ACUTE LYMPHOBLASTIC

LEUKEMIA (ALL)

Definition
Leukemia: Uncontrolled neoplastic
proliferation of hematopoietic cells in
the bone marrow.
Acute: based on presentation i.e early
onset, presents early and may die
early.
First disseminated cancer shown to be
curable and as such has represented the
model malignancy for the principle of
cancer diagnosis, prognosis and

Epidemiology

It is the second most common

childhood cancer in Kenya after
Burkitt lymphoma
Leukaemia account for about 20% of
peadiatric malignancies in Kenya
with ALL being 68% of this.
It has a striking peak incidence
between 2-6years of age and occurs
slightly more frequently in boys than
in girls.

Etiology

Etiology is unknown.
Several genetic and environmental
factors are associated with
childhood leukemia:

Genetic conditions:

Down syndrome
Turner syndrome
Fanconi syndrome
Neurofibromatosis
Bloom syndrome
Ataxia telangiectasia
Diamond blackfan anaemia
Severe combined immune deficiency
Schwachman syndrome
Paroxysmal nocturnal hamoglobinuna
Kleinfelters syndrome
Li freumeni syndrome

Environmental factors

Ionizing radiation
Drugs
Alkylating agents
Nitrosourea
Epipodophyllotoxin
Benzene exposure
Advanced maternal age

Pathogenesis

The classification of ALL depends on

characterizing the malignant cell in
the bone marrow to determine the
morphology, phenotypic
characteristics as measured by cell
membrane markers, and cytogenetic
and molecular genetic features.
Morphology alone is usually
adequate for diagnosis, the others
are for disease classification and
prognosis and choice appropriate

FAB classification

L1 Lymphoblast are predominantly small, with

little cytoplasm
L2 Larger and pleomorphic with increased
cytoplasm, irregular nuclear shape and
prominent nucleoli
L3 finely stippled and homogeneous nuclear
chromatic, prominent nucleoli and deep blue
cytoplasm with prominent vacuolization. Also
known as Burkitt leukaemia one of the most
rapidly growing cancer in humans.
85% of ALL derived from progenitors of B celli
and about 15% are derived from T cells and
about 1% are derived from B cell (relatively
mature)
Chromosomal abnormalities are found in most
patients with ALL.

Clinical manifestations

Initial presentation is usually nonspecific and has been present for a

short while (4wks)
Anorexia
Fatigue
Irritability
Low-grade fever
Patients often have a history of an
upper respiratory tract infection in
the proceeding 1-2 months. Some
may have a skin rash.

Clinical manifestations

For the few who present later, symptoms

are predominantly localised to the bones
or joints, and may include joint swelling
There may also be abdominal discomfort.
As the disease progresses, signs and
symptoms of bone marrow failure become
obvious
Pallor and fatigue anaemia
Bruising and epistaxis thrombocytopenia
Fever (neutropenia, malignancy) - 25%
may be due to and infection such as URTI
or otitis media

On examination

Pallor
Purpuric and petechial skin lesions
Mucous membrane hemorrhage
Lymphadenopathy
Splenomegaly
Hepatomegaly (less common)
Tenderness on bone palpation
Joint swelling and effusion

Rarely, sign of intracranial pressure,

such as headache and vomiting,
indicate leukaemic meningeal
involvement - (Meningeal
lymphomatosis) so have papilledema,
cranial nerve palsies, seizures, nuchal
rigidity.
Hyperviscosity syndrome may occur.
Respiratory distress usually related
to anaemia but may occur due to
mediastinal mass of lymphoblasts.
Seen typically in adolescent boys with

Diagnosis
1) Diagnostic tests
Full blood count
Hb- anemia
WBC counts. May be raised, normal
or decreased. Majority of patients
have a WBC count of less than
10,000/mm3
Platelets thrombocytopenia (some
pts () have level >100,000/mm3

Peripheral blood film

Usually reported as atypical
lymphocytes. These are blasts in
circulation
Bone Marrow Aspirate
Leukemic lymphoblasts
Occasionally BMA may be hypocellular
do biopsy.
ALL is diagnosed by bone marrow cells
being 25% lymphoblast

Other diagnostic tests

Cytochemical staining
To differentiate from AML
Type of
PAS
Sudan
Lysozyme
leukemia
black/
esterase
Peroxidas
e
ALL
++
AML

+++

Cell markers (flow cytometry)

To further classify into B cell, T cell or
Pre B
Surface markers e.g.
B cells: TdT, CD34, CD20, CD24, CD10.
T cell: CD7, CD2, CD5.
CD10 is also known as common ALL
antigen (CALLA) Good prognosis.
Cytogenetics
Chromosomal alterations e.g.

2. Tests for disease

burden and spread

Chest x-ray check for mediastinal

mass.
CSF Lymphoblasts and CSF
leukocyte count increased.
Bone radiographs may show
altered medullary trabeculae,
cortical defects or subepiphyseal
bone resorption
Biochemistry- LDH levels.

3. Investigations for
therapy or treatment.

LFTs
U/E/C
Septic screening

Differential diagnosis

Acute myeloblastic leukemia

Subcutaneous nodules or
blueberry muffin lesions
Infiltration of the gingiva and
parotid gland (uncommon)
Signs and lab findings of DIC (esp.
acute promyelocytic leukemia)
Discrete masses chloromas or
granulocytic sarcomas

Other DDX

Juvenile rheumatoid arthritis

Rheumatic fever
Infections mononucleosis
Leukemoid cxn in fnfxns. Tb, Histoplasmosis,
granulomelons disease
Pertussis
Acute hemolytic syndrome
Sickle cell disease
Disease associated with BM failure.
Malignant neuroblastoma,
rhabdomyosarcona, Ewing sarcoma,
retinoblatorw
NonMalignant Aplastic anaemia

Treatment

Supportive
Definitive; chemotherapy and
irradiation

Supportive care

Family and patient counselling. This

include disease aetiology, treatment
design and cost, treatment side effect
(and associated complication) and
prognosis
Screening and management of infections.
Third generation cephalosporins singly or
in combination with an aminoglycoside
Pain control. Start with NSAIDs
morphine is the ultimate (Addiction
unwarranted if rx is of short period of
time)

Anti-emetics; Use plasil

(metochlopromide), Phenergan
(promethazine) dexamethasone or
Motilium singly or in combination.
Ondansetron or tropisetron (5HT
receptor antagonists) severe emesis
either singly or in combination with
dexamethasome or plasil
Haematological support; With
exception of vincnistine, prednisone and
L-asparaginars, all other cytotoxic drugs
cause myelosuppression. Total neutrophil
count below 100,/mm3 Hb <9g/dI, and

Education rehabilitation long

duration of hospitalization
Nutritional support
Management of metabolic
complication; Tumor lysis syndrome:
Hypocalcaemia,Hyperuricemia (give
allopunnol 10mg/kg/day (bd or TID)
Maximum of 200mg TID) hyperkalemia
and Hyperphosphatemia

Investigations before
treatment

LFTs
U/E/C
Septic screening

Chemotherapy
Patients are divided into
1. low risks
2. high risk
According to age, wbc count and
response to initial steroid therapy.

Risk groups
Low Risk

High Risk

AGE

2-10YRS

<2yrs and
>10yrs

WBC
COUNT

<
20,000/mm

>20000/mm

INITIAL
RESPONSE
TO
STEROID
THERAPY

Good (< 1000 Poor (>1000

blasts/mm)
blasts/mm)


1.
2.
3.
4.

Treatment is divided into :

Remission induction
Consolidation
CNS prophylaxis
Maintenance

Induction

Start prednisone tabs 60mg/m2 (as TID)

after diagnosis and give for one week than
assess total blast count. Allopurinol is
commenced at least 24 hours before and
IT cystosar (cytosine arabinoside) or
methotraxate given during diagnostic LP.
Tabs prednisone-3 weeks then tail down.
IV vincristine- 4 weeks
IV adriamycin- 4 weeks(Omit adnamycin
in low risk disease)
IT methotrexate or cytosar weekly for 4
weeks

If CNS disease is present, alternate

IT methotrexate and cytostar
weekly for total of 10 doses then
monthly IT adding hydrocortisone
for 6 months

Consolidation (Two
courses 7-10 days apart)

IV cyclophosphamide -single dose

IV cytosar- once daily for 4 days
6 mercaptopunne- once daily for 4
weeks
Bone marrows aspirate to assess
remission status before
commencement of maintenance
therapy. If not in remission, repeat a
third course of consolidation

Cranial irradiation

Maintenance

Monthly (2yrs)
Vincristine
6 mercaptopurine
Methotrexate
Prednisone
Doses of 6mp or MTX may be
adjusted upward or downwards to
maintain leucocytes counts between
1500-3500

Maintenance

3 monthly (1 year)
Adnamycin
Cyclophosphomide

Relapse

Usually those with T cell type.

The bone marrow is the most
common site of relapse, although
almost any site can be affected.
Extramedullary sites, - Most
common CNS and testes.
Treatment of testes- Testicular
irradiation. chemo should be
reinforced for patients who are still
undergoing rx or reinstituted for
those who have a relapse after

Prognosis

Treatment is the single most

important prognostics factor. The
earlier the better.
Other than these are Age <2 >10yrs, Initial leucocyte count >20,000/mm poor prognosis.
CALLA good prognosis.
Philadelphia chromosomes poor
prognosis. And other translocatinspoor prognosis