LEUKEMIA

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 LEUKEMIA

It is a malignant
disease of a blood
forming organs. The
common feature of
leukemia is an
unregulated
proliferation of white
blood cells (WBCs)
in the bone marrow.
BY HOW QUICKLY THE DISEASE DEVELOPS:-

Chronic:
Leukemia cells come from mature, abnormal
cells. The cells thrive for too long and
accumulate. The cells grow slowly.
Acute:
Leukemia develops from early cells, called
"blasts". Blasts are young cells that divide
frequently. They target immature cells,
causing symptoms to appear quickly.
BY THE TYPE OF BLOOD CELL THAT IS AFFECTED:

Lymphoid cells:
Leukemia begins from white blood cells called
Lymphocytes.

Myeloid cells:
Leukemia involves the other 3 common types of white
blood cells known as granulocytes. They are neutrophils,
eosinophils, or basophils.
Blood Count

Blood Smear

Acute
Immunophenotyping – Flow Cytometry
Cytogenetic Analysis and Moleculer Subtype

Lymphoblastic
Leukemia
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 Heterogeneous hematologic disease characterized by the
proliferation of immature lymphoid cells in the bone
marrow, peripheral blood, and other organs.
 1.38 per 100.000 individual per year in US, 6.150 new cases
and 1.520 death estimated in 2020.
 Median age 15 years. 55.4% dx at younger than 20 yo. 28%
dx at 45 yo or older. 12.3% dx at 65 yo or older.
 ALL 75-80% acute leukemia among children, only 20% of
all leukemias among adults.
 Risk factor : older age (>70 y), exposure to chemotherapy
or radioation therapy, genetic disorders (down syndrome).
Rare (neurofibromatosis, klinefelter syndrome, fanconi
anemia, shwachman-Diamond syndrome, Bloom syndrome,
ataxia telangiectasia)
Diagnosis
 Clinical presentation non spesific, may include fatigure or lethargy,
constitutional symptoms (fevers, night sweats, weight loss), dyspnea,
dizziness, infections, easy brusing or bleeding.
 Hiperleukositosis + Bisitopenia (Anemia and Thrombocytopenia)
 Lymphadenopathy, hepatosplenomegaly, found in 20% of patients.
 Mediastium mass (T-ALL)
 Leukemic CNS : headache, vomit, neurological deficit
 Dx : 20% or >more bone marrow lymphoblast on hematopathology
review of BMA.
 When the disease is restricted to a mass lesion primarily involving nodal or
extranodal sites with no or minimal involvement in blood or bone marrow
(<20% lymphoblast in the marrow)  dx lymphoblastic lymphoma.
 Identification of spesific recurrent genetic abnormalities is critical for
disease evaluation, optimal risk stratification, and treatment planning.
Immunophenotyping
3 groups based on immunophenotype
 Precursor B-ALL
 Mature B-ALL
 Cell T-ALL

B cell lineage :
 Early precursor B-cell (presence of terminal deoxynucleotidyl transferase (TdT), CD19/CD22/CD79a, absence of CD10)
 Pre-B-cell (presence of cytoplasmic Ig, CD10/CD19/CD22/CD79a)
 Mature B-ALL (surface Ig, clonal lambda or kappa light chain, negative for TdT)

T cell lineage :
 Presence of CD3 or cell surface CD3, CD1a/CD2/CD5/CD7, TdT.
 CD52, expressed in 30%-50% cases in adults
 3 subgroup (cortical/thymic 56%, medullary/mature 21%, early 23%)
Cytogenetic and Molecular Subtypes
Overview of treatment phases in ALL
management

 Complex and intensive program in cancer therapy

 Differentbetween AYA and adults, and among subtypes of ALL,
but the basic treatment are similar.
 Treatment phase  induction, consolidation, maintanance.
 All tx regimens for ALL include CNS prophylaxis and/or treatment
 The most common use treatment :
 CALGB and Hyper CVAD
1. Induction Phase
 To reduce tumor burden by clearing as many leukemic cells as
possible from the bone marrow.
 Typically based on a backbone that includes a combination of
vincristine, anthracyclines (daunorobicin, doxorubicin) and
corticosteroid with or without L-asparaginase and/or
cyclophosphamide.
 Recommended by BFM/COF  combination of vincristine, an
anthracycline, a corticosteroid, and L-asparaginase.
 CALBG  5 drug regimen, 4 drug above + cyclophosphamide.
 Hyper-CVAD  eight alternating tx cycles with A regimen or B regimen
 A regimen : hyperfractioned cyclophosphamide, vincristine, doxorubicin,
dexamethasone

CNS Prophylaxis and Treatment

 To prevent CNS disease or relapse by clearing leukemic cells within

sites that cannot be readily acessed with systemic chemotherapy
because of the blood-brain barrier.
 Include : cranial irradiation, intratechal chemo (methotrexate,
cytarabine, corticosteroids) and/or systemic chemotherapy (high
dose methotrexate, intermediate/high dose cytarabine, L-
asparaginase)
 Typically given to all patients throughout the entire course of ALL
therapy, form induction, to consolidation, to the maintenance
phases of treatment
2. Consolidation Phase
 To eliminate any leukemic cells potentially remaining after induction therapy,
further eradicating residual disease.
 The postremission induction phase of tx (but before longterm maintenance tx) 
intensification therapy.
 Very largely among studies and patient populations for the combination of drugs
and duration of therapy
 High dose methotrexate, cytarabine, 6-mercaptopurine (6-MP),
cyclophosphamide, vincristine, corticosteroids, and L-
asparaginase  frequently incorporated into consolidation / intensification
regimens.
3. Maintenance Phase
 To
prevent disease relapse after postremission induction and
consolidation therapy.
 Most regimens  daily 6-MP and weekly methotrexate
(typically with the addition of periodic vincristine and
corticosteroid) for 2-3 years.
Targeted Agents?
 Treatment of Ph-positive disorder with TKIs
 Anti-CD20 monoclonal antibody (rituximab) for expressing B-Cell
lineage ALL (for mature B-ALL)
 Purine nucleoside, analog nelarabine  for the tx of relapsed/
refractory T-cell lineage ALL or lymphobalstic lymphoma
 Acute Myeloid
Leukemia

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CLASSIFICATION
The current categorization of AML uses the World Health Organization (WHO)
classification
AML with certain genetic abnormalities
– AML with a translocation between chromosomes 8 and 21
– AML with a translocation or inversion in chromosome 16
– AML with a translocation between chromosomes 9 and 11
– APL (M3) with a translocation between chromosomes 15 and 17
– AML with a translocation between chromosomes 6 and 9
– AML with a translocation or inversion in chromosome 3
– AML (megakaryoblastic) with a translocation between chromosomes 1
and 22
• AML with myelodysplasia-related changes
• AML related to previous chemotherapy or radiation
• AML not otherwise specified
– AML with minimal differentiation (M0)
– AML without maturation (M1)
– AML with maturation (M2)
– Acute myelomonocytic leukemia (M4)
– Acute monocytic leukemia (M5)
– Acute erythroid leukemia (M6)
– Acute megakaryoblastic leukemia (M7)
– Acute basophilic leukemia
– Acute panmyelosis with fibrosis
• Myeloid sarcoma
• Myeloid proliferations related to Down syndrome
• Undifferentiated and biphenotypic acute leukemias
dr.shumaylaaslam@gmail.com
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