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 motifsReproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation
George S, Veludhandi A, Xiang Y, Liu K, Stenger E, Arnold S, Mehta A, Schirmer D, Spencer J, Guilcher G, Bhatia M, Abraham A, Gomez-Lobo V, Krishnamurti L, Meacham L. Reproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation. Transplantation And Cellular Therapy 2024, 30: 912.e1-912.e13. PMID: 38972510, PMCID: PMC11344653, DOI: 10.1016/j.jtct.2024.06.029.Peer-Reviewed Original ResearchHematopoietic cell transplantationSickle cell diseaseFollicle-stimulating hormone levelsPost-HCTParent-proxyConditioning regimensCell transplantationFertility counselingHormone levelsCell diseaseCyclophosphamide equivalent doseSickle cell disease patientsPremature ovarian insufficiencyElevated FSH levelsDiminished ovarian reserveAnti-Mullerian hormone levelsBone marrow stem cellsEffective method of educationGonadal hormone productionHealth Survey dataReproductive health assessmentReproductive health issuesMarrow stem cellsSibling donorOvarian insufficiencyHigh-impact chronic pain in sickle cell disease: insights from the Pain in Sickle Cell Epidemiology Study (PiSCES)
Jagtiani A, Chou E, Gillespie S, Liu K, Krishnamurti L, McClish D, Smith W, Bakshi N. High-impact chronic pain in sickle cell disease: insights from the Pain in Sickle Cell Epidemiology Study (PiSCES). Pain 2024, 165: 2364-2369. PMID: 38787626, PMCID: PMC11404329, DOI: 10.1097/j.pain.0000000000003262.Peer-Reviewed Original ResearchHigh-impact chronic painSickle Cell Epidemiology StudyChronic painProportion of daysUS National Pain StrategySickle cell diseaseNational Pain StrategySelf-care activitiesEpidemiological studiesHigher levels of stressMean pain intensityCohort of individualsPain interferenceLevels of stressPhysical functionHealth outcomesHealthcare utilizationPhysical healthPain strategiesPain burdenPain intensityPain diaryCell diseaseDiary daysAffected subgroupsIncidence and risk factors of pain crisis after hematopoietic cell transplantation for sickle cell disease
Krishnamurti L, Liang J, He Z, Deng Y, Nallagatla V, Hamidi R, Flagg A, Shah N. Incidence and risk factors of pain crisis after hematopoietic cell transplantation for sickle cell disease. Blood Advances 2024, 8: 1908-1919. PMID: 38324722, PMCID: PMC11021890, DOI: 10.1182/bloodadvances.2023010749.Peer-Reviewed Original ResearchHematopoietic cell transplantationSickle cell diseaseVaso-occlusive episodesPainful crisesCell transplantationPost-HCTGraft failureBefore HCTEvent-free survivalOverall survivalPain syndromePatient agePatient-centered outcomesAlternative donorsIncreased riskCell diseaseRisk factorsNatural historyPatientsLogistic regressionPainTransplantationSurvivalAgeAGVHDComparison of Outcomes of Hematopoietic Cell Transplantation (HCT) for Asymptomatic Patients with Sickle Cell Disease (SCD) and That of Propensity Matched Symptomatic Patients Undergoing HCT
Katoch D, Nallagatla V, Liang J, Deng Y, Krishnamurti L. Comparison of Outcomes of Hematopoietic Cell Transplantation (HCT) for Asymptomatic Patients with Sickle Cell Disease (SCD) and That of Propensity Matched Symptomatic Patients Undergoing HCT. Transplantation And Cellular Therapy 2024, 30: s65. DOI: 10.1016/j.jtct.2023.12.103.Peer-Reviewed Original ResearchHematopoietic cell transplantationOutcomes of hematopoietic cell transplantationSickle cell diseaseSymptomatic SCD patientsAsymptomatic patientsDonor typeSymptomatic patientsPost-HCTSCD patientsHematopoietic cell transplantation comorbidity indexPost-transplant lymphoproliferative disorderMedian follow-up periodComplication of sickle cell diseaseIncidence of aGVHDReduced intensity conditioningSickle cell disease patientsFollow-up periodPropensity-matched modelStandardized mean differenceSecondary malignanciesLymphoproliferative disordersCell transplantationGraft survivalPatient ageAssociated with group classificationDevelopment of a Prototype Clinical Decision Support Tool for a Machine Learning Based Individualized Prediction of Outcomes of Hematopoietic Cell Transplantation for Sickle Cell Disease
Subramaniam R, Kane M, Krishnamurti L. Development of a Prototype Clinical Decision Support Tool for a Machine Learning Based Individualized Prediction of Outcomes of Hematopoietic Cell Transplantation for Sickle Cell Disease. Transplantation And Cellular Therapy 2024, 30: s65-s66. DOI: 10.1016/j.jtct.2023.12.104.Peer-Reviewed Original ResearchHematopoietic cell transplantationOutcomes of hematopoietic cell transplantationSickle cell diseasePositive predictive valueDecision support toolMachine-learningClinical decision support toolCell transplantationBalanced accuracyGraft failureSupport toolFold cross validationDecision-making methodPositive outcomesPredictive valueGVHD prophylaxis regimensEvent-free survivalBinary classifierUser inputRelevant clinical parametersReceiver operating characteristic curvePrototype decision support toolTraining datasetOperating characteristics curveTest datasetPreservation of Pulmonary Function Following Hematopoietic Cell Transplant for Sickle Cell Disease: A STAR Study
Horan F, Bendiak G, Abraham A, Liu K, Gillespie S, Chellapandian D, Shah R, Bhatia M, Chaudhury S, Eckrich M, Jaroscak J, Kasow K, Krajewski J, Ngwube A, Horan J, Krishnamurti L, Shenoy S, Guilcher G, Stenger E. Preservation of Pulmonary Function Following Hematopoietic Cell Transplant for Sickle Cell Disease: A STAR Study. Transplantation And Cellular Therapy 2024, 30: s45-s46. DOI: 10.1016/j.jtct.2023.12.079.Peer-Reviewed Original ResearchHematopoietic cell transplantationPulmonary function testsPost-HCTYears post-HCTSickle cell diseaseAmerican Thoracic SocietyCell transplantationPulmonary dysfunctionPulmonary functionCurative hematopoietic cell transplantationPreservation of pulmonary functionCell diseaseGroup of SCD patientsPulmonary function test dataPost-HCT patientsProgressive pulmonary dysfunctionLung volume valuesSevere clinical phenotypeMyeloablative conditioningMedian followHLA matchingMedian ageNo significant differencePFT resultsPre-HCTDecreasing alloimmunization‐specific mortality in sickle cell disease in the United States: Cost‐effectiveness of a shared transfusion resource
Ito S, Pandya A, Hauser R, Krishnamurti L, Stites E, Tormey C, Krumholz H, Hendrickson J, Goshua G. Decreasing alloimmunization‐specific mortality in sickle cell disease in the United States: Cost‐effectiveness of a shared transfusion resource. American Journal Of Hematology 2024, 99: 570-576. PMID: 38279581, DOI: 10.1002/ajh.27211.Peer-Reviewed Original ResearchSickle cell diseaseDelayed hemolytic transfusion reactionQuality-adjusted life expectancyAlloimmunized patientsPatient populationRed blood cell alloimmunizationCell diseaseCost-effective interventionMedical expenditure of patientsHealth system perspectiveExpenditure of patientsIncremental cost-effectiveness ratioHemolytic transfusion reactionsUnited StatesMarkov cohort simulationCost-effectiveAverage patient populationCost-effectiveness ratioBirth cohortAnalytical time horizonAntibody historyCohort simulationTransfusionTransfusion reactionsLife expectancy
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 trialRegimen Intensity and Age Affect Transplant-Related Outcomes after Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Registry Study
John T, Chellapandian D, Shah R, Gillespie S, Liu K, Xiang Y, Bhatia M, Chaudhury S, Eckrich M, Guilcher G, Jaroscak J, Kasow K, Krajewski J, Ngwube A, Olson T, Rangarajan H, Horan J, Krishnamurti L, Shenoy S, Abraham A, Stenger E. Regimen Intensity and Age Affect Transplant-Related Outcomes after Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Registry Study. Blood 2023, 142: 4904. DOI: 10.1182/blood-2023-182532.Peer-Reviewed Original ResearchHematopoietic cell transplantationRejection-free survivalAnti-thymocyte globulinSickle cell diseaseRelated donor hematopoietic cell transplantationDonor hematopoietic cell transplantationBu/CyShorter hospital stayCumulative doseSevere GVHDHospital stayOverall survivalCell transplantationCell diseaseDay 5Grade III/IVBu/cyclophosphamideBu/FluUse of alemtuzumabKaplan-Meier methodCurrent clinical trialsRisk of rejectionSmall cohort sizeSevere clinical phenotypeConditioning chemotherapyStandardized Clinical Pathways Improve Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department
Forward J, Thomas D, O'Malley S, Berkwitt A, Calhoun C, Krishnamurti L, Pashankar F. Standardized Clinical Pathways Improve Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department. Blood 2023, 142: 2315. DOI: 10.1182/blood-2023-181285.Peer-Reviewed Original ResearchVaso-occlusive episodesSickle cell diseasePediatric emergency departmentMinutes of arrivalPain managementEmergency departmentClinical pathwayIntranasal fentanylYears post implementationHydromorphone PCAPain medicationPediatric patientsJune 30 thPain medication administrationVaso-occlusive painPercent of patientsPercentage of patientsQuality improvement projectOutcome one yearElectronic medical recordsPost implementationHealth care systemFirst analgesicED visitsED encountersIndividualized Prediction of Outcomes of Hematopoietic Cell Transplantation for Sickle Cell Disease: A Machine Learning Approach
Subramaniam R, Kane M, Krishnamurti L. Individualized Prediction of Outcomes of Hematopoietic Cell Transplantation for Sickle Cell Disease: A Machine Learning Approach. Blood 2023, 142: 1058. DOI: 10.1182/blood-2023-178352.Peer-Reviewed Original ResearchIncorporation of uncertaintyModel selectionModel versatilityQuantifying uncertaintyML methodsHematopoietic cell transplantationSupervised random forest modelSuch modelsSickle cell diseaseThreshold δML modelsModel confidenceAverage probabilityMachine learning methodsIncorrect resultsPredictive model performancePositive predictive valueUnknown dataAcceptable AUCPredictive modelUncertaintyVariables of interestHigh accuracyArithmetic meanCell transplantationComparison of Outcomes of Hematopoietic Cell Transplantation (HCT) for Asymptomatic Patients with Sickle Cell Disease (SCD) and That of Propensity Matched Symptomatic Patients Undergoing HCT
Katoch D, Nallagatla V, Krishnamurti L. Comparison of Outcomes of Hematopoietic Cell Transplantation (HCT) for Asymptomatic Patients with Sickle Cell Disease (SCD) and That of Propensity Matched Symptomatic Patients Undergoing HCT. Blood 2023, 142: 3873. DOI: 10.1182/blood-2023-190977.Peer-Reviewed Original ResearchHematopoietic cell transplantationSickle cell diseaseComplications of SCDGraft failureOverall survivalAsymptomatic patientsAvascular necrosisSCD patientsDonor typeChronic GVHDCell transplantationCell diseaseOutcomes of HCTPost-transplant lymphoproliferative disorderSubstantial short-term morbidityCommon graft sourceExperienced graft failureHCT comorbidity indexAcute chest syndromeHLA-identical donorShort-term morbidityLong-term sequelaePotential curative optionSubset of patientsOrgan-specific complicationsAllotransplantation and Gene Therapy Equity for Children with Sickle Cell Disease: Distributional Cost-Effectiveness of Allotransplantation Vs Gene Therapy Vs Standard-of-Care in Pediatric Patients with Sickle Cell Disease in the United States
Goshua G, Ito S, Chetlapalli K, Potnis K, Calhoun C, Krishnamurti L, Krumholz H, Pandya A. Allotransplantation and Gene Therapy Equity for Children with Sickle Cell Disease: Distributional Cost-Effectiveness of Allotransplantation Vs Gene Therapy Vs Standard-of-Care in Pediatric Patients with Sickle Cell Disease in the United States. Blood 2023, 142: 490. DOI: 10.1182/blood-2023-191072.Peer-Reviewed Original ResearchSickle cell diseaseIncremental cost-effectiveness ratioDistributional cost-effectiveness analysisPediatric patientsCell diseaseCost-effectiveness analysisDisease severityHealth resource utilization dataPediatric Health Information SystemGene therapyJustifiable treatment optionTransplant-related mortalityVaso-occlusive crisisExpert clinical experienceMarrow Transplant ResearchSubstantial mortality riskVisual analog scaleQuality-adjusted life expectancyConcomitant riskCost-effectiveness ratioResource utilization dataCost-effectiveness frontierHost diseaseMaximum patientsOpioid therapyDonor Hemoglobin Genotype Does Not Impact Outcomes Following Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Study
Stenger E, John T, Chellapandian D, Shah R, Gillespie S, Xiang Y, Liu K, Bhatia M, Guilcher G, Jaroscak J, Kasow K, Krajewski J, Ngwube A, Rangarajan H, Horan J, Krishnamurti L, Shenoy S, Abraham A. Donor Hemoglobin Genotype Does Not Impact Outcomes Following Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Study. Blood 2023, 142: 4955. DOI: 10.1182/blood-2023-188514.Peer-Reviewed Original ResearchHematopoietic cell transplantationSickle cell diseaseDonor hematopoietic cell transplantationLong-term outcomesPost-HCTOrgan dysfunctionCell transplantationCell diseaseRelated donor hematopoietic cell transplantationSignificant differencesVaso-occlusive pain crisesComparable long-term outcomesLong-term outcome dataLast platelet transfusionMarkers of hemolysisCategorical variablesSymptom-free survivalSignificant organ dysfunctionHb AASickle cell traitContinuous variablesSevere clinical phenotypeSevere disease phenotypeChronic GVHDPain crisisAbatacept-Prophylaxis Based Haploidentical Transplantation May Allow Sustained Engraftment and Offset Gvhd in Non-Malignant Disorders
Ngwube A, Shah N, Schulz G, Krishnamurti L, Shenoy S. Abatacept-Prophylaxis Based Haploidentical Transplantation May Allow Sustained Engraftment and Offset Gvhd in Non-Malignant Disorders. Blood 2023, 142: 4901. DOI: 10.1182/blood-2023-191145.Peer-Reviewed Original ResearchNon-malignant disordersPost-transplant cyclophosphamideSickle cell diseaseGVHD prophylaxisHematopoietic transplantationEvaluable patientsHaploidentical transplantationImmune suppressionBone marrowFirst year post-HCTGrade 1 acute GVHDChronic GVHD riskChronic skin GVHDGVHD-free survivalPost-transplant lymphoproliferationsRadiation-containing regimensYear post-HCTPhase 2 trialReduced intensity conditioningSerious infectious complicationsSystemic immune suppressionT-cell chimerismAllogeneic hematopoietic transplantationPrimary outcome measureStem cell boostFemale 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 ResearchConceptsHematopoietic 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 participantsInfertility378 Main Reasons for Performing Hematopoietic Cell Transplantation in Patients with Sickle Cell Disease: Evolution over the Last Three Decades
Flagg A, He Z, Deng Y, Hamidi R, Shah N, Krishnamurti L. 378 Main Reasons for Performing Hematopoietic Cell Transplantation in Patients with Sickle Cell Disease: Evolution over the Last Three Decades. Transplantation And Cellular Therapy 2023, 29: s285-s286. DOI: 10.1016/s2666-6367(23)00447-5.Peer-Reviewed Original Research379 The Impact of Current Conditioning Regimen, T Cell Depletion and Graft Versus Host Disease Prophylaxis on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Disease
Shah N, Flagg A, Hamidi R, Hugo H, Deng Y, Krishnamurti L. 379 The Impact of Current Conditioning Regimen, T Cell Depletion and Graft Versus Host Disease Prophylaxis on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Disease. Transplantation And Cellular Therapy 2023, 29: s286-s287. DOI: 10.1016/s2666-6367(23)00448-7.Peer-Reviewed Original Research