Acute lymphoblastic leukemia (ALL)

Recognize it

• Weeks of fatigue, pallor, bruising or petechiae, bone pain (a limping child who refuses to walk), fever without a source.
• Exam: hepatosplenomegaly, diffuse lymphadenopathy, testicular enlargement in boys, anterior mediastinal mass in T-ALL.
• CBC classically shows anemia and thrombocytopenia; WBC can be low, normal, or extremely high — a normal WBC does not exclude ALL.
• Peripheral smear with blasts prompts urgent heme-onc referral; diagnosis requires ≥20% lymphoblasts on bone marrow aspirate with flow cytometry.
• Always include LP with intrathecal chemotherapy at diagnosis: CNS status (CNS1/2/3) changes therapy.

Stratify it

• NCI/Rome criteria on age and presenting WBC give the first split (standard vs high risk).
• Cytogenetics refine it: ETV6-RUNX1 and hyperdiploidy (>50 chromosomes, trisomies 4/10/17) are favorable; KMT2A (MLL) rearrangement in infants, hypodiploidy (<44), and TCF3-HLF are unfavorable.
• Ph-positive (BCR-ABL1) and Ph-like ALL get a tyrosine kinase inhibitor added to chemotherapy.
• End-of-induction minimal residual disease (MRD) by flow or PCR is the single most powerful prognostic variable and drives intensification.

Treat it (phases you will hear on rounds)

• Induction (~4 weeks): vincristine, corticosteroid (dexamethasone or prednisone), asparaginase ± anthracycline. Goal is morphologic remission.
• Consolidation / CNS-directed therapy: intrathecal methotrexate ± cytarabine; cranial radiation is now rare and reserved for CNS3 or relapse.
• Interim maintenance and delayed intensification: high-dose or escalating methotrexate, more asparaginase.
• Maintenance: daily 6-mercaptopurine, weekly oral methotrexate, vincristine/steroid pulses, ongoing intrathecal therapy.
• Immunotherapy for relapsed/refractory or high-MRD disease: blinatumomab (CD19 BiTE), inotuzumab (CD22), tisagenlecleucel (CD19 CAR-T).

Toxicities to anticipate by drug

• Vincristine: peripheral and autonomic neuropathy, constipation, jaw pain. FATAL if given intrathecally — never leave the syringe with the IT tray.
• Anthracyclines: cumulative cardiomyopathy; track lifetime dose, echo surveillance, dexrazoxane in some protocols.
• Asparaginase: hypersensitivity, pancreatitis, thrombosis (including sinus venous thrombosis), hypertriglyceridemia, hyperglycemia.
• High-dose methotrexate: mucositis, nephrotoxicity, delayed clearance — leucovorin rescue, urine alkalinization, avoid NSAIDs/TMP-SMX/PPIs per protocol; glucarpidase for true delayed clearance.
• Steroids: hyperglycemia, hypertension, mood and sleep disruption, avascular necrosis (especially adolescents), immunosuppression.
• 6-MP: hepatotoxicity and myelosuppression; TPMT/NUDT15 variants cause severe cytopenias — dose-reduce, do not just hold.

Pearls

• Bone pain that wakes a child at night plus cytopenias is leukemia until the marrow says otherwise.

  It is the classic shelf discriminator against juvenile idiopathic arthritis and growing pains.

• Down syndrome raises ALL risk ~10–20x and raises methotrexate toxicity — protocols are dose-modified.

• Blasts on the smear are not required for diagnosis; aleukemic presentations exist.

• Vincristine is a fatal-if-IT drug. It is dispensed in a mini-bag, never a syringe, for exactly that reason.

  This is a required safety answer, not trivia.

On the ward

1. 1Confirm weight and BSA are current — every dose is written on them.
2. 2Verify TLS labs are ordered q6–8h and that hydration is running without potassium.
3. 3Document CNS status from the diagnostic LP in the H&P; therapy depends on it.
4. 4Check that PJP prophylaxis (TMP-SMX) is on the med list before discharge.
5. 5Ask the family what they were told, in their words, before you add to it.

Sources

• Children's Oncology Group — Protocol families and risk stratification frameworks used across US pediatric centers.
• NCCN Guidelines (Pediatric) — US consensus guidance on treatment and supportive care pathways.