## 2 Case Presentation  
An 18-year-old female presented to the emergency room at our hospital with one week of progressive fatigue and pallor. Her medical history included irregular menstrual periods and psychiatric diagnoses for which she took concomitant medications. She initially presented to a mobile clinic where a CBC was drawn, showing severe anemia. She was referred to the nearest pediatric emergency center, where a repeat CBC was significant, for a total WBC of \(24.37\times 10^{3}/\mu\)L with a monocytic predominance (45%) and no blasts present by automatic differential; hemoglobin of 5.8 g/dL; and platelet count of \(30\times 10^{3}/\mu\)L. An initial packed red blood cell (PRBC) transfusion was given with no significant increase in Hgb (post-transfusion Hgb of 6.0 g/dL). Her reticulocyte count, mean corpuscular volume (MCV), unconjugated bilirubin, and lactate dehydrogenase (LDH) were elevated, suggestive of possible acute hemolysis. The leading differential diagnosis at the time was acute leukemia, an autoimmune etiology causing destructive cytoperias, or a viral/infectious process. A flow cytometry analysis of peripheral blood identified a large population of monocytes, but without significant immunophenotypic aberrancies. Three days after admission, a bone marrow biopsy and aspirate were performed. The anatomic pathology revealed 20.5% blasts with features of abnormal monoblasts, which appeared more immature with prominent nuclear folds and gray to basophilic cytoplasm (Figure 1). The flow cytometry showed increased monocytes (46%) with immunophenotypic aberrancies, including CD4 (brighter), CD16+56 (partial, bright), CD117 (partial), and CD2 (partial), and a loss of CD11b (Figure 2). These results were consistent with acute myeloid leukemia with monocytic differentiation. Figure 1: Bone marrow aspirate smears show increased leukemic blasts (20.5%). The blasts are medium to large sized with high N:C ratio, with round to irregular to slightly convoluted nuclear  
contours, and have a finely dispersed chromatin pattern and visible nucleoli with variably basophilic and rarely azurophilic granules; overall, the blasts have features of monoblasts (**A**) and promonocytes (blast equivalents (**B**). Occasional neutrophils are dysplastic with abnormal nuclear lobation and hypogranulation (**C**). The core biopsy shows leukemic blast infiltration (**D**); (**A**-**C**), Wright-Giemsa Stain, at 1000\(\times\); (**D**), Hematoxylin and Eosin stain, with a magnification of 400\(\times\). The patient was transferred from the satellite community campus to the main academic campus and was enrolled into the active Children's Oncology Group (COG) study for AML, AAML1831. She was randomized to Arm B with CPX-351 (Vyxeos; 60 mg/m\({}^{2}\) daunorubicin equivalents IV on days 1, 3, and 5) and gemutzumab ozogamicin (4.5 mg on day 6). A lumbar puncture on day 8 was consistent with the CNS1 status. On day 10 of therapy, the local cytogenetics studies with chromosome analysis showed an abnormal clone in 18 out of 20 cells characterized by a pericentric inversion of chromosome 2 at bands 2p23-q13. A fluorescence in situ hybridization (FISH) evaluation was performed using 13 probe sets for AML and MDS and revealed no evidence of abnormal signal patterns. At the same time, the results of her centralized molecular studies from the COG AAML1831 study showed no CEBP\(\alpha\) or NPM1 mutation, and a _FLT3_ internal tandem duplication (_FLT3_-ITD) with an allelic ratio of 0.62. Since the gilteritinib arm of the COG AAML1831 study was temporarily closed, she was taken off the protocol therapy the following day and started sorafenibib at 400 mg PO daily on days 11-31. On day 27 of Induction 1, the patient's primary oncologist was informed that the central lab's _FLT3_-ITD result was an error due to sample mix-up. At the end of Induction 1 (day 45), an institutional next-generation DNA/RNA sequencing panel run on the diagnostic bone marrow aspirate was performed, confirming no _FLT3_-ITD mutation.