2023
Reduced Intensity Haploidentical Bone Marrow Transplantation in Adults with Severe Sickle Cell Disease: BMT CTN 1507
Kassim A, Walters M, Eapen M, Ritzau N, Smith M, Solh M, McKinney C, Nieder M, Ross M, Kent M, Abusin G, Mallhi K, Silva J, Shaughnessy P, Kanter J, Haines H, Farah R, Khaled Y, Abraham A, Bollard C, Cooke K, de La Fuente J, Hanna R, Horowitz M, Jordan L, Krishnamurti L, Leifere E, Mahadeo K, Shenoy S, Ritzau N, DeBaun M, Brodsky R. Reduced Intensity Haploidentical Bone Marrow Transplantation in Adults with Severe Sickle Cell Disease: BMT CTN 1507. Blood 2023, 142: lba-4. DOI: 10.1182/blood-2023-192022.Peer-Reviewed Original ResearchPost-transplant cyclophosphamideEvent-free survivalBone marrow transplantSickle cell diseaseSevere sickle cell diseaseTotal body irradiationGraft failureAcute GVHDPost-BMTCell diseaseDay 100Multi-center phase II trialFirst year post-BMTHaploidentical bone marrow transplantVaso-occlusive pain episodesHaploidentical bone marrow transplantationHematopoietic stem cell transplantationChronic transfusion regimenDurable donor engraftmentHemoglobin SS diseaseAcute chest syndromePrimary graft failureSecondary graft failureEnd-organ toxicityPhase II trial
2021
Sustained Improvements in Patient-Reported Quality of Life up to 24 Months Post-Treatment with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy
Walters M, Tisdale J, Mapara M, Krishnamurti L, Kwiatkowski J, Aygun B, Kasow K, Rifkin-Zenenberg S, Jaroscak J, Garbinsky D, Chirila C, Gallagher M, Zhang X, Ho P, Thompson A, Kanter J. Sustained Improvements in Patient-Reported Quality of Life up to 24 Months Post-Treatment with LentiGlobin for Sickle Cell Disease (bb1111) Gene Therapy. Blood 2021, 138: 7. DOI: 10.1182/blood-2021-146905.Peer-Reviewed Original ResearchPain intensity numeric rating scaleNumeric rating scaleVaso-occlusive eventsSickle cell diseasePatient-reported outcomesCurrent equity holderMonth 24Severe vaso-occlusive eventsBaseline scoresQuality of lifeBluebird BioPopulation normsException of anxietyComplete resolutionGroup CSmall sample size limits interpretationMean pain interference scoreSevere sickle cell diseaseUS general population normsAdvisory CommitteePatient-reported QOL outcomesMean pain interferencePain interference scoresPain intensity scoresGroup C patientsPreliminary 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
2019
A Phase II Trial to Compare Allogeneic Transplant Vs. Standard of Care for Severe Sickle Cell Disease: Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 1503
Eapen M, Neuberg D, Mendizabal A, Stevenson K, Antin J, DiFronzo N, Rassi F, Lulla P, Waller E, Garrison J, Smith S, Sullivan K, Walters M, Krishnamurti L. A Phase II Trial to Compare Allogeneic Transplant Vs. Standard of Care for Severe Sickle Cell Disease: Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 1503. Blood 2019, 134: 4592. DOI: 10.1182/blood-2019-126793.Peer-Reviewed Original ResearchSickle cell diseaseHematopoietic cell transplantationSevere sickle cell diseaseUnrelated donorsUnrelated donor hematopoietic cell transplantationDonor hematopoietic cell transplantationCurrent phase II trialMyeloablative conditioning regimenPhase II trialConditioning regimenII trialCurative treatmentCell transplantationTreatment optionsCurrent therapiesCell diseasePilot trialRare diseaseSuitable donorStudy designHLAAge 15Young adultsTrialsGold standardS1633 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 AdultsPatientsBone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study
Krishnamurti L, Neuberg D, Sullivan K, Kamani N, Abraham A, Campigotto F, Zhang W, Dahdoul T, De Castro L, Parikh S, Bakshi N, Haight A, Hassell K, Loving R, Rosenthal J, Smith S, Smith W, Spearman M, Stevenson K, Wu C, Wiedl C, Waller E, Walters M. Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. American Journal Of Hematology 2019, 94: 446-454. PMID: 30637784, PMCID: PMC6542639, DOI: 10.1002/ajh.25401.Peer-Reviewed Original ResearchConceptsSevere sickle cell diseaseBone marrow transplantationEvent-free survivalSickle cell diseaseMarrow transplantationCell diseaseElevated tricuspid regurgitant jet velocityRegular red blood cell transfusionsSevere SCDDonor bone marrow transplantationOne-year overall survivalSecond bone marrow transplantationTricuspid regurgitant jet velocityRed blood cell transfusionProspective multicenter pilot studyDeveloped chronic GVHDHost disease (GVHD) prophylaxisStable donor chimerismAcute chest syndromeSecondary graft failureBlood cell transfusionHealth-related qualityPhysical function domainProspective clinical trialsRegurgitant jet velocity
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 vectors188 Single-Agent Plerixafor Mobilization to Collect Autologous Stem Cells for Use in Gene Therapy for Severe Sickle Cell Disease
Tisdale J, Kanter J, Hsieh M, Krishnamurti L, Kwiatkowski J, Kamble R, von Kalle C, Miller A, Pierciey F, Shi W, Asmal M, Thompson A, Walters M. 188 Single-Agent Plerixafor Mobilization to Collect Autologous Stem Cells for Use in Gene Therapy for Severe Sickle Cell Disease. Transplantation And Cellular Therapy 2018, 24: s174. DOI: 10.1016/j.bbmt.2017.12.108.Peer-Reviewed Original ResearchGene therapyAutologous stem cellsStem cellsSevere sickle cell diseaseSickle cell diseaseCell diseasePlerixafor mobilization
2017
Successful Plerixafor-Mediated Mobilization, Apheresis, and Lentiviral Vector Transduction of Hematopoietic Stem Cells in Patients with Severe Sickle Cell Disease
Tisdale J, Pierciey F, Kamble R, Kanter J, Krishnamurti L, Kwiatkowski J, Thompson A, Shestopalov I, Bonner M, Joseney-Antoine M, Asmal M, Walters M. Successful Plerixafor-Mediated Mobilization, Apheresis, and Lentiviral Vector Transduction of Hematopoietic Stem Cells in Patients with Severe Sickle Cell Disease. Blood 2017, 130: 990. DOI: 10.1182/blood.v130.suppl_1.990.990.Peer-Reviewed Original ResearchSevere sickle cell diseaseSevere SCDPhase 1 studyBM harvestAutologous hematopoietic stem cellsSickle cell diseaseBone marrowBluebird BioHematopoietic stem cellsCell diseaseCultured CD34Cells/G-CSFPeak white blood cellAdvisory CommitteeMedical directorsHSC mobilizationGene therapyGrade 3 AEsPeripheral blood apheresisGroup B patientsAcceptable toxicity profileLife-threatening complicationsTotal blood volumeSteady-state bone marrow
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 infusionA trial of unrelated donor marrow transplantation for children with severe sickle cell disease
Shenoy S, Eapen M, Panepinto J, Logan B, Wu J, Abraham A, Brochstein J, Chaudhury S, Godder K, Haight A, Kasow K, Leung K, Andreansky M, Bhatia M, Dalal J, Haines H, Jaroscak J, Lazarus H, Levine J, Krishnamurti L, Margolis D, Megason G, Yu L, Pulsipher M, Gersten I, DiFronzo N, Horowitz M, Walters M, Kamani N. A trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood 2016, 128: 2561-2567. PMID: 27625358, PMCID: PMC5123194, DOI: 10.1182/blood-2016-05-715870.Peer-Reviewed Original ResearchConceptsEvent-free survivalIncidence rateAcute chest syndrome episodesPosterior reversible encephalopathy syndromeSevere sickle cell diseaseUnrelated donor marrow transplantationVaso-occlusive pain crisesAllogeneic bone marrow transplantEffective GVHD prophylaxisGVHD-related deathsHost disease (GVHD) prophylaxisShort-course methotrexateReversible encephalopathy syndromeUnrelated donor transplantsPhase 2 trialBone marrow transplantTranscranial Doppler velocitiesSickle cell diseaseAcute GVHDChronic GVHDEFS ratesEncephalopathy syndromeGVHD prophylaxisTransplant indicationConditioning regimen
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 probabilityInitial 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 infusionHydroxyurea therapy for children with sickle cell disease: describing how caregivers make this decision
Creary S, Zickmund S, Ross D, Krishnamurti L, Bogen D. Hydroxyurea therapy for children with sickle cell disease: describing how caregivers make this decision. BMC Research Notes 2015, 8: 372. PMID: 26303306, PMCID: PMC4548690, DOI: 10.1186/s13104-015-1344-0.Peer-Reviewed Original Research
2012
Oocyte cryopreservation in a patient with sickle cell disease prior to hematopoietic stem cell transplantation: first report
Dovey S, Krishnamurti L, Sanfilippo J, Gunawardena S, Mclendon P, Campbell M, Alway S, Efymow B, Gracia C. Oocyte cryopreservation in a patient with sickle cell disease prior to hematopoietic stem cell transplantation: first report. Journal Of Assisted Reproduction And Genetics 2012, 29: 265-269. PMID: 22219083, PMCID: PMC3288130, DOI: 10.1007/s10815-011-9698-2.Peer-Reviewed Original ResearchConceptsSickle cell diseaseSevere sickle cell diseaseHematopoietic stem cell transplantationStem cell transplantationVaso-occlusive eventsCell diseaseOvarian stimulationOvarian hyperstimulationFertility preservationCell transplantationOocyte cryopreservationHematopoietic stem cell transplantFertility preservation counselingGnRH antagonist protocolUnique patient populationStem cell transplantYear old femaleSuccessful ovarian stimulationAntagonist protocolCell transplantPatient populationOocyte bankingMulti-disciplinary teamElevated riskOld female
2010
Long-Term Follow-up of Adults with Severe Sickle Cell Disease After Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning
Biernacki M, Okam M, Shenoy S, Krishnamurti L, Horwitz M, Neuberg D, Antin J, Wu C. Long-Term Follow-up of Adults with Severe Sickle Cell Disease After Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning. Blood 2010, 116: 261. DOI: 10.1182/blood.v116.21.261.261.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationSickle cell diseaseSevere sickle cell diseaseLimited chronic GVHDStem cell transplantationLong-term outcomesRIC-HSCTAdult patientsChronic GVHDGraft lossImmunosuppressive medicationsCell transplantationCell diseaseMyeloablative hematopoietic stem cell transplantationMinimal transplant-related toxicityPeripheral blood stem cellsStable donor chimerismSustained donor engraftmentTotal lymphoid irradiationTransplant-related mortalityIntensity conditioning regimensTransplant-related toxicityDisease-free survivalNew adult patientsMajority of patients