Leukemia: ALL, AML, Classification, Prognosis, HSCT

Incidence · Classification (FAB, WHO) · Clinical presentation · Diagnosis · Morphology (blasts, Auer rods) · Prognostic indicators (cytogenetics, MRD) · Treatment (chemotherapy, HSCT) · Clinical trials
🩸 Key concepts: ALL most common childhood cancer (80%), B-ALL, T-ALL, AML (20%). Risk stratification by cytogenetics (hyperdiploid, ETV6-RUNX1, KMT2A, BCR-ABL, FLT3). Minimal residual disease (MRD) guides therapy. HSCT for high-risk/relapsed.

📖 Leukemia: classification, risk groups, treatment & HSCT

🧬 Incidence & Classification
ALL 80% of childhood leukemias (peak 2-5y). AML 20% (infants, adolescents). FAB classification (L1-L3; M0-M7). WHO integrates immunophenotype, cytogenetics, molecular.
🩺 Presentation & Diagnosis
Pallor, bruising, fever, bone pain, hepatosplenomegaly, lymphadenopathy. CBC: pancytopenia or WBC elevated with blasts. Bone marrow aspirate >20-25% blasts. Auer rods → AML.
📊 Prognostic Indicators
Age (1-10y favorable), WBC (<50,000 favorable), cytogenetics (hyperdiploid, ETV6-RUNX1 good; KMT2A, BCR-ABL, hypodiploid poor), MRD (minimal residual disease) after induction.
💊 Treatment (ALL)
Induction (vincristine, steroids, asparaginase, daunorubicin). CNS prophylaxis (intrathecal methotrexate). Consolidation, maintenance (2-3 years). Risk-adapted therapy. Clinical trials (UKALL, AIEOP-BFM).
🩸 AML & HSCT
AML: intensive chemotherapy (cytarabine + anthracycline). Gemtuzumab (CD33), FLT3 inhibitors. HSCT (allogeneic) for high-risk AML (MRD+, poor-risk cytogenetics, relapsed). HSCT also for high-risk ALL (BCR-ABL, induction failure).
⚠️ Leukemia mimics: ITP (isolated thrombocytopenia), aplastic anemia (pancytopenia, no blasts), juvenile idiopathic arthritis (bone pain, normal CBC), EBV infection.

🩺 Diagnostic approach to suspected leukemia

1
History & physical – Pallor, fatigue, fever, bone pain (night pain, limping), easy bruising/bleeding, lymphadenopathy, hepatosplenomegaly, mediastinal mass (T-ALL).
2
Initial labs – CBC with differential (blasts, cytopenias). Peripheral smear. LDH, uric acid, electrolytes, coagulation profile.
3
Bone marrow aspirate & biopsy – Morphology (blast percentage, Auer rods), immunophenotyping (flow cytometry: CD19, CD10, CD34, TdT for B-ALL; CD3, CD7 for T-ALL; myeloid markers CD13, CD33, MPO for AML).
4
Cytogenetics & molecular – Karyotype, FISH, RT-PCR for prognostic markers (ETV6-RUNX1, BCR-ABL, KMT2A, hyperdiploid, hypodiploid). MRD by flow or PCR at day 28.
5
CNS involvement – Lumbar puncture (day 1 of therapy). CSF cytospin for blasts.
📌 Clinical pearl: Auer rods (reddish needle-like inclusions) are pathognomonic for AML. T-ALL often presents with mediastinal mass, respiratory distress.

📋 Stepwise management of childhood leukemia & HSCT

1
Supportive care at diagnosis – Tumor lysis prophylaxis (allopurinol/rasburicase, hydration). Transfusions (irradiated, leukodepleted). Fever/neutropenia → IV antibiotics. Avoid steroids before diagnosis (masking).
2
ALL induction therapy – Vincristine, prednisolone/dexamethasone, L-asparaginase, daunorubicin (risk-adapted). Intrathecal methotrexate (CNS prophylaxis). Remission rate >95%.
3
ALL risk-adapted post-induction – Consolidation (high-dose methotrexate, 6-MP), delayed intensification, maintenance (2-3 years). Target MRD-negative status. BCR-ABL (Ph+) ALL add tyrosine kinase inhibitor (imatinib/dasatinib).
4
AML treatment – Intensive cytarabine (Ara-C) + anthracycline (daunorubicin/idarubicin) + etoposide. Gemtuzumab ozogamicin (CD33). FLT3 inhibitors (midostaurin). CNS prophylaxis (intrathecal).
5
Hematopoietic stem cell transplant (HSCT) – Indications: high-risk AML (MRD+, poor cytogenetics, secondary AML), high-risk ALL (induction failure, persistent MRD, BCR-ABL, hypodiploid), relapsed leukemia. Allogeneic (matched sibling/unrelated).
6
Clinical trials – UKALL (ALL), AML trials (NOPHO, COG). Novel agents: CAR-T cells (tisagenlecleucel for B-ALL), blinatumomab (BiTE), inotuzumab (CD22).
🚨 Emergency: hyperleukocytosis (WBC >200,000) – Risk of leukostasis (neurologic, respiratory). Consider leukapheresis, hydration, low-dose chemotherapy. Avoid transfusion if possible (increases viscosity).

🧠 Reflex prompts: leukemia, AML, HSCT

🩸 4-year-old with pallor, bruising, bone pain, WBC 35,000 with 40% blasts. Most likely diagnosis?
Acute lymphoblastic leukemia (ALL), B-cell precursor. Bone marrow, immunophenotyping.
🔬 Peripheral smear shows Auer rods. Which leukemia?
Auer rods are pathognomonic for acute myeloid leukemia (AML).
🧬 Which cytogenetic abnormality confers favorable prognosis in childhood ALL?
High hyperdiploid (>50 chromosomes) and ETV6-RUNX1 (t(12;21)).
📉 Minimal residual disease (MRD) after induction therapy: significance?
MRD >0.01% indicates higher risk of relapse; used to intensify therapy (HSCT).
🩸 A 2-year-old with ALL, WBC 400,000, respiratory distress. Immediate risk?
Leukostasis (sludging). Urgent leukapheresis, hydration, cytoreduction.
💊 What is the standard CNS prophylaxis in ALL?
Intrathecal methotrexate ± cytarabine, plus systemic high-dose methotrexate (risk-adapted).
🩸 Which tyrosine kinase inhibitor is used for Philadelphia chromosome-positive (BCR-ABL) ALL?
Imatinib or dasatinib combined with chemotherapy.
🧬 Indications for allogeneic HSCT in childhood ALL?
High-risk features: induction failure, persistent MRD, hypodiploidy, BCR-ABL, relapsed ALL.
🩺 Most common childhood leukemia?
B-cell precursor acute lymphoblastic leukemia (B-ALL) ~75-80% of all leukemias.
🩸 What is the role of CAR-T therapy (tisagenlecleucel) in ALL?
CD19-directed CAR-T cells for relapsed/refractory B-ALL (after ≥2 lines).