ACUTE Leukemia

What Is Leukemia?• Cancer of the white blood cells• Acute or Chronic• Affects ability to produce normal blood cells• Bone marrow makes abnormally large number of immature white

blood cells called blasts

History• Means “white blood” in Greek• Discovered by Dr. Alfred Velpeau in France, 1827• Named by pathologist Rudolf Virchow in Germany, 1845

Main Types• Acute Lymphocytic Leukemia (ALL)• Acute Mylogenous Leukemia (AML)• Chronic Lymphocytic Leukemia (CLL)• Chronic Mylogenous Leukemia (CML)

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Classification of Leukaemia• Acute• Chronic

• Myeloid• Lymphoid

Demographics of Leukemia Patients (2001 Data)

ALL11%

CLL26%

AML31%

CML15%

others17%

Total Reported Cases = 31,500Sources from Leukemia, Lyphoma, Myeloma Facts 2001

CLL=Chronic Lymphocytic

ALL=Acute Lymphocytic

CML=Chronic Mylogenous

AML=Acute Mylogenous

Symptoms• When there are excessive white blood cells --> Infections• When there are few red blood cells: Paleness --> Anemia• When there are few platelets --> Excessive bleeding

Tests For Diagnosis• Finger prick• Blood sample• Blood dye• Bone marrow sample• Spinal Tap/Lumbar Puncture

Pictures Of Blood

Normal human blood

White Cell Red Cell

Platelet

Blood with leukemia

BlastsRed Cell

Platelet

White Cell

Sources from Arginine.umdnj.eduSources from beyond2000.com

Effects On the Body• Attacks the immune system• Infections• Anemia• Weakness• No more regular white blood cells, red blood cells, and

platelets• Blasts clog blood stream and bone marrow

Development of Leukemia in the Bloodstream

Stage 1- Normal Stage 2- Symptoms Stage 3- Diagnosis

Stage 4- Worsening

Stage 5a- Anemia

Stage 5b- Infection

Legend

White Cell Red Cell Platelet Blast Germ Sources from Leukemia, by D. Newton and D. Siegel

Causes• High level radiation/toxin exposure• Viruses• Genes• Chemicals• Mostly unknown

Treatment• Chemotherapy• Immunotherapy• Radiation• Bone marrow transplant

ACUTE LEUKAEMIA

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• Rapidly progressive• Proliferation of primitive “blast” cells• Acute myeloblastic (myeloid) leukaemia

• “Acute non-lymphoblastic leukaemia”

• Acute lymphoblastic leukaemia

CLINICAL PRESENTATION

Symptoms of acute leukaemia are largely the result of interference with normal haematopoiesis.

Generally it is not possible on clinical presentation to differentiate lymphoid from myeloid leukaemia.

Causes of Acute Leukemias• Idiopathic (most)• underlying hematologic disorders• chemicals, drugs• ionizing radiation• viruses (Human T Lymphotropic Virus I)• hereditary/genetic conditions• Preceding bone marrow disorders• Chemotherapy – especially alkylating agents, epipodophyllotoxins and

anthracyclines

CLINICAL SIGNSpallorlymphadenopathyhepatosplenomegalysternal tendernesspurpura / petechiaeretinal haemorrhagesmouth ulcersgum hypertrophy (monocytic type)

LABORATORY FINDINGS

Hb is invariably low (30-80 g/L)

WBC is usually high (especially lymphoblastics and monocytics). Can be normal or low.

Plts usually dangerously low

Generally it is not possible to differentiate myeloblasts from lymphoblasts by morphology alone.

MANAGEMENT

Cytotoxic chemotherapy, radiotherapy and bone marrow transplantation. The goal is to eradicate the leukaemic cell mass while giving supportive care. In children with ALL postremission therapy includes central nervous system (CNS) prophylaxis.

PROGNOSIS

Young patients do better than old. Patients presenting with low white counts do better. Must achieve complete remission (no signs of leukaemia and return of normal haematology parameters) to prolong survival.

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Acute Lymphoblastic Leukaemia• WHO classification:

• Precursor B cell ALL• Precursor T cell ALL• Burkitt’s mature B lymphoblastic leukaemia/lymphoma• Bi-phenotypic leukaemia

• FAB• L1, L2, L3

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Epidemiology of ALL

• Peak incidence in children aged 4 years

• Rising incidence in old age

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Prognostic factors in ALL• Sex: female > male• Ethnicity: caucasian > non-caucasian• Age: <10 and >1 year old• WBC < 50 x 109/l• CNS involvement is bad• Initial response to treatment (day 14 BM)• Morphological and genetic sub-types

Clinical features of ALL• Bone pain – children• CNS involvement• Lymphadenopathy

Continue…• Involvement of other tissue such as spleen, liver, lymph node, and

meninges are common• Involvment of CNS may give rise to headach, vomiting and irritable

behaviour.

Principles of Treatment• combination chemotherapy

• first goal is complete remission• further Rx to prevent relapse

• supportive medical care• transfusions, antibiotics, nutrition,

metabolic /electrolyte abnormalities• psychosocial support

• patient and family

Therapeutic Concepts in ALL• Induce a complete remission and restore normal

hematopoiesis avoiding excessive toxicity• Reduce inapparent leukemia with short-term, high-

dosage cytocidal therapy early in remission when the child is well and drug sensitivity is greatest

• Prevent CNS leukemia• Use prolonged combination chemotherapy to

eradicate residual disease when there is no evidence of leukemia

Basic Therapy in Childhood ALL

• Induction Treatment 4-8 wk• Consolidation treatment (intensification) 2-10 wk• Continuation treatment (maintenance) 2-3 y• Reinduction therapy (delayed intensification) 2-7 wk• CNS-directed therapy (intrathecal injection of methotrexate

and cranial radiation) 3 wk