2021
Preliminary Safety and Efficacy Results from Precizn-1: An Ongoing Phase 1/2 Study on Zinc Finger Nuclease-Modified Autologous CD34+ HSPCs for Sickle Cell Disease (SCD)
Alavi A, Krishnamurti L, Abedi M, Galeon I, Reiner D, Smith S, Wang L, Ramezi A, Rendo P, Walters M. Preliminary Safety and Efficacy Results from Precizn-1: An Ongoing Phase 1/2 Study on Zinc Finger Nuclease-Modified Autologous CD34+ HSPCs for Sickle Cell Disease (SCD). Blood 2021, 138: 2930. DOI: 10.1182/blood-2021-151650.Peer-Reviewed Original ResearchSickle cell diseaseVaso-occlusive crisisAdverse eventsAutologous CD34Apheresis cyclesWeek 26Cell diseaseSpeakers bureauTotal HbOngoing phase 1/2 studySevere sickle cell diseaseF cellsPhase 1/2 studyBaseline patient characteristicsRelated adverse eventsHealth-related qualityPeripheral blood WBCCurrent unmet needPotential therapeutic valueEarly termination visitMinimum cell doseStem cell engraftmentTrend of improvementCurrent employmentElevated fetal hemoglobin
2020
Resolution of Serious Vaso-Occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy
Thompson A, Walters M, Mapara M, Kwiatkowski J, Krishnamurti L, Aygun B, Kasow K, Rifkin-Zenenberg S, Schmidt M, DelCarpini J, Pierciey F, Miller A, Gallagher M, Chen R, Goyal S, Kanter J, Tisdale J. Resolution of Serious Vaso-Occlusive Pain Crises and Reduction in Patient-Reported Pain Intensity: Results from the Ongoing Phase 1/2 HGB-206 Group C Study of LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy. Blood 2020, 136: 16-17. DOI: 10.1182/blood-2020-134940.Peer-Reviewed Original ResearchAcute chest syndromeVaso-occlusive crisisSickle cell diseaseVaso-occlusive eventsPain intensity scoresGroup C patientsAdverse eventsPain intensityBluebird BioC patientsLast visitBusulfan conditioningHemolysis markersTotal HbIntensity scoresAcute vaso-occlusive painBackground Sickle cell diseasePathophysiology of SCDVaso-occlusive pain crisesPopulation normsPatient-reported pain intensityAdvisory CommitteeGene therapy×109/LAbnormal sickle hemoglobinSafety of Autologous Hematopoietic Stem Cell Transplantation with Gene Addition Therapy for Transfusion-Dependent β-Thalassemia, Sickle Cell Disease, and Cerebral Adrenoleukodystrophy
Walters M, Locatelli F, Thrasher A, Tisdale J, Orchard P, Duncan C, Kühl J, De Oliveira S, Sauer M, Kulozik A, Yannaki E, Hongeng S, Mapara M, Krishnamurti L, Hermine O, Blanche S, Aubourg P, Smith N, Shi W, Colvin R, McNeil E, Ribeil J, Cavazzana M, Williams D. Safety of Autologous Hematopoietic Stem Cell Transplantation with Gene Addition Therapy for Transfusion-Dependent β-Thalassemia, Sickle Cell Disease, and Cerebral Adrenoleukodystrophy. Transplantation And Cellular Therapy 2020, 26: s38-s39. DOI: 10.1016/j.bbmt.2019.12.104.Peer-Reviewed Original ResearchTransfusion-dependent β-thalassemiaSickle cell diseaseHematopoietic stem cell transplantationCerebral adrenoleukodystrophyStem cell transplantationAdverse eventsAllo-HSCTSafety profileCell transplantationCell diseaseAllogeneic hematopoietic stem cell transplantationAutologous hematopoietic stem cell transplantationGene addition therapyLentiviral vectorsBusulfan/cyclophosphamideCommon adverse eventsSecondary graft failureRisk of GVHDLong-term followRisk of complicationsΒ-thalassemiaImproved safety profileDP infusionFebrile neutropeniaAutologous HSCTLentiglobin for Sickle Cell Disease (SCD) Gene Therapy (GT): Updated Results in Group C Patients from the Phase 1/2 Hgb-206 Study
Walters M, Kanter J, Kwiatkowski J, Krishnamurti L, Mapara M, Schmidt M, Miller A, Pierciey F, Bonner M, Huang W, Ribeil J, Thompson A, Tisdale J. Lentiglobin for Sickle Cell Disease (SCD) Gene Therapy (GT): Updated Results in Group C Patients from the Phase 1/2 Hgb-206 Study. Transplantation And Cellular Therapy 2020, 26: s1-s2. DOI: 10.1016/j.bbmt.2019.12.136.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsGroup C patientsAdverse eventsC patientsMedian HbTotal HbPlerixafor mobilizationNon-hematologic gradeGene therapySerious adverse eventsBlood mononuclear cellsLentiviral vectorsStrong therapeutic benefitFebrile neutropeniaSevere SCDConclusions PatientsGraft failureInitial patientsLast visitMononuclear cellsBusulfan conditioningHemolysis markersAutologous CD34Colony-forming unit assaysTherapeutic benefit
2019
Exploring the Drivers of Potential Clinical Benefit in Initial Patients Treated in the Hgb-206 Study of Lentiglobin for Sickle Cell Disease (SCD) Gene Therapy
Walters M, Tisdale J, Kwiatkowski J, Krishnamurti L, Mapara M, Schmidt M, Miller A, Pierciey F, Huang W, Ribeil J, Kanter J, Thompson A. Exploring the Drivers of Potential Clinical Benefit in Initial Patients Treated in the Hgb-206 Study of Lentiglobin for Sickle Cell Disease (SCD) Gene Therapy. Blood 2019, 134: 2061. DOI: 10.1182/blood-2019-128814.Peer-Reviewed Original ResearchAcute chest syndromeVaso-occlusive crisisGroup A patientsRate of VOCAdverse eventsA patientsPatient 1Group AClinical benefitLast visitBluebird BioHematopoietic stem cellsInitial patientsPatient 2Busulfan conditioningGroup BHbF levelsVeno-occlusive liver diseaseRed blood cell transfusionFull hematological recoveryBlood cell transfusionCases of gradeLentiviral vectorsGene therapyPotential clinical benefitResolution of Sickle Cell Disease Manifestations in Patients Treated with Lentiglobin Gene Therapy: Updated Results from the Phase 1/2 Hgb-206 Group C Study
Kanter J, Tisdale J, Mapara M, Kwiatkowski J, Krishnamurti L, Schmidt M, Miller A, Pierciey F, Huang W, Ribeil J, Thompson A, Walters M. Resolution of Sickle Cell Disease Manifestations in Patients Treated with Lentiglobin Gene Therapy: Updated Results from the Phase 1/2 Hgb-206 Group C Study. Blood 2019, 134: 990. DOI: 10.1182/blood-2019-128894.Peer-Reviewed Original ResearchGroup C patientsRed blood cell transfusionBlood cell transfusionAdverse eventsC patientsMedian Hb levelHb levelsBluebird BioHematopoietic stem cellsCell transfusionLast visitBusulfan conditioningTotal hemoglobinHSC collectionGene therapyNon-hematologic gradeSerious adverse eventsLentiviral vectorsSickle cell diseaseStrong therapeutic effectVector copy numberCancer Research CenterAdditional patient dataAdvisory CommitteeSevere SCDS1633 UPDATED RESULTS FROM THE HGB‐206 STUDY IN PATIENTS WITH SEVERE SICKLE CELL DISEASE TREATED UNDER A REVISED PROTOCOL WITH LENTIGLOBIN GENE THERAPY USING PLERIXAFOR‐MOBILISED HAEMATOPOIETIC STEM CELLS
Kanter J, Thompson A, Mapara M, Kwiatkowski J, Krishnamurti L, Schmidt M, Miller A, Pierciey F, Huang W, Ribeil J, Walters M, Tisdale J. S1633 UPDATED RESULTS FROM THE HGB‐206 STUDY IN PATIENTS WITH SEVERE SICKLE CELL DISEASE TREATED UNDER A REVISED PROTOCOL WITH LENTIGLOBIN GENE THERAPY USING PLERIXAFOR‐MOBILISED HAEMATOPOIETIC STEM CELLS. HemaSphere 2019, 3: 754-755. DOI: 10.1097/01.hs9.0000564780.30358.eb.Peer-Reviewed Original ResearchSickle cell diseaseSevere sickle cell diseaseGroup C patientsAdverse eventsHaematopoietic stem cellsLast visitGroup CDP infusionC patientsRBC transfusionMonth followHb levelsCell diseaseVeno-occlusive liver diseaseHSC collectionRed blood cell transfusionGene therapyX109/LBlood cell transfusionTotal HbVaso-occlusive eventsLentiviral vectorsInclusion of adolescentsStem cellsBusulfan levelsLentiglobin Gene Therapy in Patients with Sickle Cell Disease: Updated Interim Results from Hgb-206
Mapara M, Tisdale J, Kanter J, Kwiatkowski J, Krishnamurti L, Schmidt M, Miller A, Pierciey F, Shi W, Ribeil J, Asmal M, Thompson A, Walters M. Lentiglobin Gene Therapy in Patients with Sickle Cell Disease: Updated Interim Results from Hgb-206. Transplantation And Cellular Therapy 2019, 25: s64-s65. DOI: 10.1016/j.bbmt.2018.12.147.Peer-Reviewed Original ResearchSickle cell diseaseGrade 3 adverse eventsAdverse eventsHematopoietic stem cellsGrp BC patientsCell diseaseSevere sickle cell diseaseGene therapyNon-hematologic gradeVaso-occlusive painPhase 1 studyLentiviral vectorsAutologous hematopoietic stem cellsGrp CFebrile neutropeniaMyeloablative conditioningClinical effectsHb levelsLast visitBusulfan conditioningAutologous CD34Treatment characteristicsMethods AdultsPatients
2018
Outcomes for Initial Patient Cohorts with up to 33 Months of Follow-up in the Hgb-206 Phase 1 Trial
Kanter J, Tisdale J, Kwiatkowski J, Krishnamurti L, Mapara M, Schmidt M, Miller A, Pierciey F, Shi W, Ribeil J, Walters M, Thompson A. Outcomes for Initial Patient Cohorts with up to 33 Months of Follow-up in the Hgb-206 Phase 1 Trial. Blood 2018, 132: 1080. DOI: 10.1182/blood-2018-99-113477.Peer-Reviewed Original ResearchSevere sickle cell diseaseGroup B patientsSickle cell diseaseGroup A patientsB patientsAdverse eventsGroup ALast visitTotal bilirubinBluebird BioHematopoietic stem cellsA patientsPeripheral bloodBusulfan conditioningReticulocyte countTotal HbVeno-occlusive liver diseaseAdvisory CommitteeMedical directorsNormalization of HbVaso-occlusive painSerious adverse eventsLong-term followPhase 1 trialSignificant clinical benefitCurrent Results of Lentiglobin Gene Therapy in Patients with Severe Sickle Cell Disease Treated Under a Refined Protocol in the Phase 1 Hgb-206 Study
Tisdale J, Kanter J, Mapara M, Kwiatkowski J, Krishnamurti L, Schmidt M, Miller A, Pierciey F, Shi W, Ribeil J, Asmal M, Thompson A, Walters M. Current Results of Lentiglobin Gene Therapy in Patients with Severe Sickle Cell Disease Treated Under a Refined Protocol in the Phase 1 Hgb-206 Study. Blood 2018, 132: 1026. DOI: 10.1182/blood-2018-99-113480.Peer-Reviewed Original ResearchSevere sickle cell diseaseSickle cell diseaseNon-cardiac chest painVaso-occlusive painAdverse eventsHb levelsBluebird BioHematopoietic stem cellsHSC collectionDP infusionChest painMyeloablative conditioningPlatelet engraftmentCell diseaseGroup CAdvisory CommitteeMedical directorsGene therapyMonths of transfusionNon-hematologic gradeGroup C patientsSerious adverse eventsSubstantial clinical benefitLentiviral vectors
2016
Interim Results from a Phase 1/2 Clinical Study of Lentiglobin Gene Therapy for Severe Sickle Cell Disease
Kanter J, Walters M, Hsieh M, Krishnamurti L, Kwiatkowski J, Kamble R, von Kalle C, Kuypers F, Cavazzana M, Leboulch P, Joseney-Antoine M, Asmal M, Thompson A, Tisdale J. Interim Results from a Phase 1/2 Clinical Study of Lentiglobin Gene Therapy for Severe Sickle Cell Disease. Blood 2016, 128: 1176. DOI: 10.1182/blood.v128.22.1176.1176.Peer-Reviewed Original ResearchSevere sickle cell diseaseSevere SCDBone marrow harvestAdverse eventsSickle cell diseaseCell doseBluebird BioReplication-competent lentivirusHematopoietic stem cellsMyeloablative conditioningPeripheral bloodCell diseaseGrade 3 adverse eventsAdvisory CommitteeMedical directorsPhase 1/2 clinical studyTransfusion-dependent β-thalassemiaSerious adverse eventsLong-term complicationsVector copy numberStart of conditioningSymptoms 1 yearIntegration site analysisGene therapyDP infusion
2015
Initial Results from Study Hgb-206: A Phase 1 Study Evaluating Gene Therapy By Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the Lentiglobin BB305 Lentiviral Vector in Subjects with Severe Sickle Cell Disease
Kanter J, Walters M, Hsieh M, Thompson A, Krishnamurti L, Kwiatkowski J, Kamble R, von Kalle C, Kuypers F, Cavazzana M, Leboulch P, Sandler L, Soni S, Tisdale J. Initial Results from Study Hgb-206: A Phase 1 Study Evaluating Gene Therapy By Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the Lentiglobin BB305 Lentiviral Vector in Subjects with Severe Sickle Cell Disease. Blood 2015, 126: 3233. DOI: 10.1182/blood.v126.23.3233.3233.Peer-Reviewed Original ResearchSevere SCDSevere sickle cell diseaseSickle cell diseaseCell diseaseBluebird BioAdverse eventsAutologous CD34Additional subjectsLentiviral vectorsBone marrow harvestVector copy numberIntegration site analysisAdvisory CommitteeGene therapyHematologic engraftmentPRBC transfusionIntravenous busulfanChronic transfusionHb levelsSafety profileAutologous transplantationCell doseStudy visitMonth postProduct infusionResults of a Multicenter Pilot Investigation of Bone Marrow Transplantation in Adults with Sickle Cell Disease (STRIDE)
Krishnamurti L, Sullivan K, Kamani N, Waller E, Abraham A, Campigotto F, Zhang W, Smith S, Hassell K, Decastro L, Wu C, Neuberg D, Walters M. Results of a Multicenter Pilot Investigation of Bone Marrow Transplantation in Adults with Sickle Cell Disease (STRIDE). Blood 2015, 126: 543. DOI: 10.1182/blood.v126.23.543.543.Peer-Reviewed Original ResearchHematopoietic cell transplantationSickle cell diseaseAcute chest syndromeSevere sickle cell diseaseRegurgitant jet velocityAdverse eventsGraft failureUnrelated donorsCell diseaseEligibility criteriaUnrelated donor hematopoietic cell transplantationDonor hematopoietic cell transplantationEvent-free survival probabilityFull donor myeloid chimerismPosterior reversible encephalopathy syndromeDonor myeloid chimerismToxicity conditioning regimenTransplant conditioning regimenUnmodified bone marrowReversible encephalopathy syndromeSerious adverse eventsStandard supportive careTransplant-related toxicityDonor T cellsKaplan-Meier probabilityRandomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use
Telen M, Wun T, McCavit T, De Castro L, Krishnamurti L, Lanzkron S, Hsu L, Smith W, Rhee S, Magnani J, Thackray H. Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use. Blood 2015, 125: 2656-2664. PMID: 25733584, PMCID: PMC4408290, DOI: 10.1182/blood-2014-06-583351.Peer-Reviewed Original ResearchConceptsVaso-occlusive crisisSickle cell diseaseComposite primary end pointPrimary end pointPhase 2 studyEnd pointRandomized phase 2 studySCD vaso-occlusive crisisOpioid analgesic useSecondary end pointsActive treatment groupPhase 3 studyVaso-occlusive eventsAnalgesic usePlacebo groupProspective multicenterStudy drugAdverse eventsOpioid useSymptom reliefMedian timeSCD patientsCell diseaseTreatment groupsAnimal models
2014
PETIT and PETIT 2: Treatment with Eltrombopag in 171 Children with Chronic Immune Thrombocytopenia (ITP)
Bussel J, Grainger J, de Miguel P, Despotovic J, Locatelli F, Chotsampancharoen T, Donyush E, Navarro J, Pongtanakul B, Komvilaisak P, Sosothikul D, Blanchette V, Drelichman G, Krishnamurti L, Sirachainan N, Connor P, David M, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Boayue K, Matthews D, Marcello L, Iyengar M, Chan G, Chagin K, Theodore D, Bakshi K, Bailey C. PETIT and PETIT 2: Treatment with Eltrombopag in 171 Children with Chronic Immune Thrombocytopenia (ITP). Blood 2014, 124: 1450. DOI: 10.1182/blood.v124.21.1450.1450.Peer-Reviewed Original ResearchChronic immune thrombocytopeniaImmune thrombocytopeniaThrombopoietin receptor agonistsAdverse eventsPlatelet count responsePlatelet countStudy treatmentITP medicationsSerious AEsPBO groupRandomized periodX ULNReceptor agonistRandomized phaseTreatment groupsMedian average daily doseOral thrombopoietin receptor agonistUpper respiratory tract infectionMost subjectsAdvisory CommitteeDose of eltrombopagEfficacy of eltrombopagPediatric immune thrombocytopeniaPre-existing cataractCommon adverse eventsA Multi-Center Randomized Controlled Trial of Intravenous Magnesium for Sickle Cell Pain Crisis in Children
Brousseau D, Scott J, Badaki O, Darbari D, Chumpitazi C, Airewele G, Ellison A, Smith-Whitley K, Mahajan P, Sarnaik S, Casper T, Cook L, Dean M, Leonard J, Hulbert M, Powell E, Liem R, Hickey R, Krishnamurti L, Hillery C, Panepinto J. A Multi-Center Randomized Controlled Trial of Intravenous Magnesium for Sickle Cell Pain Crisis in Children. Blood 2014, 124: 88. DOI: 10.1182/blood.v124.21.88.88.Peer-Reviewed Original ResearchSickle cell pain crisisLength of stayAcute chest syndromePediatric Emergency Care Applied Research NetworkQuality of lifePain crisisPediatric emergency medicine physiciansOpioid useIntravenous magnesiumSickle cell diseaseEmergency medicine physiciansMorphine equivalentsPlacebo groupStudy drugAdverse eventsDrug infusionCell diseaseMedicine physiciansHistory of ACSMAGIC studyMulti-Center Randomized Controlled TrialSickle cell vasoocclusive crisisAcute intervention trialDecreased opioid useFirst drug infusion
2011
Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity
Machado R, Barst R, Yovetich N, Hassell K, Kato G, Gordeuk V, Gibbs J, Little J, Schraufnagel D, Krishnamurti L, Girgis R, Morris C, Rosenzweig E, Badesch D, Lanzkron S, Onyekwere O, Castro O, Sachdev V, Waclawiw M, Woolson R, Goldsmith J, Gladwin M. Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood 2011, 118: 855-864. PMID: 21527519, PMCID: PMC3148167, DOI: 10.1182/blood-2010-09-306167.Peer-Reviewed Original ResearchConceptsTricuspid regurgitation velocitySickle cell diseaseLower exercise capacityExercise capacityCell diseaseN-terminal pro-brain natriuretic peptideElevated tricuspid regurgitation velocityPro-brain natriuretic peptideSerious adverse eventsPulmonary arterial hypertensionSildenafil trialArterial hypertensionAdverse eventsWalk distanceDoppler echocardiographySCD patientsHospitalization ratesNatriuretic peptidePatientsSildenafilPredominant causePainHospitalizationTreatment effectsDisease
2009
Safety and Efficacy of Sildenafil Therapy for Doppler-Defined Pulmonary Hypertension in Patients with Sickle Cell Disease: Preliminary Results of the Walk-PHaSST Clinical Trial.
Machado R, Barst R, Yovetich N, Hassell K, Goldsmith J, Woolson R, Gordeuk V, Gibbs S, Little J, Kato G, Schraufnagel D, Krishnamurti L, Girgis R, Morris C, Berman-Rosenzweig E, Badesch D, Waclawiw M, Gladwin M. Safety and Efficacy of Sildenafil Therapy for Doppler-Defined Pulmonary Hypertension in Patients with Sickle Cell Disease: Preliminary Results of the Walk-PHaSST Clinical Trial. Blood 2009, 114: 571. DOI: 10.1182/blood.v114.22.571.571.Peer-Reviewed Original ResearchSerious adverse eventsSickle cell diseaseRight heart catheterizationBrief Pain InventoryPulmonary hypertensionCell diseaseAdverse eventsArterial pressureMean pulmonary arterial pressureSix-minute walk distanceApparent safety issuesDose of sildenafilSecondary endpoint analysisWeeks of sildenafilPulmonary vascular resistancePulmonary arterial pressureTransthoracic Doppler echocardiographySystemic arterial pressurePremature study terminationSingle test doseSignificant differencesSignificant increaseSickle cell anemiaOral sildenafilSildenafil dosing