Multidimensional Flow Cytometry Significantly Improves Upon the Morphologic Assessment of Post-Induction Marrow Remission Status – Comparison of Morphology and Multidimensional Flow Cytometry; A Report From the Children9s Oncology Group AML Protocol AAML0531

Abstract 939 Initial response to induction chemotherapy is a significant predictor of outcome in leukemias, where those with rapid response have an improved outcome compared to the non-responders. Morphologic evaluation of post induction marrow has been the gold standard in assessing remission status in leukemias, where those with 15% blasts were considered to be high risk. The Children9s Oncology Group (COG) phase III AML protocol AAML0531 which treated 1022 eligible patients without Down Syndrome (DS) on an MRC based chemotherapy backbone, utilized the >15% post induction morphologic blast threshold, as assessed at the institutional level, to allocate patients to specific risk groups based on the observed post induction 1 blast prevalence. In this study, all patients regardless of initial response would receive a second course of similar induction chemotherapy. Those with 5–15% blasts after course 1 with no other risk features who achieved a CR after the second course were considered intermediate risk, but those with >15% post course 1 blasts who achieved a CR after course 2 were considered high risk and allocated to stem cell transplantation from the most suitable donor in first CR. As part of this trial, multidimensional flow cytometry (MDF) was used to assess marrow response after each course of induction chemotherapy. As morphologic evaluation would not be able to distinguish normal and malignant blasts in the marrow, we inquired whether morphologic CR status correlates with MDF findings. Of the 1022 eligible non-DS patients treated on AAML0531, 784 patients had consented to the correlative biology studies and had available MDF data for correlation with morphology. Of the 784 patients, 185 patients (24%) had failed to achieve a morphologic CR (>5% blast by morphology) after the initial course of chemotherapy, of which 94 were partial remissions (PR, 5–15% blast) and 91 were persistent disease (PD, >15%). Of these 185 patients who failed to achieve a morphologic CR, 67 patients (36%) had no evidence of disease by MDF, and the remaining 64% had MDF detectable disease. Clinical outcome evaluation of these patients who failed induction (>5% blast) at the end of course 1 based on MDF status demonstrated that disease free survival for those with MDF detectable disease was 24% compared to that of 52% in those with induction failure with no MDF detectable disease (p 15% blast after course I, 25 (27%) had no evidence of disease by MDF. Disease-free survival at 3 years from end of induction in this high risk cohort with and without MDF-detectable disease was 20% and 55%, respectively (p Disclosures: Smith: Seattle Genetics: ; Eisai: ; Archimedes Pharma: Membership on an entity9s Board of Directors or advisory committees; Pfizer, Inc.: Membership on an entity9s Board of Directors or advisory committees.