What Is B-Cell Acute Lymphoblastic Leukemia (B-ALL)?

B-ALL is a type of acute leukemia that arises from lymphoid stem cells in the bone marrow.
 In B-ALL:

• Immature B-cells (lymphoblasts) multiply uncontrollably
• They crowd out normal blood-forming cells
• They can spill into the bloodstream
• They may spread to lymph nodes, liver, spleen, and the central nervous system

This leads to low blood counts (anemia, low platelets, low immunity) and a range of symptoms.

Causes & Risk Factors

The exact cause of B-ALL is usually unknown. However, research shows links with:

Genetic Factors

• Mutations in lymphoid stem cells
• Chromosome abnormalities (e.g., BCR-ABL1)
• Inherited syndromes (Down syndrome, Fanconi anemia)

Environmental Factors

• Previous exposure to high radiation
• Exposure to certain chemicals (rare and poorly proven)

Medical History

• Previous chemotherapy or radiation for another cancer

Immune System Conditions

• Rare immune deficiency syndromes

Most cases, however, occur without any clear trigger.

Symptoms of B-ALL

Symptoms usually appear suddenly, often over days to weeks.

Blood-related Symptoms

• Fatigue, weakness
• Pale skin (anemia)
• Shortness of breath
• Frequent infections
• Fever without clear cause

Bleeding Symptoms

• Easy bruising
• Bleeding gums
• Frequent nosebleeds
• Red skin spots (petechiae)

Bone Marrow Symptoms

• Bone pain (especially legs, hips)
• Joint pain
• Back pain

Other Symptoms

• Enlarged lymph nodes
• Liver or spleen enlargement
• Loss of appetite
• Weight loss
• Night sweats
• Headache or neurological changes (if CNS involved)

When Should You Consider Evaluation for B-ALL?

Early diagnosis dramatically improves survival.
 You should consult a hematologist if any of these warning signs appear:

1. Persistent Fever for More Than 2 Weeks

Especially if accompanied by fatigue or infections.

2. Unusual or Rapid Bruising/Bleeding

• Nosebleeds
• Gum bleeding
• Red spots on skin

These often indicate low platelets.

3. Continuous Fatigue, Paleness, or Breathlessness

Common early signs of anemia from bone marrow failure.

4. Severe Bone or Joint Pain

Especially in children (leg pain is common).

5. Swollen Lymph Nodes

Neck, armpits, groin, or abdomen.

6. Abnormal CBC Report

If a routine blood test shows:

• Low hemoglobin
• Low platelets
• High or low WBC
• Blast cells

Evaluation is urgent.

7. Children Becoming Irritable, Tired, or Refusing to Walk

Often an early sign of bone marrow infiltration.

8. Patients Previously Treated With Chemo/Radiation

They need quick evaluation for new symptoms.

How Is B-ALL Diagnosed?

Diagnosis is multi-step and precise.

1. Complete Blood Count (CBC)

Shows:

• Low hemoglobin
• Low platelets
• Abnormal WBC count
• Presence of blasts

2. Peripheral Blood Smear

Examines blood under microscope.

3. Bone Marrow Aspiration & Biopsy

The confirmatory test.
 Helps determine:

• Blast percentage
• Immaturity of cells
• Disease subtype

4. Flow Cytometry

Identifies B-cell markers:

• CD19
• CD10
• CD22
• CD34
• TdT

This differentiates B-ALL from T-ALL or other cancers.

5. Cytogenetic & Molecular Testing

Critical for treatment planning.
 Tests for:

• BCR-ABL1 (Philadelphia chromosome)
• TEL-AML1 fusion
• Hyperdiploidy
• IKZF1 deletion
• KMT2A rearrangements

These define risk category and predict outcomes.

6. Lumbar Puncture

Checks if leukemia has spread to brain/spinal fluid.

7. Imaging

Ultrasound or CT if organ enlargement suspected.

Types of B-ALL

1. Standard-risk B-ALL

Favorable genetics and good response to treatment.

2. High-risk B-ALL

Genetic mutations, high WBC, or poor early response.

3. Philadelphia Chromosome-Positive (Ph+ B-ALL)

Caused by BCR-ABL1 fusion gene; needs targeted therapy.

4. Philadelphia-Like B-ALL (Ph-Like)

High-risk subtype resembling Ph+ B-ALL but without BCR-ABL1.

5. Early Pre-B / Pre-B / Mature B-ALL

Defined by stage of B-cell development.

Treatment of B-ALL

Treatment is long-term and delivered in phases.
 For children: 2–3 years
 For adults: Intensive shorter protocols + maintenance

Phase 1: Induction Therapy (First 4 Weeks)

Goal → Achieve complete remission (CR) by eliminating visible leukemia cells.

Includes:

• Vincristine
• Steroids (Prednisone/Dexamethasone)
• Asparaginase
• Anthracyclines (Daunorubicin)

Success rate: 80–95% remission in children, 70–85% in adults.

Phase 2: Consolidation / Intensification Therapy

Goal → Kill residual leukemia cells not visible in tests.

Drugs used:

• High-dose Methotrexate
• Cytarabine
• Cyclophosphamide
• Thioguanine
• Etoposide

Patients are monitored for toxicity, infections, and organ function.

Phase 3: CNS-Directed Therapy

Leukemia can hide in the brain and spine.
 So, CNS prophylaxis is mandatory.

Methods:

• Intrathecal chemotherapy (Methotrexate/Cytarabine)
• Occasionally low-dose cranial radiation (rare today)

Phase 4: Maintenance Therapy

Goal → Prevent relapse.
 Duration → 18–24 months

Medicines:

• 6-Mercaptopurine
• Methotrexate
• Periodic Vincristine & Steroids

Advanced & Targeted Therapies

a. Tyrosine Kinase Inhibitors (for Ph+ B-ALL)

TKIs target BCR-ABL1.

Examples:

• Imatinib
• Dasatinib
• Ponatinib

These dramatically improve survival.

b. Immunotherapy

1. Blinatumomab (BiTE Therapy)

Redirects T-cells to kill leukemia cells.
 Very effective for:

• Minimal residual disease (MRD)
• Relapsed B-ALL

2. Inotuzumab Ozogamicin

An antibody-drug conjugate targeting CD22.

When Is CAR-T Cell Therapy Considered in B-ALL?

CAR-T cell therapy (CD19-directed) is considered when:

1. Disease is Refractory (Not Responding to Chemotherapy)

CAR-T offers high remission rates even when chemo fails.

2. Relapse After Initial Treatment

Especially early relapse within 2 years.

3. Relapse After Stem Cell Transplant

One of the strongest indications for CAR-T.

4. Persistent MRD After Multiple Treatments

Even small traces of leukemia can cause relapse.

5. High-Risk Genetics

Ph-like or KMT2A rearrangements may benefit from early CAR-T.

6. Patient Not Fit for Intensive Chemotherapy

CAR-T is a strong option for medically fragile patients.

Bone Marrow Transplant (BMT)

BMT is recommended for:

• High-risk B-ALL
• Persistent MRD
• Relapsed disease
• Poor induction response
• Ph+ B-ALL with suboptimal TKI response

Transplant types Dr. Bhargava performs:

• Matched sibling
• Matched unrelated donor
• Haploidentical (half-matched)

Prognosis and Survival

Prognosis depends on:

• Age
• Molecular subtype
• Early treatment response
• MRD status
• Overall health

Children:

Very good prognosis → Cure rates 80–90%

Adults:

Moderate prognosis → Cure rates improving due to:

• TKIs
• Blinatumomab
• Inotuzumab
• CAR-T
• Advanced transplant techniques