Acute Lymphoblastic Leukemia: Symptoms, Causes and Treatments

Acute Lymphoblastic Leukaemia is a malignant clone that arises from hematopoietic progenitors in bone marrow, resulting in an increase in immature, non-functioning leukemic cells.

Etiology

The etiology of acute leukemia is unknown; some external and internal factors influence the incidence of leukemia. The inheritance of certain diseases and exposure to ionizing radiation, chemicals, and chemotherapy is associated with an increased risk of leukemia developing. 

Clinical Features of Acute Lymphocytic Leukaemia

Commonly seen in children

• Lymphoblast is proliferating so much → other lineages are suppressed
  • Anemia
  • Fatigue
  • Tiredness
  • Pallor: Due to depletion in neutrophils, eosinophils, basophils, monocytes
  • Recurrent infections
  • Thrombocytopenia
  • Bleeding manifestations
• Organ involvement - (T- ALL - tissue infiltration)
  • Hepatosplenomegaly

Important Subtypes of ALL

• Common ALL: CD10 Marker : t(9:22) q 34:q11) del (6q) higher age >55 years
• Mature B ALL:  (t8:14 ) (q24,q32) (t2;8) ( p12;q24 )  (t8;22 ) (q 24;q11), higher age, frequent organ involvement
• T-Lineage ALL: Younger age, frequent mediastinal tumors, and CNS involvement with High WBC

ALL FAB: CLASSIFICATION

ALL-WHO classification

1. B - ALL (B for bachas - children)

• PAX5 - loss of function mutation
• E2A
• EBF
• Good prognosis

2. T - ALL (T for teenagers )

• Tissue infiltration
  • CNS
  • Mediastinum
  • Testes
• NOTCH mutation
• Poor prognosis

PAX5 gene - For B Cell Development

Loss of function mutation - lymphoblast do not mature → lymphoblastic leukemia

ALL – Genetics

Bcr-Abl fusion - t(9:22)

1. Philadelphia chromosome seen in :
   1. ALL: 190 Kd
   2. CML: 210 Kd
   3. CNL: 230 Kd (Chronic Neutrophilic Leukemia)
2. If Bcr- Abl fusion protein weighs
   1. 190 kD - ALL
   2. 210 kD -CML
   3. 230 kD -CNL
3. Lesser the weight of Bcr- Abl fusion protein → more is the tyrosine kinase activity → bad prognosis
4. ALL - bad prognosis- for t(9:22)

ALL – Diagnosis

• Peripheral blood & Bone marrow > 20%
• Stains of lymphoblasts
  • PAS positive + (Dot, blot, or block positivity)
  • T- ALL - acid phosphatase
• CD markers
  • To identify T / B lymphoblasts
• Flow cytometry- diagnosis of choice

Prognostic factors 

Risk Factors for developing Acute Leukaemia’s 

1. Congenital disorders: Klinefelter’s, Fanconi anemia, bloom syndromes, neurofibromatosis, ataxia telangiectasia.
2. Infectious agents: HTLV-1, EBV herpes DNA virus.

Treatment of ALL

1. Pediatric inspired therapies: Large cumulative dosages of drugs such as vincristine, L-Asparaginase & glucocorticoids.
2. Adult ALL: Chemotherapy regimen & stem cell transplantation
3. Elderly ALL: Palliative treatment or intensive chemotherapy has failed, low complete remission rates or high early death rates 
4. Maintenance Treatment: 6-Mercaptopurine & methotrexate from childhood
5. Prophylaxis of CNS leukemia: Cranial radiation therapy, Intrathecal therapy

Immunotherapeutic Drugs

• Anti-CD20 :Rituximab
• Anti CD 22 : Calicheamicin
• Anti CD-19 : Blinatumomab

Download the PrepLadder app now to access high-yield content with 24-hr Free Trial. Explore premium study resources like Video Lectures, digital notes, QBank, and Mock Tests for a seamless exam preparation. Start your NEET PG online coaching journey with PrepLadder.