SBIR/STTR Award attributes
Abstract Acute lymphoblastic leukemiaALLis the most common malignant disease in childhood and accounts for approximatelyof all cancers diagnosed before the age ofyearsThe primary cause of death for ALL patients is disease relapseThereforemonitoring for minimal residual diseaseMRDis considered the most powerful predictor of outcome in acute leukemiasincluding B type acute lymphoblastic leukemiaB ALLIf clinicians could identify a patient s MRD before the tumor cells rapidly expand to florid relapsepreemptive therapies could be undertaken with better patient outcomeFor pediatric B ALLthere are existing tests for monitoring relapse from MRD including PCR or multi parameter flow cytometrybut require a bone marrow aspiratewhich can be painful and limits the frequency of testingIf MRD could be detected in B ALL patients from peripheral blood and not bone marrowthe corresponding assay could assist in guiding therapy to enable precision medicine resulting in better patient outcomeIn this applicationan innovative test that consists of a microfluidic assay and the associated hardware will be developedThe test can provide high clinical sensitivity for MRD testing and permits frequent minimally invasive sampling using peripheral bloodmLas opposed to an invasiveespecially for pediatric patientsbone marrow biopsyThe assay uses a microfluidic device to analyze peripheral blood and search for circulating leukemic cellsCLCsUsing this microfluidic assay in a longitudinal study of acute myeloid leukemiaAMLpatients following stem cell transplantationMRD via monitoring of CLCs was detectedmonths earlier compared to both multi parameter flow cytometryMFCand PCRwhich used bone marrow aspiratesthe microfluidic assay wasorders of magnitude more sensitive than PCR and MFCOwing to the ability of the microfluidic assay to detect CLCs in bloodmore frequent testing of a patientsdisease status was possible when compared to bone marrow biopsy testingFor B ALLanti CDantibodies immobilized within a microfluidic device can affinityselect cells expressing CDsurface antigen commonly expressed by B ALL lymphoblastsi eCLCand normal B cellsCLCs are identified by expression of aberrant markerssuch as Terminal deoxynucleotidyl TransferaseTdTand the number of CLCs tracked to determine the onset of relapse or the risk of relapseIn this SBIR Phase I II fast track proposalthe CLC microfluidic test will be expanded and developed for commercialization to monitor MRD and potential relapse in B ALL pediatric patients to provide coverage ofGiven the strong data generated to date and the urgent diagnostic need for an improved easy to implement MRD assay for frequent monitoringthe proposed test fills an unmet clinical need in the area of pediatric oncologyAs a notethe test can be reprogrammed to search for other pediatric oncological diseases such as T cell ALLrequires only a change in the cell selection antibodyNarrative Acute lymphoblastic leukemiaALLis the most common malignant disease in childhood and accounts forof all cancers diagnosed before the age ofyearsThe primary cause of death for ALL occurs due to disease relapseMonitoring of minimal residual diseaseMRDis considered the most powerful predictor of outcome in acute leukemiasincluding B type acute lymphoblastic leukemiaB ALLIf clinicians could pinpoint when a patient s minimum residual diseaseMRDbegins rapid expansion to relapsepreemptive therapies can be taken to dramatically improve patient outcomeIn this Phase I II applicationa fully automated instrument that can process peripheral blood directlysearch for circulating leukemic cellsCLCsin pediatric ALL patientsand detect relapse earlier than current techniques will be developedThis application represents a significant improvement to standard of care that requires painful bone marrow aspirates in children to monitor MRD
