Acute Lymphoblastic Leukemia

Definition

A cancer of the blood and bone marrow characterized by the overproduction of immature lymphoid cells (lymphoblasts). It’s the most common childhood cancer, but it can also occur in adults.

Pathophysiology

ALL arises from a mutation in lymphoid precursor cells (either B or T cells) in the bone marrow. These abnormal lymphoblasts proliferate rapidly and crowd out normal blood cell production (RBCs, WBCs, platelets).

Epidemiology

• Most common in children ages 2–5
• Less common in adults but with worse prognosis

Symptoms

Due to bone marrow failure and organ infiltration:

• Anemia → fatigue, pallor
• Neutropenia → frequent infections
• Thrombocytopenia → bleeding, bruising
• Bone pain, especially in long bones
• Lymphadenopathy, hepatosplenomegaly
• CNS symptoms (e.g., headache, vomiting) if CNS is involved

Diagnosis

• CBC: ↑ WBCs (may be normal or low), ↓ Hb, ↓ platelets
• Peripheral smear: Lymphoblasts
• Bone marrow biopsy: >25% lymphoblasts confirms diagnosis
• Immunophenotyping (flow cytometry): B-cell or T-cell markers
• Cytogenetics: Look for chromosomal abnormalities (e.g., Philadelphia chromosome in adults)

Prognosis

• Children: ~80–90% cure rate
• Adults: ~30–40% survival (worse if Ph+ or older age)

Treatment

• Induction chemotherapy (e.g., vincristine, corticosteroids, anthracyclines)
• CNS prophylaxis (e.g., intrathecal methotrexate)
• Consolidation & maintenance therapy
• Stem cell transplant in high-risk or relapsed cases

 Treatment of Acute Lymphocytic Leukemia (ALL)

Treatment is divided into phases, and each phase has a specific goal. The full treatment can last 2–3 years, especially in children.

1. Induction Therapy

Goal: Achieve complete remission (i.e., <5% blasts in bone marrow, normal blood counts).

Duration: ~4 weeks

Common Drugs (Regimen varies by risk group):

• Vincristine (microtubule inhibitor)
• Corticosteroids (prednisone or dexamethasone)
• Anthracyclines (e.g., daunorubicin)
• Asparaginase (especially in children)
• Add-on: Intrathecal chemotherapy (methotrexate ± cytarabine + hydrocortisone) for CNS prophylaxis.

2. Consolidation (Intensification) Therapy

Goal: Eliminate residual leukemic cells that remain after induction.

Duration: Several months

Common Drugs:

• High-dose methotrexate
• Cytarabine
• 6-mercaptopurine (6-MP)
• May repeat drugs from induction in higher doses

3. CNS Prophylaxis

Goal: Prevent or treat leukemic spread to the CNS.

Method:

• Intrathecal chemotherapy throughout all phases (methotrexate ± cytarabine ± steroids)
• Sometimes cranial radiation in high-risk or T-ALL (less common in children now due to long-term side effects)

4. Maintenance Therapy

Goal: Maintain remission and prevent relapse.

Duration: ~2 years (longer in children than adults)

Drugs:

• Oral 6-mercaptopurine (daily)
• Methotrexate (weekly)
• Vincristine (monthly)
• Steroids (5-day pulses monthly)

5. Allogeneic Stem Cell Transplant

Indicated for:

• High-risk patients (e.g., adverse cytogenetics, minimal residual disease)
• Adults with Philadelphia chromosome-positive (Ph+) ALL
• Relapsed/refractory ALL

6. Targeted Therapy

Used in specific genetic subtypes:

Monitoring Response:

• Bone marrow biopsy after induction
• Minimal Residual Disease (MRD) testing by flow cytometry or PCR
• Frequent CBCs, LFTs, renal function tests

Supportive Care:

• Antibiotics/antifungals for neutropenia
• Blood product transfusions
• Tumor lysis syndrome prevention (hydration, allopurinol or rasburicase)
• Psychosocial support, especially in pediatric patients

 

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