agentsHigh-risk MDSPrognostic Scoring SystemStem cell transplantationEnhanced risk stratificationRecent FindingsRecent advancesRefine treatment strategiesQuality-of-life improvementAssociated with treatmentTreatment decision-makingIntensive chemotherapyMDS patientsHypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML
Shimony S, Bewersdorf J, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos Perez J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML. Leukemia 2024, 38: 762-768. PMID: 38378841, DOI: 10.1038/s41375-024-02175-0.Peer-Reviewed Original ResearchAssociated with improved OSHypomethylating agentsCPX-351Overall survivalSplicing factor mutationsCo-mutationsAllogeneic hematopoietic stem cell transplantationAssociated with better OSAssociated with worse OSSecondary acute myeloid leukemiaHematopoietic stem cell transplantationMedian overall survivalStem cell transplantationPatients aged >Acute myeloid leukemiaTreated with daunorubicinLiposomal daunorubicinMonosomal karyotypeNRAS/KRAS mutationsImproved OSSecondary AMLMyeloid diseasesMyeloid neoplasmsAML patientsAML treatment
2023
Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Underwent Allogenic Stem Cell Transplantation (HSCT)
Kewan T, Bewersdorf J, Blaha O, Stahl M, Al Ali N, DeZern A, Sekeres M, Uy G, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, Amaya M, Zeidner J, Savona M, Stempel J, Chandhok N, Logothetis C, Cochran H, Rose A, Roboz G, Wang E, Rolles B, Harris A, Shallis R, Xie Z, Padron E, Maciejewski J, Sallman D, Della Porta M, Komrokji R, Zeidan A. Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Underwent Allogenic Stem Cell Transplantation (HSCT). Blood 2023, 142: 4980. DOI: 10.1182/blood-2023-186578.Peer-Reviewed Original ResearchOverall survivalHigh-risk groupUnderwent HSCTC-indexRisk groupsHigh riskDonor typeInternational Prognostic Scoring SystemAllogenic stem cell transplantationTime of HSCTMedian overall survivalReduced-intensity conditioningSignificant OS differencePrognostic scoring systemRisk stratification toolTime of diagnosisStem cell transplantationSingle-institution analysisLog-rank testHarrell's C-indexDifferent overall survivalCox proportional hazardsHMA cyclesHaploidentical donorsMaintenance therapyClinical 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 pointsIntensive Induction Chemotherapy (IC) Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in IDH1- or IDH2-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 (IC) Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in IDH1- or IDH2-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study. Blood 2023, 142: 1589. DOI: 10.1182/blood-2023-174283.Peer-Reviewed Original ResearchIntensive induction chemotherapyAcute myeloid leukemiaComposite complete responseMedian overall survivalOverall survivalComplete responseIDH2 mutationsAllo-SCTLarge multicenter retrospective cohort studyMulticenter retrospective cohort studyAllogeneic stem cell transplantationSecondary acute myeloid leukemiaComparable overall survivalIDH1 inhibitor ivosidenibHigh rateRetrospective cohort studyStem cell transplantationLog-rank testStandard of careLarge academic centerYears of ageEffect of treatmentIDH-mutant AMLMultivariable stepwiseFit patientsWhat Is the Optimal Treatment Modality in Molecularly Defined Secondary AML? a Multicenter Cohort Study
Shimony S, Bewersdorf J, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Chen E, Ramos J, Lindsley R, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. What Is the Optimal Treatment Modality in Molecularly Defined Secondary AML? a Multicenter Cohort Study. Blood 2023, 142: 1478. DOI: 10.1182/blood-2023-172763.Peer-Reviewed Original ResearchAcute myeloid leukemiaComposite complete responseStem cell transplantationOverall survivalCPX-351Complete responseTreatment modalitiesMonosomal karyotypeCohort studyOdds ratioTreatment groupsLarge multicenter retrospective cohort studyMulticenter retrospective cohort studyAllogeneic stem cell transplantationSecondary acute myeloid leukemiaIncomplete count recoveryImproved overall survivalMedian overall survivalMulticenter cohort studyRetrospective cohort studyWorse overall survivalOptimal treatment modalityOptimal treatment selectionLog-rank testEffect of treatmentIntensive 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 exposureOral 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
Are 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 subsetsPatientsPrognosisLeukemiaTreatment Utilization and Characteristics Among Patients with Higher-Risk Myelodysplastic Syndromes According to Hypomethylating Agent Use
Zeidan A, Divino V, DeKoven M, Shah D, Wang E, Bey D, Salimi T, Epstein R. Treatment Utilization and Characteristics Among Patients with Higher-Risk Myelodysplastic Syndromes According to Hypomethylating Agent Use. Blood 2021, 138: 5030. DOI: 10.1182/blood-2021-144852.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeHigher comorbidity burdenHMA therapySupportive careTrials CommitteeComorbidity burdenTreatment utilizationMean ageMyelodysplastic syndromeReal-world clinical practiceBaseline renal diseaseIntra-Cellular TherapiesLower comorbidity burdenAbsence of progressionRetrospective observational studyStem cell transplantationSimilar mean ageReal-world studyCurrent employmentFrailer patientsIQVIA PharMetricsSubcutaneous azacitidineIndex dateIntensive chemotherapy
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 agent