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 motifsSickle cell disease in India: current status and progress
Jain D, Gupta M, Madkaikar M, Jena R, Khargekar N, Saraf S, Krishnamurti L, Gupta K. Sickle cell disease in India: current status and progress. The Lancet Haematology 2024, 11: e322-e323. PMID: 38701819, DOI: 10.1016/s2352-3026(24)00109-1.Peer-Reviewed Original Research
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 ResearchFemale Reproductive Health Outcomes after Hematopoietic Cell Transplantation for Sickle Cell Disease: Is Reduced Intensity Better Than Myeloablative Conditioning?
Meacham L, George S, Veludhandi A, Pruett M, Haight A, Arnold S, Elchuri S, Stenger E, Krishnamurti L. Female Reproductive Health Outcomes after Hematopoietic Cell Transplantation for Sickle Cell Disease: Is Reduced Intensity Better Than Myeloablative Conditioning? Transplantation And Cellular Therapy 2023, 29: 531.e1-531.e4. PMID: 37169288, DOI: 10.1016/j.jtct.2023.05.004.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Sickle CellChildFemaleHematopoietic Stem Cell TransplantationHumansInfertilityMelphalanPrimary Ovarian InsufficiencyReproductive HealthConceptsHematopoietic cell transplantationReduced-intensity conditioningPremature ovarian insufficiencySickle cell diseaseNormal AMH levelsMyeloablative conditioningAnti-Müllerian hormoneOvarian outcomeAMH levelsCell transplantationCell diseaseRIC HCTFollicle-stimulating hormone levelsPediatric oncology patientsRisk of infertilityMIU/mLStudy 2 patientsReproductive health outcomesMelphalan regimenConditioning regimenGonadal damageOvarian damageConditioning regimensOvarian reserveRIC regimensParental perspective on the risk of infertility and fertility preservation options for children and adolescents with sickle cell disease considering hematopoietic stem cell transplantation
Sinha C, Meacham L, Bakshi N, Ross D, Krishnamurti L. Parental perspective on the risk of infertility and fertility preservation options for children and adolescents with sickle cell disease considering hematopoietic stem cell transplantation. Pediatric Blood & Cancer 2023, 70: e30276. PMID: 37051746, PMCID: PMC10544372, DOI: 10.1002/pbc.30276.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationRisk of infertilitySickle cell diseaseStem cell transplantationFertility preservationCell transplantationCell diseaseMajor long-term complicationPrimary caregiversIdentical related donorsDisease-free survivalFertility preservation optionsFertility preservation proceduresLong-term complicationsHuman leukocyte antigenConditioning regimenHost diseaseRelated donorsLeukocyte antigenPreservation optionsHCT physiciansSurvival rateAvailable HLAEleven participantsInfertilitySecondary Neoplasms After Hematopoietic Cell Transplant for Sickle Cell Disease
Eapen M, Brazauskas R, Williams D, Walters M, St Martin A, Jacobs B, Antin J, Bona K, Chaudhury S, Coleman-Cowger V, DiFronzo N, Esrick E, Field J, Fitzhugh C, Kanter J, Kapoor N, Kohn D, Krishnamurti L, London W, Pulsipher M, Talib S, Thompson A, Waller E, Wun T, Horowitz M. Secondary Neoplasms After Hematopoietic Cell Transplant for Sickle Cell Disease. Journal Of Clinical Oncology 2023, 41: 2227-2237. PMID: 36623245, PMCID: PMC10448940, DOI: 10.1200/jco.22.01203.Peer-Reviewed Original ResearchConceptsLow-intensity regimensSickle cell diseaseSecondary neoplasmsRisk factorsCell diseaseLeukemia/myelodysplastic syndromeMixed donor chimerismReduced-intensity regimensFull donor chimerismHematopoietic cell transplantTotal body irradiationLow-dose radiationGray regression modelsMyeloid mutationsPrior inflammationCell transplantMyelodysplastic syndromeTolerance inductionIntense regimensPlausible etiologyHigh riskRegimensSolid tumorsNeoplasmsMyeloid malignancies
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 ResearchMeSH KeywordsAdolescentAnemia, Sickle CellChildFemaleHematopoietic Stem Cell TransplantationHumansMalePainQuality of LifeTransplantation ConditioningConceptsHematopoietic 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 substudiesLong-Term Organ Function After HCT for SCD: A Report From the Sickle Cell Transplant Advocacy and Research Alliance
Stenger E, Xiang Y, Wetzel M, Gillespie S, Chellapandian D, Shah R, Arnold S, Bhatia M, Chaudhury S, Eckrich M, Kanter J, Kasow K, Krajewski J, Nickel R, Ngwube A, Olson T, Rangarajan H, Wobma H, Guilcher G, Horan J, Krishnamurti L, Shenoy S, Abraham A. Long-Term Organ Function After HCT for SCD: A Report From the Sickle Cell Transplant Advocacy and Research Alliance. Transplantation And Cellular Therapy 2022, 29: 47.e1-47.e10. PMID: 36273784, DOI: 10.1016/j.jtct.2022.10.012.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Sickle CellGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansRetrospective StudiesTransplantation, HomologousConceptsHematopoietic cell transplantationSickle cell diseaseOrgan functionMultivariable analysisBrain magnetic resonance imagingCentral nervous system indicationsPost-HCT patientsRelated bone marrowSevere acute GVHDPredictors of dysfunctionLong-term survivalMagnetic resonance imagingSevere clinical phenotypeAcute GVHDChronic graftIntense conditioningHost diseaseMyeloablative conditioningNeurologic eventsOvert strokeRetrospective cohortMedian ageOrgan dysfunctionCardiac dysfunctionCell transplantationEnrollment Lessons from a Biological Assignment Study of Marrow Transplantation versus Standard Care for Adolescents and Young Adults with Sickle Cell Disease: Considerations for Future Gene and Cellular Therapy Trials
Krishnamurti L, Neuberg D, Sullivan K, Smith S, Eapen M, Walters M. Enrollment Lessons from a Biological Assignment Study of Marrow Transplantation versus Standard Care for Adolescents and Young Adults with Sickle Cell Disease: Considerations for Future Gene and Cellular Therapy Trials. Transplantation And Cellular Therapy 2022, 29: 217-221. PMID: 36270432, PMCID: PMC10539686, DOI: 10.1016/j.jtct.2022.10.008.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAgedAnemia, Sickle CellBone MarrowBone Marrow TransplantationCOVID-19HumansMedicareUnited StatesUnrelated DonorsYoung AdultConceptsBone marrow transplantationSickle cell diseaseMarrow transplantationNonmalignant diseasesCell diseaseAdult sickle cell diseaseMyeloablative bone marrow transplantationSingle-arm feasibility studyYoung adultsCellular therapy trialsMulticenter National InstituteRegimen-related toxicitySingle-arm studyFrequency of HLACoronavirus disease 2019 (COVID-19) pandemicAcademic medical centerDisease 2019 pandemicShort-term endpointsBMT centersBMT regimenCare armPain episodesPrimary endpointStandard careCurative therapy
2021
Hematopoietic cell transplantation for sickle cell disease: updates and future directions
Krishnamurti L. Hematopoietic cell transplantation for sickle cell disease: updates and future directions. Hematology 2021, 2021: 181-189. PMID: 34889368, PMCID: PMC8791142, DOI: 10.1182/hematology.2021000251.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantationSickle cell diseaseCell transplantationAlternative donorsCell diseaseOutcomes of HCTHLA-identical related donorsSymptomatic sickle cell diseaseNew disease-modifying drugsHost disease (GVHD) prophylaxisHLA-identical siblingsAvailable therapeutic optionsDisease-modifying drugsLong-term outcomesCord blood expansionConditioning regimensDisease prophylaxisRelated donorsOrgan damageHematopoietic progenitor cellsTherapeutic optionsExcellent outcomesCareful counselingAutologous transplantationClinical registryIntraindividual pain variability and phenotypes of pain in sickle cell disease: a secondary analysis from the Pain in Sickle Cell Epidemiology Study
Bakshi N, Gillespie S, McClish D, McCracken C, Smith W, Krishnamurti L. Intraindividual pain variability and phenotypes of pain in sickle cell disease: a secondary analysis from the Pain in Sickle Cell Epidemiology Study. Pain 2021, 163: 1102-1113. PMID: 34538841, PMCID: PMC9100443, DOI: 10.1097/j.pain.0000000000002479.Peer-Reviewed Original ResearchMeSH KeywordsAnalgesics, OpioidAnemia, Sickle CellHumansOpioid-Related DisordersPainPhenotypeQuality of LifeConceptsSickle cell diseaseSickle Cell Epidemiology StudyOpioid useMean painPain variabilityPhysical functionPain intensityPain phenotypesPatient outcomesCell diseaseEpidemiology studiesHigher mean painLower mean painLow physical functionHealth-related qualityHealth care utilizationHigher physical functionProportion of daysSomatic symptom burdenSymptom burdenCare utilizationPainSecondary analysisSpearman rank correlationHigh temporal instabilityHematopoietic Cell Transplantation Outcomes among Medicaid and Privately Insured Patients with Sickle Cell Disease
Mupfudze T, Meyer C, Preussler J, Mau L, Bolon Y, Steinert P, Arnold S, Saber W, Krishnamurti L. Hematopoietic Cell Transplantation Outcomes among Medicaid and Privately Insured Patients with Sickle Cell Disease. Transplantation And Cellular Therapy 2021, 27: 685.e1-685.e8. PMID: 33895405, PMCID: PMC8680220, DOI: 10.1016/j.jtct.2021.04.009.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Sickle CellHematopoietic Stem Cell TransplantationHumansInsurance, HealthMedicaidRetrospective StudiesUnited StatesConceptsEvent-free survivalSickle cell diseaseHematopoietic cell transplantation outcomesSignificant between-group differencesGraft failureOverall survivalChronic GVHDCell transplantation outcomesBetween-group differencesAcute GVHDCumulative incidenceAlloHCT outcomesTransplantation outcomesInsurance statusCell diseaseAllogeneic hematopoietic cell transplantation outcomesLower event-free survivalPrivate insuranceRecipients of MedicaidProportion of patientsRetrospective multicenter studyKaplan-Meier methodPrivate insurance groupMarrow Transplant ResearchHealth insurance statusA pilot study of the acceptability, feasibility and safety of yoga for chronic pain in sickle cell disease
Bakshi N, Cooley A, Ross D, Hawkins L, Sullivan M, Astles R, Sinha C, Katoch D, Peddineni M, Gee B, Lane P, Krishnamurti L. A pilot study of the acceptability, feasibility and safety of yoga for chronic pain in sickle cell disease. Complementary Therapies In Medicine 2021, 59: 102722. PMID: 33892094, PMCID: PMC8284565, DOI: 10.1016/j.ctim.2021.102722.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnemia, Sickle CellChronic PainFeasibility StudiesFemaleHumansPilot ProjectsYogaConceptsProportion of participantsSafety of yogaChronic painSickle cell diseaseYoga sessionsYoga programED visitsMedian ageCell diseasePart ARetention of participantsFeasibility endpointsPain characteristicsPart BPain diaryAdolescent patientsYoga interventionClinical trialsPatient participantsSafety outcomesPainPilot studyMost participantsStudy assessmentYogaGaps in Medicaid Coverage and Financial Toxicity: A Health Disparity in Hematopoietic Cell Transplantation for Sickle Cell Disease
Krishnamurti L. Gaps in Medicaid Coverage and Financial Toxicity: A Health Disparity in Hematopoietic Cell Transplantation for Sickle Cell Disease. Transplantation And Cellular Therapy 2021, 27: 284-285. PMID: 33836866, DOI: 10.1016/j.jtct.2021.03.016.Peer-Reviewed Original Research
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 communitiesEducational needs of patients and caregivers living with sickle cell disease results in development of web‐based patient decision aid
Ross D, Sinha C, Bakshi N, Krishnamurti L. Educational needs of patients and caregivers living with sickle cell disease results in development of web‐based patient decision aid. Journal Of Advanced Nursing 2020, 77: 1432-1441. PMID: 33277763, DOI: 10.1111/jan.14704.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnemia, Sickle CellCaregiversDecision Support TechniquesHumansInternetQuality of LifeConceptsSickle cell diseasePatients/caregiversWeb-based patient decision aidQuality of lifeTreatment optionsCell diseasePatient decision aidWeb-based decision aidPotential treatment optionHealthcare provider educationInitial needs assessmentDecision aidAdult patientsAvailable therapiesProvider educationSemi-structured qualitative interviewsPatientsHealthcare providersWay patientsDecisional needsInternet-based searchDiseaseCaregiversFurther recruitmentNeeds assessmentPrimary 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 clinicPatientsPatient and family experience with chronic transfusion therapy for sickle cell disease: A qualitative study
Hawkins L, Sinha C, Ross D, Yee M, Quarmyne M, Krishnamurti L, Bakshi N. Patient and family experience with chronic transfusion therapy for sickle cell disease: A qualitative study. BMC Pediatrics 2020, 20: 172. PMID: 32305060, PMCID: PMC7165370, DOI: 10.1186/s12887-020-02078-w.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnemia, Sickle CellBlood TransfusionChelation TherapyChildHumansParentsQualitative ResearchConceptsChronic transfusion therapySickle cell diseaseTransfusion therapyCell diseaseHealthcare providersPrevention of complicationsFamily experiencesStroke preventionVenous accessPatient knowledgeChildren 12Future studiesPatient participantsChelation therapySignificant patientFamily burdenSubstantial burdenPatient experiencePatientsSemi-structured interview formatTherapyComplicationsResultsFour themesBurdenInformed decision-making process