Acute leukemia is a malignant clonal disorder characterized by the accumulation of immature blast cells in the bone marrow, which replaces normal marrow tissue and results in bone marrow failure and peripheral blood cytopenias. There are two main types: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). ALL involves abnormal proliferation of immature lymphocytes while AML involves the myeloid cell lineages. Diagnosis involves physical exam, blood tests, bone marrow aspiration and biopsy. Treatment for both types usually involves intensive multi-agent chemotherapy, while AML may also involve all-trans retinoic acid. Prognosis depends on various risk factors like age, white blood cell count, and cytogenetics.

1. ACUTE
LEUKEMIA

2. What is leukemia?
• Leukemia is a type of cancer that occurs in
blood forming tissues, such as the bone
marrow and the lymphatic system.
• It is characterized by an abnormal increase
of white blood cells.

3. Signs & Symptoms
• Leukemia symptoms vary on the type of
leukemia, but a few common symptoms
include:
– Fever or chills
– Persistent fatigue or weakness
– Bone pain or tenderness
– Excessive sweating
– Frequent infections

4. Four Types of Leukemia:
Leukemia
Chronic
Chronic
Lymphocytic
Leukemia
(CLL)
Chronic
Myeloid
Leukemia
(CML)
Acute
Acute
Lymphocytic
Leukemia (ALL)
Acute Myeloid
Leukemia (AML)

5. Acute leukaemia is a clonal ( derived from a
single cell) malignant disorder characterised
by the accumulation of immature blast cells in
the BM, which replace normal marrow tissue,
including haemopoietic precursor cells.
This results in BM failure, reflected by peripheral
blood cytopenias and circulating blast cells.
Infiltration of various organs is also a
feature of some forms of leukaemia

6. (a) acute lymphoblastic leukemia (ALL), in which the
abnormal proliferation is in the immature
lymphocytes
(b) acute myeloid leukemia (AML), which involves the
myeloid lineages ( cells from which neutrophils,
eosinophils, monocytes, basophils, megakaryocytes,
etc. are derived).
• The distinction between the two leukemias is
based on morphological, cytochemical,
immunological and cytogenetic differences and is of
paramount importance as the treatment and
prognosis are usually different

7. Subclassification
• It is further subdivided on the basis of
morphological criteria:
• ALL into FAB
(French-American-British) subtypes L1, L2, and
L3, and
• AML into FAB subtypes M0 to M7

8. FAB for AML
M0 AML with minimal differentiation
M1 AML without maturation
M2 AML with maturation
M3 Acute promyelocytic leukaemia
M4 Acute myelomonocytic leukaemia
M5 Acute monocytic/monoblastic leukaemia
M6 Acute erythroleukaemia
M7 Acute megakaryoblastic leukaemia

9. FAB Classification of ALL
L1: Small homogeneous blasts; mostly in
children
L2: Large heterogeneous blasts; mostly in
adults
L3: “Burkitt” large basophilic B-cell blasts with
vacuoles

10. Incidence for ALL
ALL is most common in the age 2-10 years, (
peak at 3-4).
Secondary rise after 40 years.
In children it is the most common malignant
disease and accounts for 85% of childhood
leukaemia

11. Incidence for AML
AML accounts for 10-15% of childhood
leukemia, but it is the commonest leukaemia
of adulthood. The incidence increases with
age, and the median age at presentation is 60
years.

12. Acute myelogenous leukemia
• (AML) is a clonal hematopoietic disorder resulting from
genetic alterations in normal hematopoietic stem cells.
• These changes alter normal hematopoietic growth and
differentiation, resulting in an accumulation of large
numbers of abnormal, immature myeloid cells in the
bone marrow and peripheral blood.
• These cells are capable of dividing and proliferating,
but cannot differentiate into mature hematopoietic
cells.
• AML is more common in men than women.
• AML is the most common acute leukemia affecting
adults, and its incidence increases with age.

13. Pathogenesis
• The malignant cell in AML is the myeloblast.
• In normal hematopoiesis, the myeloblast is an
immature precursor of myeloid white blood
cells; a normal myeloblast will gradually
mature into a mature white blood cell.
• In AML, though, a single myeloblast
accumulates genetic changes which "freeze"
the cell in its immature state and
prevent differentiation.

16. Chromosomal translocation
The translocation fuses the AML1 gene (also
called RUNX1) on chromosome 21 with the ETO
gene (also referred to as the RUNX1T1 gene that
encodes the CBFA2T1 protein) on chromosome 8.
 CBFA2T1 protein - This protein has multiple
effects on the regulation of the proliferation, the
differentiation, and the viability of leukemic cells.

17. •
P. Smear AML
• The numerous myelocytes have abundant cytoplasm
with prominent specific granulation

18. •
Auer Rods in Leukemia cells

19. Presentation FOR AML
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Epistaxis
Bleeding gums
Bruising/contusions
Bone pain or tenderness
Fatigue
Fever
Heavy menstrual periods
Pallor
Shortness of breath (gets worse with exercise)
Skin rash or lesion
Swollen gums (rare)
Weight loss

20. Patients with Aml

21. Blood film of patient with ALL
large homogenous lymphoblasts,
prominent nucleoli,round nuclei

22. Presentation for ALL
Organ infiltration: in ALL is bone pain, superficial
lymphadenopathy, abdominal distension due to
abdominal lymphadenopathy and
hepatosplenomegaly, respiratory embarrassment
due to a large mediastinal mass, testicular
enlargement, or a meningeal syndrome.
Gum hypertrophy and skin infiltration are more
commonly seen in AML than in ALL

23. DIAGNOSIS
• Physical exam
• CBC(Complete Blood Count) usually but not invariably shows reduced Hb conc.
and platelet count. The WBC can vary from 1000 to
200000, and the differential WBC is often abnormal,
with neutropenia and the presence of blast cells.
The anaemia is a normochromic, normocytic
anaemia, and the thrombocytopenia may be severe

24. • Bone marrow aspiration: with or without
trephine bx is essential to confirm acute
leukaemia. The marrow is usually
hypercellular, with a predominance of
immature (blast) cells

25. Jamshidi trephine & Salah aspiration
needle
used for bone marrow aspiration

27. Biochemical screening
• when the leucocyte count is very high, there
may be evidence of renal impairment and
hyperuricaemia

28. TREATMENT
• Immediate (same day) referral to specialist
• Prompt diagnosis
• Intensive supportive care
• Systemic chemotherapy
• Treatment directed at CNS (in children and in
adult ALL)
• Minimising early and late toxicity of treatment

29. • Prophylactic PLT transfusions are given if PLT
count is 10000.
• Clotting abnormalities may result from a DIC
where infusions of FFP and cryoprecipitate
may be beneficial.
• Packed red cell transfusions are given for
symptomatic anaemia, though these are
contraindicated if the WBC is extremely high.
In most patients a central venous catheter is
inserted to facilitate blood product support,
administration of chemotherapy and
antibiotics, and frequent blood sampling

30. Chemotherapy
In AML:
• treated with 4 or 5 courses of intensive
chemotherapy when there is intent to cure. Each
course consists of 10 days of chemotherapy.
Subsequent courses are started after cell counts
have recovered and response to treatment is
established. In AML M3 the drug ATRA (all-transretinoic acid) is used as an adjunct to
chemotherapy as it causes differentiation of the
malignant clone.

31. • In ALL the induction course is followed by two
or more consolidation periods and by
treatment directed at the CNS, followed by
long term maintenance or continuation
treatment for up to two years. This has been
shown to improve long term cure rates in ALL,
though not in AML

32. Distinguishing AML from ALL
– AML: Auer rods, cytoplasmic granules
– ALL: no Auer rods or granules.

33. Prognosis
• Poor prognosis in ALL
Age
< 1 year or > 10 years
Sex
Male
Presenting WBC
50000
CNS disease
at presentation
Presence of blasts in CSF
Remission problems Failure to remit after first induction
treatment
Cytogenetics
Philadelphia positive—that is,
t(9;22)or t(4;11) ALL

34. Poor prognosis in AML
• Age
• Sex
> 60 years
Male or female
Presenting WBC
>50000
CNS disease
at presentation
Remission problems
Presence of blasts in CSF
20% blasts in BM after 1st course
Cytogenetics
Deletions or monosomy of
chromosome 5 or 7 or complex chromosomal
abnormalities

35. Survival
Type
Childhood ALL
Adult ALL
AML, aged < 60 yr
AML, aged > 60 yr
At 5 years
65-75%
20-45%
35-40%
10%