Armando Hasudungan
Biology and Medicine videos

Acute Lymphoblastic Leukaemia

Overview

Overview Acute Lymphoblastic Leukaemia (ALL) is a malignancy of lymphoid cells. The two main ALL is T-cells ALL and B-cells ALL. In ALL there is uncontrolled proliferation of immature lymphoblasts in the bone marrow leading to overcrowding affecting other cell lineage. It is the commonest cancer in childhood, rare in adults and has a strong associated with Down’s Syndrome.

Definition
Leukaemia: Group of malignant disorder, affecting the blood forming tissue of the bone marrow lymph system and spleen
Acute lymphoblastic leukaemia: Most common leukaemia affecting children. Characterised by lymphoblasts in peripheral blood smear (lower cytoplasmic-nucleus ratio)
Acute Myeloid leukaemia: More common in young adults, adults. Characterised by the development of immature myeloblasts in the bone marrow.
Down’s Syndrome: Trisomy 21, a genetic disorder. Children with Down syndrome (DS) have an increased risk of B-cell precursor acute lymphoblastic leukemia.
SUMMARY OF MAJOR LEUKAEMIA
Subtype Description Typical Group affects
Acute lymphoblastic leukaemia Blast cells on peripheral blood smear or bone marrow aspirate Children (53% <20yo)
Acute Myelogenous leukaemia Blast cells on peripheral blood smear or bone marrow aspirate; Auer rods on peripheral smear, Myeloperoxidase positive Adults
Chronic lymphoblastic leukaemia Clonal expansion of at least 5,000 B lymphocytes per μL (5.0 × 109 per L) in the peripheral blood Older adults (85% >65yo)
Chronic Myelogenous leukaemia Philadelphia chromosome (BCR-ABL1fusion gene) Adults

Haematopoesis

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Watch Video Haemtopoesis

Classification

ALL is classified based on 3 things:

  • Morphology – divided into L1, L2, L3 based on microscopic appearence (nucleus, vesicles)
  • Immunological markers – differentiate B and T cell ALL as both have different sets of CD markers
  • Cytogenetics – Chromosomal analysis, looks at mutations in genes which gives a prognostic value.
    • Good prognosis
    • Poor prognosis – Philadelphia chromosome
Philadelphia chromosome is a balanced translocation between chromosome 9 and 22 which leads to the formation of the BCR/ABL fusion gene. This chromosome is seen mainly in Chronic myeloid leukaemia and sometime in ALL. In ALL it signifies a poorer prognosis

Risk Factors

  • Radiation
  • Chemicals – Benzene
  • Infection – human T-cell lymphoma/leukemia virus-1 (HTLV-1)
  • Inherited syndromes
    • Down syndrome
    • Klinefelter syndrome
    • Fanconi anemia
    • Bloom syndrome
    • Ataxia-telangiectasia
    • Neurofibromatosis
  • Race/ethnicity – more commone in african americans
PROGNOSIS FEATURES IN CHILDHOOD ALL
Risk Factors Favourable Unfavourable
Age 1-10yo <1 or >10 yo
Gender Female Male
Race/ethnicity Caucasian, Asian Black, Hispanic
White blood cell count <50000/ul >50000/ul
Immunophenotype B-precursor T cell, Mature B cell
Genetic features Hyperdiploidy, Translocation (12:21) Philadelphia gene (9:22), Hypodiploidy
Extramedullary involvement No Yes

Signs and Symptoms

Initial presentation

  • Fever
  • Anorexia
  • Fatigue
  • Bone and joint pain especially lower extremities

Bone marrow Failure

  • Anaemia
  • Infections
  • Bleeding, brusing
  • Fatigue

Infiltration (extramedullary haemtopoesis)

  • Hepatomegaly
  • Splenomegaly
  • Lymphadenopathy
  • Superficial or mediastinal
  • Orchidomegaly
  • CNS involvement – Cranial nerve palsy

Differential Diagnosis

  • Acute Myelogenous Leukemia (AML)
  • B-Cell Lymphoma
  • High-Grade Malignant Immunoblastic Lymphoma
  • Mantle Cell Lymphoma
  • Non-Hodgkin Lymphoma

Investigations

  • Full Blood Count – ↓Hb, thrombocytopaenia
  • Blood Smear – reveals lymphoblasts
  • Chest X-ray and CT scan – check for chest involvement
  • Lumbar puncture – check for CNS involvement

Management

Chemotherapy Program

  • Remission Induction – destroys 99% of “cancerous” cells
  • Consolidation – destroys further 99% of “cancerous” cells
  • CNS and Orchid prophylaxis – IV or intrathecal methotrexate
  • Maintenance – continuation of chemo up to 2 years – destroys remaining 99% of “cancerous” cells just to be sure
Side note Haemotological remission means no presence of lymphoblasts on peripheral blood smear, normal bloods and <5% blasts in regenerating bone marrow

 

Complications and Prognosis

Complications

  • Pancytopaenia
  • Febrile neutropenia
  • Pneumocystis carinii pneumonia and other infections
  • Tumour lysis syndrome
  • Chemotherapy adverse effects
    • Gastrointestinal
    • Alopecia (hair problem)
    • CNS toxicity
  • Avascular necrosis
  • Vincristine-related neuropathy
  • Relapse (increased ICP or isolated cranial nerve involvement)
Remember Patient with cancer with recent chemotherapy (white cell count significantly down) spikes serious fever give antibiotic – Tazocin

Prognosis

  • Good in children. Adults not as good

Acute Lymphoblastic Leukaemia and Acute Myeloid leukaemia

DIFFERENCES BETWEEN ACUTE MYELOID  LYMPHOBLASTIC LEUKAEMIA
Acute Myeloid Leukaemia Acute Lymphoblastic Leukaemia
Blast size on blood smear Medium to large, uniform Variable small to medium
Cytoplasm Fine granules maybe present Usualyl scant, a few coarse granules may be seen (morphology L3 – eosinophilic like)
Auer rods Present Absent
Nuclear chromatin Finely Dispersed Fine to corase
Genetic markers Myeloid peroxidase present (only found in myeloid cells) TDT marker present (only found in lymphoblasts)