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 ResearchMeSH KeywordsAdultAnemia, Sickle CellAnimalsFemaleFetal HemoglobinGene EditingHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHumansMaleMiceRepressor ProteinsZinc Finger NucleasesConceptsHematopoietic 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
Female 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 ResearchMeSH KeywordsAdolescentAdultAnemia, Sickle CellChildFemaleFertility PreservationGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansInfertilityMiddle AgedParentsTransplantation ConditioningConceptsHematopoietic 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 ResearchMeSH KeywordsAnemia, Sickle CellCyclophosphamideGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansLeukemia, Myeloid, AcuteNeoplasms, Second PrimaryTransplantation ConditioningWhole-Body IrradiationConceptsLow-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 transplantationDecision-making about gene therapy in transfusion dependent thalassemia
Quarmyne M, Ross D, Sinha C, Bakshi N, Boudreaux J, Krishnamurti L. Decision-making about gene therapy in transfusion dependent thalassemia. BMC Pediatrics 2022, 22: 536. PMID: 36085025, PMCID: PMC9461218, DOI: 10.1186/s12887-022-03598-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlood TransfusionChildGenetic TherapyHematopoietic Stem Cell TransplantationHumansQuality of LifeThalassemiaConceptsTransfusion-dependent thalassemiaPatient/family knowledgeDependent thalassemiaTransfusion independenceTreatment optionsStudy participantsGene therapyFamily knowledgeElimination of transfusionsFrequency of transfusionMorbidity/mortalityStem cell transplantationLong-term outcomesPreferred treatment modalityPromising treatment optionBackgroundHematopoietic stem cell transplantationPatients/familiesMethodsParents of childrenCurative intentTransfusion reductionHost diseaseDonor HSCTParents of childrenCell transplantationMean age
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 ResearchMeSH KeywordsAnemia, Sickle CellClinical Decision-MakingDonor SelectionGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansTransplantation ConditioningConceptsHematopoietic 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 registryHematopoietic 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 statusGaps 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
Primary 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 ResearchMeSH KeywordsAdultAnemia, Sickle CellAutograftsBenzylaminesBlood Component RemovalBone MarrowCyclamsFemaleGenetic TherapyHematopoietic Stem Cell MobilizationHematopoietic Stem Cell TransplantationHeterocyclic CompoundsHumansMaleMiddle AgedShould 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 ResearchMeSH KeywordsAnemia, Sickle CellChild, PreschoolHematopoietic Stem Cell TransplantationHumansMaleQuality of LifeSiblingsTissue DonorsTransplantation ConditioningConceptsHematopoietic 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 ResearchMeSH KeywordsAllograftsAnemia, Sickle CellChildFemaleHematopoietic Stem Cell TransplantationHumansMaleConceptsHematopoietic cell transplantationSickle cell diseaseCell transplantationCell diseaseOrgan dysfunctionSCD patientsSignificant morbidityEarly mortalityClinical trialsAvailable cureSCD recipientsAlternative donorsIndividual patientsClinical practicePatientsTransplantationClinical vignettesDiseaseOutcomesMorbidityDysfunctionMortalityTrialsRecipients
2017
Bone 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
2016
Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation
Gluckman E, Cappelli B, Bernaudin F, Labopin M, Volt F, Carreras J, Pinto Simões B, Ferster A, Dupont S, de la Fuente J, Dalle J, Zecca M, Walters M, Krishnamurti L, Bhatia M, Leung K, Yanik G, Kurtzberg J, Dhedin N, Kuentz M, Michel G, Apperley J, Lutz P, Neven B, Bertrand Y, Vannier J, Ayas M, Cavazzana M, Matthes-Martin S, Rocha V, Elayoubi H, Kenzey C, Bader P, Locatelli F, Ruggeri A, Eapen M. Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood 2016, 129: 1548-1556. PMID: 27965196, PMCID: PMC5356458, DOI: 10.1182/blood-2016-10-745711.Peer-Reviewed Original ResearchConceptsEvent-free survivalSickle cell diseaseGraft failureCell transplantationHLA-identical sibling transplantationReduced-intensity conditioning regimensHLA-identical sibling transplantsHematopoietic stem cell transplantationMyeloablative conditioning regimenHematopoietic cell transplantationStem cell transplantationCox regression modelMarrow Transplant ResearchBenefit of transplantStem cell sourceSibling transplantationConditioning regimenPrimary endpointConditioning regimensMost patientsOverall survivalSibling transplantsCurative therapyInternational BloodMedian ageHaematopoietic stem cell transplantation for sickle cell disease – current practice and new approaches
Arnold S, Bhatia M, Horan J, Krishnamurti L. Haematopoietic stem cell transplantation for sickle cell disease – current practice and new approaches. British Journal Of Haematology 2016, 174: 515-525. PMID: 27255787, DOI: 10.1111/bjh.14167.Peer-Reviewed Original ResearchMeSH KeywordsAnemia, Sickle CellDisease-Free SurvivalGenetic TherapyHematopoietic Stem Cell TransplantationHLA AntigensHumansUnrelated DonorsConceptsHaematopoietic stem cell transplantSickle cell diseaseCell diseaseAllogeneic haematopoietic stem cell transplantOnly available curative therapyHaematopoietic stem cell transplantationAlternative donor transplantsAvailable curative therapyCurrent maintenance therapiesTransplant-related mortalityDisease-free survivalIncidence of rejectionStem cell transplantStem cell transplantationHuman leucocyte antigenPool of donorsComplications persistHaploidentical donorsMaintenance therapyConditioning regimensCurative optionDonor transplantsSibling transplantsSupportive careCurative therapyGonadal shielding technique to preserve fertility in male pediatric patients treated with total body irradiation for stem cell transplantation
Sayan M, Cassidy R, Butker E, Nanda R, Krishnamurti L, Khan M, Esiashvili N. Gonadal shielding technique to preserve fertility in male pediatric patients treated with total body irradiation for stem cell transplantation. Bone Marrow Transplantation 2016, 51: 997-998. PMID: 26950374, DOI: 10.1038/bmt.2016.25.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentChildChild, PreschoolFertilityHematopoietic Stem Cell TransplantationHumansInfantMaleMutationOrgan Sparing TreatmentsRadiation ProtectionSpermatogenesisTestisTreatment OutcomeWhole-Body Irradiation
2015
Mesenchymal stromal cells to modulate immune reconstitution early post-hematopoietic cell transplantation
Stenger E, Krishnamurti L, Galipeau J. Mesenchymal stromal cells to modulate immune reconstitution early post-hematopoietic cell transplantation. BMC Immunology 2015, 16: 74. PMID: 26674007, PMCID: PMC4681052, DOI: 10.1186/s12865-015-0135-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClinical Trials as TopicGraft SurvivalHematopoiesisHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHumansImmunomodulationMesenchymal Stem Cell TransplantationMesenchymal Stem CellsModels, AnimalConceptsHematopoietic cell transplantationMesenchymal stromal cellsCell transplantationPost-hematopoietic cell transplantationStromal cellsHematopoietic stem cell engraftmentPre-clinical studiesStem cell engraftmentHost diseaseImmune reconstitutionClinical trialsAnimal modelsCell engraftmentMultipotent progenitor cellsImmune systemHSC engraftmentCellular therapyProgenitor cellsTransplantationEngraftmentTrialsDual effectCellsEarly evidenceGVHDIndications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease
Walters M, De Castro L, Sullivan K, Krishnamurti L, Kamani N, Bredeson C, Neuberg D, Hassell K, Farnia S, Campbell A, Petersdorf E. Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease. Transplantation And Cellular Therapy 2015, 22: 207-211. PMID: 26500093, PMCID: PMC5031360, DOI: 10.1016/j.bbmt.2015.10.017.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnemia, Sickle CellChildHematopoietic Stem Cell TransplantationHistocompatibility TestingHumansQuality of LifeRisk FactorsSiblingsTransplantation ConditioningConceptsHematopoietic cell transplantationSickle cell diseaseCell transplantationCell diseaseSurvival rateEvent-free survival rateTransplant-related complicationsOverall survival rateMarrow Transplant RegistryMarrow Transplant ResearchRisk of mortalityLong-term qualityRate of survivalNontransplant cohortHost diseaseTransplant RegistryOverall survivalProspective trialInternational BloodTransplant ResearchEuropean BloodMortality riskSuitable donorTherapeutic valueStrong recommendations