Hematology Oncology · Year 2 · from Hematology Oncology

Case 3: Acute Lymphoblastic Leukemia (ALL)

Patient Presentation

Demographics: 6-year-old male

Chief Complaint: Bone pain, fatigue, and fever for 2 weeks

History of Present Illness: The child has been complaining of leg and back pain for 2 weeks, refusing to walk at times. He has had decreased energy and appetite. His parents noticed he appears paler than usual and has had fevers up to 38.5C. He has had a few nosebleeds and bruises easily. His teacher noted he has been less active at school.

Physical Examination:

  • Vital signs: BP 100/60, HR 110, RR 22, Temp 38.2C
  • General: Pale, irritable child preferring to lie still
  • HEENT: Conjunctival pallor
  • Lymph nodes: Cervical, axillary, and inguinal lymphadenopathy (1-2 cm nodes)
  • Cardiac: Tachycardic, grade II/VI flow murmur
  • Lungs: Clear
  • Abdomen: Hepatomegaly (4 cm), splenomegaly (5 cm)
  • Extremities: Tenderness to palpation over tibias and femurs
  • Skin: Scattered petechiae and ecchymoses

Workup and Results

Complete Blood Count:

  • WBC: 45,000/uL
  • Differential: 82% blasts
  • Hemoglobin: 6.8 g/dL
  • Platelets: 22,000/uL

Peripheral Blood Smear:

  • Numerous small to medium blasts
  • High nuclear-to-cytoplasmic ratio
  • Scant agranular cytoplasm
  • No Auer rods

Bone Marrow Biopsy:

  • 95% blasts replacing normal hematopoiesis
  • Flow cytometry: CD19+, CD10+, CD22+, TdT+, CD34+, CD20 (dim)
  • Cytoplasmic IgM negative
  • Myeloid markers negative

Cytogenetics/Molecular:

  • Hyperdiploidy (54 chromosomes) - favorable
  • ETV6-RUNX1 fusion: Negative
  • BCR-ABL: Negative
  • MLL rearrangement: Negative

Lumbar Puncture:

  • No blasts in CSF (CNS negative)
  • CSF WBC 2, protein 25, glucose 62

Chest X-ray:

  • No mediastinal mass (rules out T-ALL)

Clinical Image

Peripheral blood smear in acute lymphoblastic leukemia showing lymphoblasts with high nuclear-to-cytoplasmic ratio, scant agranular basophilic cytoplasm, and fine chromatin pattern without Auer rods.

Diagnosis

B-Cell Acute Lymphoblastic Leukemia - Standard Risk

Classification:

  • B-ALL (CD19+, CD10+, TdT+)
  • Age 1-9 years (favorable)
  • WBC <50,000/uL (favorable)
  • Hyperdiploidy (favorable cytogenetics)
  • CNS negative
  • Standard risk by NCI criteria

Treatment Plan

  1. Induction (4 weeks):
  • Prednisone or dexamethasone
  • Vincristine weekly
  • Asparaginase (PEG-asparaginase)
  • Daunorubicin (if higher risk)
  • Intrathecal methotrexate for CNS prophylaxis
  1. Consolidation:
  • Multiple cycles with rotating drug combinations
  • High-dose methotrexate
  • Continued intrathecal therapy
  1. Maintenance (2-3 years total therapy):
  • Daily 6-mercaptopurine
  • Weekly oral methotrexate
  • Monthly vincristine and steroid pulses
  1. Monitoring:
  • Minimal residual disease (MRD) assessment
  • End-induction MRD is strongest prognostic factor
  • TPMT testing for 6-MP dosing
  1. Prognosis:
  • Standard-risk pediatric B-ALL: >90% cure rate
  • Favorable cytogenetics (hyperdiploidy) improves outcomes

Teaching Points

  1. ALL is the most common childhood malignancy, peak incidence ages 2-5 years
  2. Bone pain is common in children with ALL due to marrow expansion
  3. B-ALL (85%) vs T-ALL (15%) distinguished by immunophenotype
  4. CD19+, CD10+ (CALLA), TdT+ defines precursor B-ALL
  5. Risk stratification includes age, WBC, cytogenetics, and MRD response
  6. CNS prophylaxis with intrathecal chemotherapy is mandatory in ALL
  7. Maintenance therapy for 2-3 years distinguishes ALL treatment from AML
  8. Pediatric-inspired regimens improve adult ALL outcomes

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