Leukemias
Acute leukemia
It is defined pathologically as blast cells leukemia or
malignancy of immature hemopoeitic cells.
Bone marrow shows more than 30% blast cells.
They are classified into two types; acute myeloblastic
leukemia (AML) and acute lymphoblastic leukemia
(ALL).
The different types of blast cells are recognized by:
1.
Morphology.
2.
Cytochemical stain.
3.
Immunological markers (MC antibodies).
4.
Cytogenetic.
5.
Molecular biology techniques.
6.
Rarely electron microscopy.
** In childhood leukemia (age less than 15 years), ALL
constitutes 80% of them; while in adulthood leukemia
(age more than 15 years), AML constitutes 80% of them.
Causes of acute leukemia:
Mostly unknown; but a number of environmental
agents have been implicated as inducers of certain
types of leukemia, e.g.:
1.
Ionizing radiation: Atomic bomb explosion in
Hiroshima.
2.
Chemical carcinogens: Benzene in shoes factory
and alkylating agents used to treat other
malignancies.
3.
Genetic disorders: Down syndrome and Fanconi's
syndrome.
4.
Acquired disorders: Myelodysplastic syndrome,
aplastic anemia, chemotherapy and radiotherapy.
5.
Chromosomal and oncogen abnormalities.
F.A.B. (French. American. British) classification:
It is an international classification of acute leukemias
according to morphology and cytochemistry.
ALL is classified into:
L1: small blast cells.
L2: intermediate size blast cells.
L3: Large size blasts with cytoplasmic vaculations
(Burkitt's cells).
AML is classified into:
M0: undifferentiated myeloblasts (need cell marker).
M1: Differentiated myeloblasts without maturation.
M2: Differentiated myeloblasts with maturation.
M3: Hypergranular promyelocytic.
M3-variant:
Micro-
or
hypo-granular
bi-lobed
promyelocytic.
M4: Myelo-monocytic with both granulocytic and
monocytic differentiation.
M5: M5a (Monoblastic) and M5b (Promonocytic
monocytic.
M6: Erythroblastic (erythroblasts more than 50% while
blasts either more or less than 30%).
M7: Megakaryoblastic (need cell marker).
** There is another less popular but more precise
classification called M.I.C. (morphology. Immunology.
Cytogenetic).
Clinical features:
1.
Features of bone marrow failure due to infiltration
by leukemia cells (blasts):
Anemia.
Infection (leucopenia).
Bleeding tendency (thrombocytopenia or DIC
as in M3).
2.
Fever.
3.
Bone & joint pain (more in ALL).
4.
Hepatosplenomegally (more in ALL).
5.
Lymphadenopathy (more in ALL, M4 and M5).
6.
Mediastinal masses (as in T cell-ALL).
7.
Extra-medullary disease: skin lesions and gum
swelling (as in M4 and M5).
8.
Chloroma (granulocytic sarcoma: a localized tumor
of blast cells).
9.
Hyperleukocytic syndrome: In 5% of AML patients,
the WBC count exceeds 100 ×10
9
/L and this leads
to leukostasis and endothelial damage (It affects
respiratory and central nervous systems).
Diagnosis
1.
History and physical examination.
2.
Peripheral blood film: Mostly anemia &
thrombocytopenia, in 50% leukocytosis and less
frequently leucopenia or normal WBC count. Blast
cells may be seen.
** Aleukemic leukemia: No blasts are seen in
peripheral blood.
3.
Bone marrow: Hypercellular marrow due to diffuse
blast cells infiltration with suppression of normal
hemopoeitic elements.
4.
Biochemical changes: Hyperuricemia (increased
serum uric acid from increased cell turnover),
hypercalcemia, hyperphosphatemia, hypo- or
hyperkalemia
and
hyponatremia
(due
to
antidiuretic hormone release).
Treatment
Combinations of chemotherapy.
Chronic lymphocytic leukemia (CLL)
It is a malignant proliferation of mature lymphocytes.
CLL can be distinguished from ALL by:
Cell morphology and degree of maturation: In ALL
cells are blasts which are immunologically
immature.
CLL affects mainly adults (older than 30 years);
whereas ALL affects mainly children and young
adults.
Clinical features
1.
Asymptomatic in 30% diagnosed during routine
blood examinations.
2.
Symmetrical painless lymphadenopathy: Cervical,
axillary and inguinal.
3.
Anemia.
4.
non specific systemic features, e.g. fever, sweating
or weight loss.
5.
Infection, e.g. severe chest infection (pneumonia).
6.
Splenomegally in about 50% of cases and
hepatomegally is less frequent.
Investigations
1.
Peripheral blood film: persistent lymphocytosis 5-
10 ×10
9
/L, prolymphocytes less than 10% and
smear cells (smudge cells) correlating with degree
of leukocytosis.
2.
Anemia & thrombocytopenia: Both are important in
prognosis and staging.
3.
Bone marrow: At least 40% lymphocytic infiltration,
also see pattern of infiltration whether diffuse, focal
or interstitial.
4.
Others: Hyperuricemia, auto-immune hemolytic
anemia and hypogammaglobulinemia.
Chronic myeloid leukemia (CML)
It is a clonal disease resulted from an acquired
genetic change in hemopoeitic stem cells.
This change alters stem cells proliferation and
generates population of differentiated cells
that gradually replace normal hemopoeitic
tissue and lead to greatly expanded total
myeloid mass.
At time of diagnosis; majority of patients have
Splenomegally, leukocytosis and Philadelphia
chromosome which is a translocation
chromosome (9:22) found in 92% of patients.
Median age of onset is 40-50 years.
The incidence is slightly higher in males than
females.
CML characterizes by three phases; chronic,
accelerated and blastic phases. Their criteria
are:
1.
Chronic phase: blast cells are less than 12% in
blood & bone marrow.
2.
Accelerated phase:
Increasing spleen size.
Increasing
leukocytes
count
despite
treatment.
Short leukocytes doubling time.
Blast cells more than 5% , but still less than
30% in bone marrow.
Anemia (Hb less than 10g/dl).
Thrombocytosis (platelets more than 1000
×10
9
/L).
Specific new cytogenetic abnormalities.
Increased marrow fibrosis.
3. Blastic phase: blast cells more than 30% in blood
or bone marrow. Mostly progress to AML (70%) and
less frequently to ALL.