2021
Polyclonality Strongly Correlates with Biological Outcomes and Is Significantly Increased Following Improvements to the Phase 1/2 HGB-206 Protocol and Manufacturing of LentiGlobin for Sickle Cell Disease (SCD; bb1111) Gene Therapy (GT)
Tisdale J, Thompson A, Mapara M, Kwiatkowski J, Krishnamurti L, Aygun B, Kasow K, Rifkin-Zenenberg S, Schmidt M, Pierciey F, Whitney D, Rogers C, Nnamani M, Foos M, Miller A, Zhang X, Lynch J, Walters M, Kanter J, Bonner M. Polyclonality Strongly Correlates with Biological Outcomes and Is Significantly Increased Following Improvements to the Phase 1/2 HGB-206 Protocol and Manufacturing of LentiGlobin for Sickle Cell Disease (SCD; bb1111) Gene Therapy (GT). Blood 2021, 138: 561. DOI: 10.1182/blood-2021-147760.Peer-Reviewed Original ResearchAcute myeloid leukemiaVaso-occlusive eventsCurrent equity holderSevere vaso-occlusive eventsGroup AGroup CMonth 6Clinical outcomesBluebird BioClinical benefitBusulfan conditioningCell doseRisk of AMLAutologous stem cell transplantTricuspid regurgitant jet velocityAdvisory CommitteeDriver mutationsLentiviral vectorsAML driver mutationsOpioid withdrawal syndromeSerious adverse eventsRegurgitant jet velocityFavorable clinical outcomeConsultancy feesStem cell transplant
2020
Lentiglobin 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
Preliminary Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of BCL11A in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia
Smith A, Schiller G, Vercellotti G, Kwiatkowski J, Krishnamurti L, Esrick E, Williams D, Miller W, Woolfson A, Walters M. Preliminary Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of BCL11A in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia. Blood 2019, 134: 3544. DOI: 10.1182/blood-2019-125743.Peer-Reviewed Original ResearchTransfusion-dependent beta thalassemiaPeripheral blood mononuclear cellsSerious adverse eventsHematopoietic stem cell transplantationHuman hematopoietic stem cellsHematopoietic reconstitutionBluebird BioPRBC transfusionPatient 1HbF levelsG-CSFJazz PharmaceuticalsPacked red blood cell transfusionPhase I/II studyAllogeneic hematopoietic stem cell transplantationRed blood cell transfusionHematopoietic stem cellsPhase 1/2 clinical studyBeta thalassemiaInvestigational cell therapySpeakers bureauBlood cell transfusionStem cell transplantationBlood mononuclear cellsCells/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
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 SCD
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
Results 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 probability
2013
An Analysis Of The Pediatric Sub-Group From The Phase 2 Study Of GMI 1070 – A Novel Agent For The Vaso-Occlusive Crisis Of Sickle Cell Anemia
McCavit T, Krishnamurti L, Hsu L, Quinn C, Odame I, Alvarez O, Driscoll C, Smith-Whitley K, Rhee S, Wun T, Telen M, Thackray H. An Analysis Of The Pediatric Sub-Group From The Phase 2 Study Of GMI 1070 – A Novel Agent For The Vaso-Occlusive Crisis Of Sickle Cell Anemia. Blood 2013, 122: 2206. DOI: 10.1182/blood.v122.21.2206.2206.Peer-Reviewed Original ResearchVaso-occlusive crisisSerious adverse eventsSickle cell anemiaAcute chest syndromeStudy drugPediatric subjectsAdult subjectsMaintenance dosesOpioid useSecondary outcomesMedian timePlacebo-controlled phase 2 trialCell anemiaRed blood cell transfusionPhase 3 clinical trialsStrong efficacy signalBlood cell transfusionPhase 2 studyPhase 2 trialKaplan-Meier methodVisual analog scaleInitial medical evaluationPan-selectin inhibitorAdvisory CommitteeMinimal safety concerns
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 effectsDiseaseNitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis: A Randomized Controlled Trial
Gladwin M, Kato G, Weiner D, Onyekwere O, Dampier C, Hsu L, Hagar R, Howard T, Nuss R, Okam M, Tremonti C, Berman B, Villella A, Krishnamurti L, Lanzkron S, Castro O, Gordeuk V, Coles W, Peters-Lawrence M, Nichols J, Hall M, Hildesheim M, Blackwelder W, Baldassarre J, Casella J, Investigators F. Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis: A Randomized Controlled Trial. JAMA 2011, 305: 893-902. PMID: 21364138, PMCID: PMC3403835, DOI: 10.1001/jama.2011.235.Peer-Reviewed Original ResearchConceptsVaso-occlusive pain crisesSickle cell diseaseVisual analog pain scale scoreAcute chest syndromePrimary end pointPain scale scoresNitric oxideChest syndromePain crisisPainful crisesScale scoreSickle cell pain crisisSmall placebo-controlled trialsPlacebo-controlled clinical trialEnd pointNitric oxide gasCumulative opioid usageParenteral opioid useWhole blood nitritePlacebo-controlled trialSerious adverse eventsLength of hospitalizationSecondary outcome measuresEvidence of efficacyOpioid usage
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