Acute Leukemia: Thirunavukkarasu Murugappan

ACUTE LEUKEMIA
Thirunavukkarasu murugappan
INTRODUCTION:
• Leukemia is a group of malignant disorder, affecting the blood and blood –
forming tissue of the bone marrow lymph system and spleen.
 It is a broad term covering a spectrum of diseases which includes Acute
lymphoblastic leukemia (ALL), Acute Myelogenous Leukaemia (AML),
Chronic lymphocytic Leukaemia (CLL), Chronic Myelogenous
Leukaemia(CML)
• Leukaemia is the most common
childhood malignancy
EPIDEMIOLOGY :
• It accounts for 30% of all cancers diagnosed in children under 15 years of age in
industrialized countries.
• Around 2000, the average incidence for this age group in the European Region
was 46.7 cases per million per year, with a slightly lower level in eastern than in
western European countries.
• European population based cancer registries show an average increase in the
incidence of childhood leukaemia of 0.7% per year between 1970 and 1999.
Incidence in European nations of childhood
leukemia <15 yrs of age:
MORTALITY RATES OF LEUKEMIA (1950-
1995)
HEMOPOIESIS: naïve
B-lymphocytes
Plasma
Lymphoid cells
progenitor T-lymphocytes
Hematopoietic Myeloid Neutrophils

stem cell progenitor
Eosinophils
Basophils
Monocytes
Platelets
Red cells
ACUTE LYMPHOBLASTIC LEUKEMIA:
• Acute lymphoblastic leukemia (ALL) is the most common form among childhood
leukemias representing 77% of all the reported cases
• The peak incidence of ALL is 2-5 yrs and occurs in children less than 14yrs and
adults more than 65 yrs
• Males are more affected compared to females
• Factors predisposing to this disease are:
• Chromosomal abnormalities including Down syndrome, Bloom syndrome,
turner syndrome, and Fanconi syndrome.
• Environmental factors like exposure to ionizing radiation and electromagnetic
fields, parental use of alcohol and tobacco
• Children with various congenital immunodeficiencies (ie, Wiskott
-Aldrich syndrome, congenital hypogammaglobulinemia, ataxia-telangiectasia
etc )
PATHOGENESIS:
• cancer is caused by damage to DNA that leads to uncontrolled cellular growth
and spread throughout the body, either by increasing chemical signals that cause
growth, or interrupting chemical signals that control growth. Damage can be
caused through the formation of fusion genes, as well as the dysregulation of a
proto-oncogene via juxtaposition of it to the promotor of another gene, e.g. the
T-cell receptor gene. This damage may be caused by environmental factors such
as chemicals, drugs or radiation.
• It arising from a single lymphoid stem cell, with impaired maturation and
accumulation of the malignant cells in the bone marrow.
TYPES:
B-CELL LINEAGE
Abt 75% of ALL is pre B cell

type. Abt 80% of these have cALL
antigen positive.
LEUKEMIA
T-CELL LINEAGE
15% are represented by

PreT cell leukemia
SIGNS AND SYMPTOMS:
• Initial symptoms is usually nonspecific.
• Followed by anorexia, pallor, weight loss and low grade fever
• Bone pain is generally present involving the lower
extremities and can be very severe waking the patient in the
night
• Abdomen and joint pain can also occur
• pallor, listlessness, purpuric and petechial skin lesions, or
mucous membrane hemorrhage may reflect bone marrow
failure.
• Anemia, thrombocytopenia, generalized lymphadenopathy,
hepatosplenomegaly and upper respiratory tract infections.
Upper respiratory tract infections may preceed 1-2 months
before the classic presentation of illness.
• CNS involvement represented by high intracranial pressure.
DIAGNOSIS:
• Anemia, low Hb and hematocrit, thrombocytopenia and leukemic cells < 10,000
• Bone marrow biopsy will show immature lymphoblast >20% in the marrow.
• Negative myeloperoxidase and positive terminal deoxynucleotidyl transferase (TdT)
• Histologic classification:
• L1 – Small cells with homogeneous chromatin, regular nuclear shape, small or absent
nucleolus, and scanty cytoplasm; subtype represents 25-30% of adult cases.
• L2 – Large and heterogeneous cells, heterogeneous chromatin, irregular nuclear shape, and
nucleolus often large; subtype represents 70% of cases (most common)
• L3 – Large and homogeneous cells with multiple nucleoli, moderate deep blue cytoplasm,
and cytoplasmic vacuolization that often overlies the nucleus (most prominent feature);
subtype represents 1-2% of adult cases
• The WHO classifies the L1 and L2 subtypes of acute lymphoblastic leukemia (ALL) as
either precursor B lymphoblastic leukemia/lymphoblastic lymphoma or precursor T
lymphoblastic leukemia/lymphoblastic lymphoma depending on the cell of origin. The L3
subtype of ALL is included in the group of mature B-cell neoplasms, as the subtype Burkitt
lymphoma/leukemia.
• Other abnormalities:
• Elevated prothrobin time, decreased fibrinogen levels
• Schistocytes are sometimes seen if DIC is present.
• Most patients with acute lymphoblastic leukemia (ALL) have an elevated
lactic dehydrogenase level (LDH), and they frequently have an elevated uric
acid level.
• Liver function tests and blood urea nitrogen (BUN)/creatinine
determinations are necessary before the initiation of therapy.
• Lab cultures to exclude underlying infections
• Imaging studies
• Chest x-ray films may reveal signs of pneumonia and/or a prominent
mediastinal mass in some cases of T-cell acute lymphoblastic leukemia
(ALL).
• Computed tomography (CT) scans can further define the degree of
lymphadenopathy in some patients, including those with mediastinal masses.
• Multiple-gated acquisition (MUGA) scans or electrocardiographs
(ECGs) are needed when the diagnosis of acute lymphoblastic leukemia
(ALL) is confirmed, because many chemotherapeutic agents used in the
treatment of acute leukemia are cardiotoxic.
TREATMENT:
• combination chemotherapy
• first goal is complete remission
• further Rx to prevent relapse
• supportive medical care
• transfusions, antibiotics, nutrition
• psychosocial support
• patient and family
• Phases of ALL treatment
• induction
• intensification
• CNS prophylaxis Post remission therapy
• maintenance
PHASES OF TREATMENT:
• Induction therapy: 4 drug regimen or 5 drug regimen with vincristine,

prednisone, anthracycline, cyclophosphamide, and L -asparaginase over 4-
6weeks. Complete remission achieved in 68-75%
• consolidation therapy with daunorubicin and cytosine arabinoside
• Intensification of maintenance therapy from a 12-month course of a 4-drug
regimen compared with a 14-month course
• An important site of leukemic infiltration is the meninges; prophylaxis and
treatment may include high-dose intrathecal methotrexate, cytosine arabinoside,
and corticosteroids. Cranial nerve or whole-brain irradiation may be necessary
PROGNOSIS:
• Favorable prognostic factors are
• Age 3 to 7 yr
• WBC count < 25,000/μL
• French-American-British (FAB) L1 morphology
• Leukemic cell karyotype with > 50 chromosomes and t(12;21)
• No CNS disease at diagnosis
• Unfavorable factors are
• A leukemic cell karyotype with chromosomes that are normal in number but
abnormal in morphology (pseudodiploid)
• Presence of the Philadelphia(Ph) chromosome t(9;22)
• Increased age in adults
• B-cell immunophenotype with surface or cytoplasmic immunoglobulin
ACUTE MYELOID LEUKEMIA
• AML accounts for 11% of the cases of childhood leukemia in the USA.
• Acute myeloid leukemia (AML), also known as acute myelogenous leukemia,
is a cancer of the myeloid line of blood cells
Auer rods which
is pathognomic
for AML it is
absent in ALL
Type Name Genetics
M0 minimally differentiated acute myeloblastic leukemia
M1 acute myeloblastic leukemia, without maturation
acute myeloblastic leukemia, with granulocytic t(8;21)(q22;q2),
M2
maturation t(6;9)
M3 promyelocytic, or acute promyelocytic leukemia (APL) t(15;17)
inv(16)(p13q22),
M4 acute myelomonocytic leukemia
del(16q)
M4eo myelomonocytic together with bone marrow eosinophilia inv(16), t(16;16)
acute monoblastic leukemia (M5a) or acute monocytic del (11q), t(9;11),
M5
leukemia (M5b) t(11;19)
acute erythroid leukemias, including erythroleukemia
M6
(M6a) and very rare pure erythroid leukemia (M6b)
M7 acute megakaryoblastic leukemia t(1;22)
M8 acute basophilic leukemia
Clinical manifestation
Similar to ALL plus sternal tenderness.
• Patient may have hypertrophy and
swelling of the gums
• Choloroma a tumor outside the
bone marrow
Diagnosis
Low RBC, Hb, Hct, low platelet count, low to high WBC count with myeloblasts.
Routine cytogenetics and FISH
Technique (fluorescent insitu hybridization)
To find the mutations and translocation if the genes
A
Pathognomic feature:
Auer rods B
C
TREATMENT
• Intensive chemotherapy with cytrabines, anthracyclines,
doxorubicin
• The M3 subtype of AML, also known as acute
promyelocytic leukemia, is almost universally treated
with the drug ATRA (all-trans-retinoic acid) in addition
to induction chemotherapy. It is highly responsive and
makes bone marrow transplantation unnecessary in these
patients
• Stem cell transplatation is highly recommended in risk
patients of relapse like patients with Myeloproliferative
disease or Myelodysplastic syndrome, M0 type and M5
type
• Additional advantage of stem cell transplant is graft
versus leukemic effect
PROGNOSIS:
Risk Category Abnormality 5-year survival Relapse rate

t(8;21), t(15;17),
Good 70% 33%
inv(16)
Normal, +8, +21,

+22, del(7q),
del(9q), Abnormal
Intermediate 48% 50%
11q23, all other
structural or
numerical changes
-5, -7, del(5q),

Abnormal 3q,
Poor 15% 78%
Complex
cytogenetics
THANK YOU!!!!

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ACUTE LEUKEMIA

Hematopoietic Myeloid Neutrophils

Abt 75% of ALL is pre B cell

15% are represented by

• Induction therapy: 4 drug regimen or 5 drug regimen with vincristine,

• Favorable prognostic factors are

Risk Category Abnormality 5-year survival Relapse rate

Normal, +8, +21,

-5, -7, del(5q),

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