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