2024
Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease
Lessard S, Rimmelé P, Ling H, Moran K, Vieira B, Lin Y, Rajani G, Hong V, Reik A, Boismenu R, Hsu B, Chen M, Cockroft B, Uchida N, Tisdale J, Alavi A, Krishnamurti L, Abedi M, Galeon I, Reiner D, Wang L, Ramezi A, Rendo P, Walters M, Levasseur D, Peters R, Harris T, Hicks A. Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease. Scientific Reports 2024, 14: 24298. PMID: 39414860, PMCID: PMC11484757, DOI: 10.1038/s41598-024-74716-7.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsSickle cell diseaseTreatment of sickle cell diseaseFetal hemoglobinCell therapyReactivation of fetal hemoglobinCell diseaseMonths of follow-upStem cellsReactivate fetal hemoglobinResults of preclinical studiesPotential treatmentEngraftment in vivoAutologous cell therapyNovel cell therapiesVaso-occlusive crisisIncreased total hemoglobinErythroid progenyHealthy donorsPreclinical studiesClinical developmentFollow-upErythroid enhancerBCL11A erythroid enhancerGATAA motifs
2023
Distributional Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease in the United States.
Goshua G, Calhoun C, Ito S, James L, Luviano A, Krishnamurti L, Pandya A. Distributional Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease in the United States. Annals Of Internal Medicine 2023, 176: 779-787. PMID: 37247420, PMCID: PMC10370480, DOI: 10.7326/m22-3272.Peer-Reviewed Original Research
2022
Multimodal phenotyping and correlates of pain following hematopoietic cell transplant in children with sickle cell disease
Bakshi N, Astles R, Chou E, Hurreh A, Sil S, Sinha C, Sanders K, Peddineni M, Gillespie S, Keesari R, Krishnamurti L. Multimodal phenotyping and correlates of pain following hematopoietic cell transplant in children with sickle cell disease. Pediatric Blood & Cancer 2022, 70: e30046-e30046. PMID: 36322607, PMCID: PMC9820671, DOI: 10.1002/pbc.30046.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantPatient-reported outcomesSickle cell diseaseYear post-HCTPost-HCTExperimental pain sensitivitySickle cell anemiaCell transplantPain thresholdPain sensitivityCell diseaseCorrelates of painPressure pain thresholdHealth-related qualityCold pain thresholdAssessment of painPsychological factorsUnderstanding of painEffect sizePain assessmentObservational studySevere genotypePainCell anemiaOptional substudies
2020
Mortality in sickle cell disease: A population‐based study in an aboriginal community in the Gudalur Valley, Nilgiris, Tamil Nadu, India
Sheshadri V, Shabeer P, Santhirapala V, Jayaram A, Krishnamurti L, Menon N. Mortality in sickle cell disease: A population‐based study in an aboriginal community in the Gudalur Valley, Nilgiris, Tamil Nadu, India. Pediatric Blood & Cancer 2020, 68: e28875. PMID: 33381914, DOI: 10.1002/pbc.28875.Peer-Reviewed Original ResearchConceptsSickle cell diseaseCause of deathCell diseaseMortality rateSeverity of SCDAge groupsAboriginal populationAcute chest syndromePopulation-based studyPercent of deathsCrude mortality rateCommunity-based comprehensive careCause of mortalityCases of deathPaucity of dataCommon monogenic disorderChest syndromeMedian ageHospital recordsSCD patientsAutopsy questionnaireAboriginal communitiesComprehensive careLongitudinal cohortRemote Aboriginal communitiesPrimary caregiver decision‐making in hematopoietic cell transplantation and gene therapy for sickle cell disease
Sinha C, Bakshi N, Ross D, Loewenstein G, Krishnamurti L. Primary caregiver decision‐making in hematopoietic cell transplantation and gene therapy for sickle cell disease. Pediatric Blood & Cancer 2020, 68: e28749-e28749. PMID: 33034129, PMCID: PMC8246626, DOI: 10.1002/pbc.28749.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantationSickle cell diseasePrimary caregiversSCD complicationsCell transplantationCell diseaseDiminished qualityAutologous hematopoietic progenitor cellsPrimary caregiver reportMajor medical decisionsGene therapyCurative optionSevere complicationsHematopoietic progenitor cellsClinical trialsAcceptable treatmentRecent complicationsComplicationsCaregiver reportsCaregiversProgenitor cellsNormal lifeTransplantationTherapyMedical decisionsSafety and feasibility of hematopoietic progenitor stem cell collection by mobilization with plerixafor followed by apheresis vs bone marrow harvest in patients with sickle cell disease in the multi‐center HGB‐206 trial
Tisdale J, Pierciey F, Bonner M, Thompson A, Krishnamurti L, Mapara M, Kwiatkowski J, Shestopalov I, Ribeil J, Huang W, Asmal M, Kanter J, Walters M. Safety and feasibility of hematopoietic progenitor stem cell collection by mobilization with plerixafor followed by apheresis vs bone marrow harvest in patients with sickle cell disease in the multi‐center HGB‐206 trial. American Journal Of Hematology 2020, 95: e239-e242. PMID: 32401372, DOI: 10.1002/ajh.25867.Peer-Reviewed Original ResearchAssessment of Patient and Caregiver Attitudes and Approaches to Decision-Making Regarding Bone Marrow Transplant for Sickle Cell Disease
Bakshi N, Katoch D, Sinha C, Ross D, Quarmyne M, Loewenstein G, Krishnamurti L. Assessment of Patient and Caregiver Attitudes and Approaches to Decision-Making Regarding Bone Marrow Transplant for Sickle Cell Disease. JAMA Network Open 2020, 3: e206742. PMID: 32469414, PMCID: PMC7260617, DOI: 10.1001/jamanetworkopen.2020.6742.Peer-Reviewed Original ResearchConceptsBone marrow transplantCaregivers of patientsSickle cell diseasePatient decision aidMarrow transplantMedian ageCurative treatmentCell diseaseGroup 2Group 1Caregiver attitudesNovel disease-modifying therapiesDisease-modifying therapiesSickle cell clinicAssessment of patientsFuture prospective studiesRandomized clinical trialsParent trialProspective studyTreatment optionsClinical trialsNeeds assessment phaseMAIN OUTCOMECell clinicPatientsShould young children with sickle cell disease and an available human leukocyte antigen identical sibling donor be offered hematopoietic cell transplantation?
Krishnamurti L. Should young children with sickle cell disease and an available human leukocyte antigen identical sibling donor be offered hematopoietic cell transplantation? Hematology/Oncology And Stem Cell Therapy 2020, 13: 53-57. PMID: 32202246, DOI: 10.1016/j.hemonc.2019.12.008.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantationSickle cell diseaseQuality of lifeOverall survivalCell transplantationCell diseaseYoung childrenHLA-identical siblingsHuman leukocyte antigenSevere clinical presentationAvailable human leukocyte antigenFree survivalOrgan dysfunctionClinical presentationLeukocyte antigenIdentical siblingsPremature mortalityAvailable HLAYounger ageTransplantationHLAAgeDiseaseChildrenSurvival
2019
How I treat sickle cell disease with hematopoietic cell transplantation
Stenger E, Shenoy S, Krishnamurti L. How I treat sickle cell disease with hematopoietic cell transplantation. Blood 2019, 134: 2249-2260. PMID: 31697818, PMCID: PMC6923666, DOI: 10.1182/blood.2019000821.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantationSickle cell diseaseCell transplantationCell diseaseOrgan dysfunctionSCD patientsSignificant morbidityEarly mortalityClinical trialsAvailable cureSCD recipientsAlternative donorsIndividual patientsClinical practicePatientsTransplantationClinical vignettesDiseaseOutcomesMorbidityDysfunctionMortalityTrialsRecipientsComparative Effectiveness of a Web-Based Patient Decision Aid for Therapeutic Options for Sickle Cell Disease: Randomized Controlled Trial
Krishnamurti L, Ross D, Sinha C, Leong T, Bakshi N, Mittal N, Veludhandi D, Pham A, Taneja A, Gupta K, Nwanze J, Matthews A, Joshi S, Olivieri V, Arjunan S, Okonkwo I, Lukombo I, Lane P, Bakshi N, Loewenstein G. Comparative Effectiveness of a Web-Based Patient Decision Aid for Therapeutic Options for Sickle Cell Disease: Randomized Controlled Trial. Journal Of Medical Internet Research 2019, 21: e14462. PMID: 31799940, PMCID: PMC6934048, DOI: 10.2196/14462.Peer-Reviewed Original ResearchConceptsRandomized clinical trialsPatient decision aidSickle cell diseaseWeb-based patient decision aidClinical trialsHealth care providersCell diseaseDecisional conflictPatient knowledgeCare providersDecision aid armStandard care armOttawa Decision Support FrameworkChronic blood transfusionsDisease-modifying therapiesBone marrow transplantationDecision aidCare armDecision aid prototypeClinical characteristicsBlood transfusionControlled TrialsPediatric patientsMarrow transplantationTherapeutic optionsManagement of Chronic Pain in Adults Living With Sickle Cell Disease in the Era of the Opioid Epidemic
Sinha C, Bakshi N, Ross D, Krishnamurti L. Management of Chronic Pain in Adults Living With Sickle Cell Disease in the Era of the Opioid Epidemic. JAMA Network Open 2019, 2: e194410. PMID: 31125105, PMCID: PMC6632133, DOI: 10.1001/jamanetworkopen.2019.4410.Peer-Reviewed Original ResearchConceptsSickle cell diseaseOpioid epidemicOpioid usePain managementChronic painAlternative therapiesCell diseaseAfrican American race/ethnicityDisease controlVaso-occlusive painPain medication useChronic pain managementSickle cell clinicCurrent opioid epidemicRace/ethnicityOpioid dosingOpioid dosageOpioid prescriptionsAdult patientsMedian ageMedication usePersistent painComprehensive careMAIN OUTCOMEPainBone 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
Platelet transfusion practices in immune thrombocytopenia related hospitalizations
Goel R, Chopra S, Tobian A, Ness P, Frank S, Cushing M, Vasovic L, Kaicker S, Takemoto C, Josephson C, Nellis M, Bussel J, Krishnamurti L. Platelet transfusion practices in immune thrombocytopenia related hospitalizations. Transfusion 2018, 59: 169-176. PMID: 30520045, DOI: 10.1111/trf.15069.Peer-Reviewed Original ResearchConceptsPlatelet transfusion practicesImmune thrombocytopeniaPlatelet transfusionsNational Inpatient SampleAdmission diagnosisTransfusion practiceCurrent guidelinesHigher mean total hospital chargesMean total hospital chargesSmall bed size hospitalsMultivariable logistic regression analysisPayer inpatient databasePrimary admission diagnosisSurgery/procedureTotal hospital chargesMajor operative proceduresLogistic regression analysisNon-teaching hospitalsInvasive surgical proceduresHospital mortalityMultivariable adjustmentITP patientsClinical outcomesRelated hospitalizationsHospital chargesA Qualitative Study of Chronic Pain and Self-Management in Adults with Sickle Cell Disease
Matthie N, Ross D, Sinha C, Khemani K, Bakshi N, Krishnamurti L. A Qualitative Study of Chronic Pain and Self-Management in Adults with Sickle Cell Disease. Journal Of The National Medical Association 2018, 111: 158-168. PMID: 30266214, PMCID: PMC6433553, DOI: 10.1016/j.jnma.2018.08.001.Peer-Reviewed Original ResearchConceptsSickle cell diseaseChronic pain managementChronic painChronic pain experiencePain managementCell diseasePain experienceChronic SCD painGreater QoL impairmentVaso-occlusive painYears of ageSelf-management strategiesSickle cell anemiaSubgroup of adultsSCD painAcute painPersistent painSubstantial morbidityHealthcare utilizationImpaired qualityQoL impairmentPainSCD managementCell anemiaQualitative studyFrom trust to skepticism: An in-depth analysis across age groups of adults with sickle cell disease on their perspectives regarding hydroxyurea
Sinha C, Bakshi N, Ross D, Krishnamurti L. From trust to skepticism: An in-depth analysis across age groups of adults with sickle cell disease on their perspectives regarding hydroxyurea. PLOS ONE 2018, 13: e0199375. PMID: 29949647, PMCID: PMC6021071, DOI: 10.1371/journal.pone.0199375.Peer-Reviewed Original ResearchConceptsSickle cell diseaseGroup 1 participantsGroup 2 participantsCell diseaseSide effectsAdult SCD patientsPatient-related factorsPotential side effectsAdult patientsSCD patientsHU usePatients' attitudesAge 31Age groupsAge 18PatientsYoung adultsEfficacySignificant differencesAdultsEffective alternativeDiseaseRiskParticipantsQualitative interviews
2017
Proponent or collaborative: Physician perspectives and approaches to disease modifying therapies in sickle cell disease
Bakshi N, Sinha C, Ross D, Khemani K, Loewenstein G, Krishnamurti L. Proponent or collaborative: Physician perspectives and approaches to disease modifying therapies in sickle cell disease. PLOS ONE 2017, 12: e0178413. PMID: 28727801, PMCID: PMC5518995, DOI: 10.1371/journal.pone.0178413.Peer-Reviewed Original ResearchConceptsSickle cell diseaseChronic blood transfusionsBone marrow transplantationDisease-modifying therapiesTreatment-related decisionsTreatment optionsCell diseasePhysician perspectivesAvailable disease-modifying therapiesLong-term adverse effectsPhysician-related factorsAvailable treatment optionsDisease-related factorsPossible treatment optionsPatients/familiesInherited blood disorderBlood transfusionMarrow transplantationPhysician interviewsPatient burdenPhysicians' perceptionsPatient's perspectivePhysicians' approachPatient engagementTreatment planDetermining the longitudinal validity and meaningful differences in HRQL of the PedsQL™ Sickle Cell Disease Module
Panepinto J, Paul Scott J, Badaki-Makun O, Darbari D, Chumpitazi C, Airewele G, Ellison A, Smith-Whitley K, Mahajan P, Sarnaik S, Charles Casper T, Cook L, Leonard J, Hulbert M, Powell E, Liem R, Hickey R, Krishnamurti L, Hillery C, Brousseau D, for the Pediatric Emergency Care Applied Research Network (PECARN). Determining the longitudinal validity and meaningful differences in HRQL of the PedsQL™ Sickle Cell Disease Module. Health And Quality Of Life Outcomes 2017, 15: 124. PMID: 28606098, PMCID: PMC5468970, DOI: 10.1186/s12955-017-0700-2.Peer-Reviewed Original ResearchConceptsSickle Cell Disease ModuleDisease-specific HRQL instrumentsHealth-related qualityPatient-centered outcomesProspective trial designSickle cell diseaseSpecific HRQL instrumentsHRQL assessmentHRQL instrumentsLongitudinal validityAncillary studiesCell diseaseTrial designHealth statusDisease modulesTime pointsPedsQLMeaningful changeChildrenHRQLPatientsHospitalDiseasePsychological Characteristics and Pain Frequency Are Associated With Experimental Pain Sensitivity in Pediatric Patients With Sickle Cell Disease
Bakshi N, Lukombo I, Shnol H, Belfer I, Krishnamurti L. Psychological Characteristics and Pain Frequency Are Associated With Experimental Pain Sensitivity in Pediatric Patients With Sickle Cell Disease. Journal Of Pain 2017, 18: 1216-1228. PMID: 28602692, DOI: 10.1016/j.jpain.2017.05.005.Peer-Reviewed Original ResearchConceptsSickle cell diseaseExperimental pain stimuliExperimental pain sensitivityPain sensitivityPain stimuliChronic painExperimental painCell diseasePsychological characteristicsQuantitative sensory testing methodsPsychological factorsChronic SCD painMechanical temporal summationVaso-occlusive painQuantitative sensory testingSubset of patientsPain-related outcomesStudy of patientsCross-sectional assessmentChildren ages 8SCD painPain burdenPain frequencyPediatric patientsPain processingNovel Metrics in the Longitudinal Evaluation of Pain Data in Sickle Cell Disease
Bakshi N, Smith M, Ross D, Krishnamurti L. Novel Metrics in the Longitudinal Evaluation of Pain Data in Sickle Cell Disease. The Clinical Journal Of Pain 2017, 33: 517-527. PMID: 27584817, DOI: 10.1097/ajp.0000000000000431.Peer-Reviewed Original ResearchConceptsMaximum daily painSickle cell diseasePain intensity dataChronic painCell diseasePain dataInterindividual variationMaximum daily pain scoresPatient-reported end pointsDaily pain scoresPain-free daysInterventional clinical trialsBurden of painPeriod of hospitalizationElectronic pain diaryDiary daysHealth care providersPain burdenPain scoresPain diaryPain intensityDaily painSCD patientsPain trendsClinical trialsBone Marrow–Derived Mesenchymal Stromal Cells from Patients with Sickle Cell Disease Display Intact Functionality
Stenger E, Chinnadurai R, Yuan S, Garcia M, Arafat D, Gibson G, Krishnamurti L, Galipeau J. Bone Marrow–Derived Mesenchymal Stromal Cells from Patients with Sickle Cell Disease Display Intact Functionality. Transplantation And Cellular Therapy 2017, 23: 736-745. PMID: 28132869, PMCID: PMC5390328, DOI: 10.1016/j.bbmt.2017.01.081.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnemia, Sickle CellCell CommunicationCell Culture TechniquesCell ProliferationChildChild, PreschoolFemaleHealthy VolunteersHematopoietic Stem Cell TransplantationHumansImmunophenotypingIndoleamine-Pyrrole 2,3,-DioxygenaseMaleMesenchymal Stem Cell TransplantationMesenchymal Stem CellsTransplantation, AutologousYoung AdultConceptsSickle cell diseaseHematopoietic cell transplantationMesenchymal stromal cellsAutologous mesenchymal stromal cellsBone marrowTime of HCTAutologous T cell proliferationStromal cellsThird-party mesenchymal stromal cellsBM-derived mesenchymal stromal cellsMajor histocompatibility complex compatibilityExperimental murine modelT cell proliferationSurface marker phenotypeDose-dependent mannerIFN-γ stimulationAmeliorate graftHost diseaseSCD patientsCell transplantationImmunomodulatory pathwaysSCD subjectsCell diseaseHealthy volunteersMurine model