Leukemias

Leukemia Basics - Tiny Troublemakers

• Uncontrolled proliferation of abnormal white blood cells (WBCs) in bone marrow.
• "Liquid tumors" that crowd out normal blood cell production (anemia, infections, bleeding).
• Most common childhood cancer.
• Major Types:
  • Acute Lymphoblastic Leukemia (ALL): Most frequent (~75-80%). Peak: 2-5 yrs.
  • Acute Myeloid Leukemia (AML): Accounts for ~15-20%.

⭐ Down syndrome confers a 10-20 fold ↑ risk for developing acute leukemia (both ALL & AML).

ALL Unmasked - Lympho‑Blast Off!

• Most common childhood cancer; peak 2-5 yrs.
• Presentation: Fever, pallor, bleeding, bone pain. Lymphadenopathy, hepatosplenomegaly. CNS/testicular involvement possible.
• Diagnosis:
  • Bone Marrow: >25% lymphoblasts (WHO).
  • Immunophenotyping:
    • B-ALL (~85%): CD19, CD10 (CALLA), TdT+.
    • T-ALL (~15%): CD3, CD7, TdT+. Often mediastinal mass.
• Cytogenetics (Prognostic):
  • Good: Hyperdiploidy, t(12;21) [ETV6-RUNX1].
  • Poor: Hypodiploidy, t(9;22) [BCR-ABL1], MLL rearrangements (11q23).
• Crucial: CNS prophylaxis (intrathecal MTX) for all.

  ⭐ T-ALL often presents with a large anterior mediastinal mass causing respiratory distress or SVC syndrome.

ALL Combat Plan - Victory Blueprint

• Treatment Phases (Multi-agent Chemo):
  • Induction (VCR, Prednisolone, L-Asparaginase ± Daunorubicin): Achieve remission.
  • Consolidation: Eradicate residual cells.
  • Interim Maintenance.
  • Delayed Intensification.
  • Maintenance (6-MP, MTX): Total 2-3 yrs.
• CNS Prophylaxis: Mandatory; Intrathecal (IT) Methotrexate.
• NCI Risk Stratification (B-ALL):
  • Standard Risk (SR): Age 1-9.99 yrs & WBC < 50,000/µL.
  • High Risk (HR): Age <1 yr / ≥10 yrs or WBC ≥ 50,000/µL.
• Key Prognostic Factors:
  • Good: Age 1-9 yrs, WBC <50K, t(12;21) ETV6-RUNX1, hyperdiploidy.
  • Poor: Age <1 yr, Ph+ t(9;22) BCR-ABL1, MLL rearranged, hypodiploidy, CNS disease.

⭐ Minimal Residual Disease (MRD) status post-induction is the most powerful prognostic indicator in ALL.

AML Alert - Myeloid Mayhem

• Predominantly adults, but occurs in children; poorer prognosis than ALL.
• Diagnosis: >20% myeloblasts in bone marrow.
• Markers: Myeloperoxidase (MPO), Sudan Black B.
• 📌 Auer rods: Pathognomonic, especially in APL (M3).
• Clinical: Gingival hypertrophy, leukemia cutis, DIC (esp. APL).
• Key Cytogenetics:
  • APL (M3): t(15;17) (PML-RARA); treat with ATRA.
  • Good prognosis: t(8;21), inv(16).
  • Poor prognosis: Monosomy 5 or 7.

⭐ APL (Acute Promyelocytic Leukemia), a subtype of AML, is uniquely responsive to All-Trans Retinoic Acid (ATRA) therapy, which induces differentiation of leukemic promyelocytes.

Leukemia Crisis Mode - Code Red!

• Tumor Lysis Syndrome (TLS): Oncologic emergency from rapid cell death. Key labs: ↑K, ↑PO4, ↑Uric Acid, ↓Ca.
  • Management: Aggressive IV fluids, Allopurinol or Rasburicase.
  • Monitor: Strict I/O, electrolytes. Cairo-Bishop criteria for diagnosis.
• Hyperleukocytosis: Extreme WBC count >100,000/µL. High risk of leukostasis (CNS, respiratory distress).
  • Management: Urgent cytoreduction (Hydroxyurea, Leukapheresis), hydration.
• Febrile Neutropenia: Fever (T >38.3°C single, or >38°C for 1hr) + ANC <500/µL. Life-threatening!
  • Management: Immediate empiric broad-spectrum IV antibiotics.

⭐ Rasburicase is contraindicated in G6PD deficiency due to risk of hemolysis and methemoglobinemia.

High‑Yield Points - ⚡ Biggest Takeaways

• ALL is the most common childhood malignancy; peak incidence 2-5 years.
• Good prognostic factors in ALL: Age 1-9 years, WBC < 50,000/μL, t(12;21).
• Poor prognostic factors in ALL: Age <1yr/>10yrs, WBC >50,000/μL, t(9;22) (Philadelphia), MLL gene.
• CNS prophylaxis (intrathecal chemotherapy) is crucial in ALL.
• AML: Auer rods are pathognomonic. APL (M3) with t(15;17), treat with ATRA; risk of DIC.
• Down syndrome confers ↑ risk of ALL and AML (especially megakaryoblastic).