Page 238 - Essential Haematology

224 / Chapter 17 Acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is caused by

Table 17.1 Classifi cation of acute
an accumulation of lymphoblasts in the bone
lymphoblastic leukaemia (ALL) according to
marrow and is the most common malignancy of
the World Health Organization (WHO)
childhood. classifi cation (modifi ed).
Precursor lymphoid neoplasms
B lymphoblastic leukaemia/lymphoma
Incidence and p athogenesis B lymphoblastic leukaemia/lymphoma, NOS
B lymphoblastic leukaemia/lymphoma with

The incidence of ALL is highest at 3 – 7 years
recurrent genetic abnormalities
with 75% of cases occurring before the age of
B lymphoblastic leukaemia/lymphoma with

6. There is a secondary rise after the age of 40 t(9; 22)(q34; q11.2); BCR - ABL1
years. Eighty - five per cent of cases are of B - cell B lymphoblastic leukaemia/lymphoma with

lineage and have an equal sex incidence; there is a t(v; 11q23); MLL rearranged
male predominance for the 15% of T - cell ALL B lymphoblastic leukaemia/lymphoma with
(T - ALL). t(12; 21)(p13; q22); TEL - AML1 ( ETV6 - RUNX1 )
The pathogenesis is varied. Certain germline B lymphoblastic leukaemia/lymphoma with

polymorphism in a group of genes mainly involved hyperdiploidy
in B - cell development (e.g. IKZF1) are more fre- B lymphoblastic leukaemia/lymphoma with
quent in patients with B - cell ALL (B - ALL) than hypodiploidy (hypodiploid ALL)
controls. Interestingly, IKZF1 is also deleted in the T lymphoblastic leukaemia/lymphoma
leukaemic cells in 30% of high risk B - ALL and 95%
of ALL BCR - ABL1 positive cases. In a proportion NOS, not otherwise specifi ed.
of cases the first event occurs in the fetus in utero ,

with a secondary event possibly precipitated by
infection in childhood (see Fig. 11.3 ). Th e fi rst
event is a translocation (e.g. t(12; 21)) or point

mutation. The second event involves genome - wide
nalling pathway is activated in most cases (see
copy number alterations, some of which encode for
below).
functions relevant to leukaemogenesis. This is dis-

cussed further in Chapter 11 . In other cases, the
disease seems to arise as a postnatal mutation in an Clinical f eatures
early lymphoid progenitor cell.
Clinical features are a result of the following.
Bone m arrow f ailure
Classifi cation
• Anaemia (pallor, lethargy and dyspnoea);
Acute lymphoblastic leukaemia, B cell or T cell,
• Neutropenia (fever, malaise, features of mouth,
is subclassified by WHO (2008) according to the

throat, skin, respiratory, perianal or other
underlying genetic defect (Table 17.1 ). Within
infections);
B - ALL there are several specific genetic subtypes

• Th rombocytopenia (spontaneous bruises,
such as those with the t(9; 22) or t(12; 21)
purpura, bleeding gums and menorrhagia).
translocations, rearrangements of the MLL gene
or alteration in chromosome number (diploidy)
(Table 17.1 ). The subtype is an important guide Organ i nfi ltration

to the optimal treatment protocol and to prog-
nosis. In T - ALL an abnormal karyotype is Tender bones, lymphadenopathy (Fig. 17.1 a), mod-
found in 50 – 70% of cases and the NOTCH sig- erate splenomegaly, hepatomegaly and meningeal