2. What are leukemias???
• Leukaemias are malignant disorders of the
haematopoietic stem cell compartment,
characteristically associated with increased
numbers of white cells in the bone marrow
and/or peripheral blood.
• The course of leukaemia may vary from a few
days or weeks to many years, depending on
the type.
3. Epidemiology
• ALL, comprises 80% of the acute leukemias of
childhood.
• Peak incidence is between 3 and 7 years of
age.
• Appr. 20% of adult acute leukemias is ALL.
• AML - median age at presentation of 60 years
4.
5. RISK FACTORS
• Environmental factors
– Radiation
– Benzene
– Alkylating agents,
topoisomerase II inhibitors,
and other cytotoxic drugs
– Tobacco smoke
• Acquired diseases
– Clonal myeloid diseases
– Chronic myelogenous
leukemia
– Primary myelofibrosis
– Essential thrombocythemia
– Polycythemia vera
– Myeloma
• Other disorders
– Human immunodeficiency virus
infection
– Thyroid disorders
– Polyendocrine disorders
• Inherited or Congenital
Conditions
6. Signs and Symptoms
GENERAL
• Due to anemia pallor, fatigue, weakness,
palpitations, and dyspnea on exertion.
• Weakness, loss of sense of well-being, and
fatigue on exertion can be disproportionate to
the severity of anemia.
• Easy bruising, petechiae, epistaxis, gingival
bleeding, conjunctival hemorrhages, and
prolonged bleeding from skin injuries reflect
thrombocytopenia.
7. • Pustules or other minor pyogenic infections of
the skin and of minor cuts or wounds are most
common.
• The most common pathogens are gram-
negative bacteria (Escherichia coli, Klebsiella,
Pseudomonas) or fungi (Candida, Aspergillus)
• Major infections, such as sinusitis, pneumonia,
pyelonephritis, and meningitis, are
uncommon at presentation
8. • Anorexia and weight loss are frequent
findings.
• Fever is present in many patients at the time
of diagnosis.
• Palpable splenomegaly or hepatomegaly
occurs in approximately one-third of patients.
• Lymphadenopathy is extremely uncommon
except in the monocytic variant of AML.
9. Systemic Involvement
• Skin involvement may be of three types:
– nonspecific lesions
– leukemia cutis
– granulocytic (myeloid) sarcoma of skin and subcutis
• Sensory organ involvement is very unusual, but
retinal, choroidal, iridial, and optic nerve
infiltration can occur
• Oral manifestations
– Gingival or periodontal infiltration
– Dental abscesses may lead to an extraction
– Prolonged bleeding of an infected tooth socket
10. • The respiratory tract can be involved by:
– Infiltrates or tumors leading to laryngeal obstruction
– Parenchymal infiltrates
– Alveolar septal infiltration
– Pleural seeding.
• Central or peripheral nervous system - meningeal
involvement is an important consideration in the
treatment of the monocytic type of AML.
• Osteoarticular symptoms
– Bone pain
– Joint pain
– Bone necrosis
– Crystal-induced arthritis
• Calcium pyrophosphate dihydrate (pseudogout)
• Monosodium urate (gout)
11. LABORATORY FEATURES
BLOOD PICTURE:
• The hallmark of acute leukemia is the combination of
pancytopenia with circulating blasts.
• Anemia is a constant feature - inadequate production
of red cells
• Thrombocytopenia is nearly always present -
inadequate production and decreased survival of
platelets.
• The TLC is < 5000/ L (5 x 109 /L) & absolute neutrophil
count is < 1000/ L (1 x 109 /L) in approximately half of
patients at the time of diagnosis.
12. Blood film of AML without maturation (acute myeloblastic leukemia). Five
myeloblasts are evident. High nuclear-to-cytoplasmic ratio. Agranular
cells.
13. ALL with large blasts showing prominent nucleoli, moderate
amounts of cytoplasm, and an admixture of smaller blasts
14. Typical lymphoblasts with scanty cytoplasm, regular nuclear
shape, fine chromatin, and indistinct nucleoli
15. Bone Marrow Findings
• The marrow always contains leukemic blast
cells
• The bone marrow is usually hypercellular and
dominated by blasts.
• More than 20% marrow blasts are required to
make a diagnosis of acute leukemia.
16. • Hyperuricemia
• If DIC is present
– the fibrinogen level will be reduced
– the prothrombin time prolonged
– fibrin degradation products or fibrin D-dimers
present.
• Patients with ALL (especially T cell) may have a
mediastinal mass visible on chest radiograph.
• Meningeal leukemia will have blasts present in
the spinal fluid, seen in approximately 5% of
cases in monocytic types of AML and can be
seen with ALL.
17.
18. • The phenotype of leukemia cells is usually
demonstrated by flow cytometry or
immunohistochemistry.
• AML cells usually express myeloid antigens such
as CD 13 or CD 33 and myeloperoxidase.
• ALL cells of B lineage will express CD19, common
to all B cells, and most cases will express CD10,
formerly known as the “common ALL antigen.”
• ALL cells of T lineage will usually not express
mature T-cell markers, such as CD 3, 4, or 8, but
will express some combination of CD 2, 5, and 7
and do not express surface immunoglobulin.
• Almost all ALL cells express terminal
deoxynucleotidyl transferase (TdT).
19.
20. Management
Supportive therapy
• Anaemia - red cell concentrate transfusions.
• Bleeding
– Thrombocytopenic bleeding requires platelet
transfusions, unless the bleeding is trivial.
– Prophylactic platelet transfusion should be given to
maintain the platelet count above 10 × 109/L.
Coagulation abnormalities
• Infection
– Fever (> 38°C) lasting over 1 hour in a neutropenic
patient indicates possible septicaemia
21. • Empirical therapy - combination of an
aminoglycoside (e.g. gentamicin) and a broad-
spectrum penicillin (e.g. piperacillin/tazobactam)
or a single-agent beta-lactam (e.g. meropenem)
• The organisms most commonly associated with
severe neutropenic sepsis are:
– Gram-positive bacteria
• Staphylococcus aureus
• Staph. epidermidis,
– Gram-negative bacteria
• Escherichia coli
• Pseudomonas
• Klebsiella spp.
22. • Gram-positive infection may require
vancomycin therapy.
• If fever has not resolved after 3–5 days,
empirical antifungal therapy (e.g. a liposomal
amphotericin B preparation, voriconazole or
caspofungin) is added.
• Oral and pharyngeal candida infection –
fluconazole, itraconazole
• Reactivation of herpes simplex infection
• Herpes zoster
– Chickenpox
– Shingles
23. • Metabolic problems
– Frequent monitoring of fluid balance and renal,
hepatic and haemostatic function is necessary.
– Renal toxicity occurs with some antibiotics (e.g.
aminoglycosides) and antifungal agents
(amphotericin).
– Cellular breakdown during induction therapy (tumour
lysis syndrome)
• Hyperkalaemia
• Hyperuricaemia,
• Hyperphosphataemia
• Hypocalcaemia.
– Allopurinol and intravenous hydration are given to try
to prevent this
24. Specific Treatment
• Remission induction
– In this phase, the bulk of the tumour is destroyed by
combination chemotherapy.
– The patient goes through a period of severe bone marrow
hypoplasia
• Remission consolidation
– If remission has been achieved, residual disease is attacked by
therapy during the consolidation phase.
– This consists of a number of courses of chemotherapy, again
resulting in periods of marrow hypoplasia.
• Remission maintenance
– If the patient is still in remission after the consolidation phase
for ALL, a period of maintenance therapy is given, with the
individual as an outpatient and treatment consisting of a
repeating cycle of drug administration.
25.
26. Haematopoietic Stem Cell
Transplantation
• Transplantation of haematopoietic stem cells
(HSCT) has offered the only hope of ‘cure’ in a
variety of haematological and non-
haematological disorders
• The type of HSCT is defined according to the
donor and source of stem cells into:
– Allogenic HSCT
– Autologus HSCT
27. • In allogeneic HSCT, the stem cells come from a
donor either related (usually an HLA-identical
sibling) or a closely HLA-matched volunteer
unrelated donor (VUD).
• In an autologous transplant, the stem cells are
harvested from the patient and stored in the
vapour phase of liquid nitrogen until required.
