Katelyn Williams, MD and Nathaniel J. Silvestri, MD fromJohns Hopkins Hospital discuss the initial presentation and workup of acute lymphoblastic leukemia. Acute lymphoblastic leukemia (ALL) is the most commonpediatric cancer. Early recognition and prompt workup are critical for improvedoutcomes. A case-based conversation featuring a 5-year-old withfatigue, bone pain, pallor, and reduced activity, guided by pediatric hematology/oncology expert input. The discussion outlines red flags, initial laboratory tests, imaging, differential diagnoses, and referral pathways. Key points: Red flags for ALL in children include persistent bone/backpain, refusal to bear weight, unexplained bruising, pallor, and diminishedactivity. Comprehensive physical exam should assess forhepatosplenomegaly, lymphadenopathy, and, in boys, testicular involvement. Initial laboratory workup (if malignancy is suspected) centers on CBC with differential and reticulocyte count, with attention to red cell indices (MCV, iron studies), hemoglobin, platelets, and neutrophils; LDH and uric acid; CMP and coag studies; and peripheral smear. WBC counts can be normal, low, or high at presentation;imaging (e.g., chest X-ray) is considered to evaluate potential mediastinal mass, particularly with risk for T‑cell leukemia. Differential includes infectious diseases and rheumatologicconditions; neuroblastoma should be considered in the differential of bone pain. Referral to pediatric oncology or the emergency departmentis advised when alarm features or concerning labs are present. Management considerations in the ED/outpatient settinginclude non-emergent procedures planning, NPO status when needed, and cautious use of steroids due to risks such as tumor lysis and diagnostic masking. Resources and collaboration with oncology, vaccinationconsiderations during therapy, and family education are emphasized. Implications: The talk reinforces recognizing early ALLsigns, initiating appropriate labs and imaging, timely referrals, and coordinated care to optimize outcomes.
