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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
Key points
- Acute leukemia presents with marrow failure: anemia, infections, thrombocytopenic bleeding, and circulating blasts
- AML is more common in adults; ALL is most common in children and can present with mediastinal mass if T-cell
- Auer rods indicate myeloid lineage; multiple Auer rods and DIC suggest acute promyelocytic leukemia
- APL is a medical emergency: start ATRA immediately if suspected because hemorrhagic DIC can be fatal
- Hyperleukocytosis with respiratory or neurologic symptoms = leukostasis; urgent cytoreduction is required
Overview
Acute leukemia is defined by expansion of immature hematopoietic blasts in marrow, blood, and sometimes extramedullary tissues. AML arises from myeloid precursors and is associated with Auer rods, myeloperoxidase positivity, prior chemotherapy, radiation, MDS, and older age. ALL arises from lymphoid precursors and is the most common childhood cancer; adults have worse outcomes.
Epidemiology
ALL peaks in childhood but also occurs in adults. AML incidence increases with age and is associated with prior cytotoxic chemotherapy, radiation, benzene exposure, smoking, myelodysplastic syndromes, Down syndrome, and inherited marrow failure syndromes. APL is a distinct AML subtype with PML-RARA translocation.
Clinical Features
Symptoms
Fatigue, dyspnea, pallor from anemia
Fever, recurrent infections, neutropenia
Easy bruising, petechiae, epistaxis, gum bleeding from thrombocytopenia
Bone pain, weight loss, night sweats
Dyspnea, headache, confusion, visual symptoms suggesting leukostasis
Bleeding with DIC suggesting APL
Signs
Pallor, petechiae, ecchymoses
Lymphadenopathy, hepatosplenomegaly, gingival hypertrophy or skin lesions in AML
Testicular enlargement or mediastinal mass in ALL
Retinal hemorrhages or neurologic deficits in leukostasis
Investigations
First-line
CBC with differential and smearBlasts, anemia, thrombocytopenia, neutropenia or leukocytosis; Auer rods in AML
Coagulation studies, fibrinogen, D-dimerEssential if APL suspected or bleeding; DIC is common in APL
CMP, uric acid, phosphorus, potassium, calcium, LDHAssess tumor lysis risk and organ function before therapy
Second-line
Flow cytometryDefines lineage: myeloid versus B-ALL/T-ALL and immunophenotype
Bone marrow biopsy and aspirateConfirms diagnosis and obtains cytogenetics/molecular testing
Chest imagingEvaluate mediastinal mass in suspected T-ALL and infection if febrile
Specialist
Cytogenetic and molecular testingAML: PML-RARA, FLT3, NPM1, CEBPA; ALL: BCR-ABL and risk stratification
Lumbar punctureCNS staging/prophylaxis in ALL after stabilization and platelet support
1
Immediate stabilization
- Admit urgently and involve hematology/oncology
- Neutropenic fever: immediate broad-spectrum antipseudomonal antibiotics
- Transfuse RBCs and platelets as needed; irradiated/leukoreduced products are commonly used
- Start tumor lysis prophylaxis with IV fluids and allopurinol or rasburicase when appropriate; avoid rasburicase in G6PD deficiency
2
Acute promyelocytic leukemia emergency
- Suspect APL with abnormal promyelocytes, Auer rods, bleeding, and DIC
- Start ATRA immediately before genetic confirmation if APL is suspected
- Aggressively support fibrinogen and platelets to reduce fatal hemorrhage
3
Definitive therapy
- AML: induction chemotherapy or lower-intensity venetoclax-based regimens depending on fitness and genetics
- ALL: multi-agent chemotherapy with CNS prophylaxis; add tyrosine kinase inhibitor for Philadelphia chromosome-positive ALL
- Consider allogeneic stem cell transplant in high-risk or relapsed disease
4
Leukostasis
- Respiratory or neurologic symptoms with very high WBC require urgent cytoreduction
- Hydroxyurea, leukapheresis in selected cases, and rapid initiation of disease-specific therapy
Complications
- Sepsis: Neutropenia and mucosal barrier injury
- DIC: Especially acute promyelocytic leukemia
- Tumor lysis syndrome: Hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, AKI
- Leukostasis: Pulmonary and CNS ischemia from hyperviscosity
- CNS disease: Particularly ALL
USMLE Step 2 CK Exam Tips
- 1Auer rods = AML; Auer rods plus DIC = APL, start ATRA now
- 2Pancytopenia with blasts = acute leukemia until proven otherwise
- 3Neutropenic fever: broad-spectrum antipseudomonal antibiotics immediately
- 4T-ALL can present with anterior mediastinal mass in adolescent male
- 5ALL is the most common childhood cancer
- 6Hyperleukocytosis + dyspnea/confusion = leukostasis, not simple anemia
- 7Tumor lysis: high K, high phosphate, low calcium, high uric acid
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