Acute lymphoblastic leukemia approach and treatment
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Transcript of Acute lymphoblastic leukemia approach and treatment
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Acute lymphoblastic leukemia
Dr. Ahmed Mjali
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Commonest form of malignancy in childhood
Represent 80% of pediatric leukemia
Only 20% of adult acute leukemia
Acute onset with short history of duration.
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Increase incidence in:
Radiation exposure and toxic chemicals
Down syndrome
Obesity
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ALL AML
CMLCLL
AGECHILDREN YOUNG M
iddle AgeElderly
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Acute Leukemia results from
a Maturation Arrest Causing Sustained
SELF-RENEWALAT THE EXPENSE OF
DIFFERENTIATION
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HEMOPOIESISMYELOID/ LYMPHOID
STEM CELLS(CD34)
LYMPHOID STEM CELLS
Pre-T
Thymocyte
Peripheral T Cells
T-Helper
T-Supp.
Pro-B
Pre-B
B- Mature
LPCPLASMACELL
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HEMOPOIESISMYELOID/ LYMPHOID
STEM CELLS(CD34)
LYMPHOID STEM CELLS
Pre-T
Thymocyte
Peripheral T Cells
T-Helper
T-Supp.
Pro-B
Pre-B
B- Mature
LPC
PLASMACELL
ALL
CLL
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What are common presentation in ALL? Ineffective hematopoiesis due to the
excessive proliferation of lymphoid precursor cells in bone marrow:
Neutropenia – fever, chillsThrombocytopenia – bleeding,
bruising Anemia – weakness, fatigue
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LAP , HSMSternal tenderness Mediastenal mass presented in
15% of adult ALLTesticular swellingRetinal involvementCNS and meningeal involvement
5%
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DIFFERENTIAL DIAGNOSIS Leukemic phase of Non Hodgkin's
Lymphoma Reactive lymphocytosis due to
infections (EBV ,pertussis) Metastatic tumors in bone marrow ITPAML
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Diagnostic work upHistory & examination Peripheral Blood smear and peripheral
blood cytometry Bone marrow aspiration & biopsy PT , PTT , D- dimer fibrinogen LDH , uric acid , electrolyte CT / MRI of head if neurologic symptoms CT chest (T-ALL) Echocardiogram to assess cardiac
function
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How does ALL classified?
FAB
WHO
IMMUNOPHENOTYPIC
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FAB classification (morphological)
ALL L1 ALL L2 ALL L3 (Burkitts type) In childhood – L1 is the most
common type In adults – L2 is the most
common type
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FAB 1
Lymphoblasts: Small & Monomorphic
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FAB 2
Lymphoblasts: Large & Heterogeneous
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FAB 3
Large varied cells with vacuoles
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WHO classification of ALL (2008)1-B lymphoblastic leukemia/lymphoma nos 2- B lymphoblastic leukemia/lymphoma
with recurrent abnormalities t( 9; 22) , BCR ABL1 t( v; 11q23) MLL rearrangement t (12;21) ETV6-RUNX1 With hypodiploidy With hyperdiploidy t (5;14) il3 –igh t ( 1;19) E2A-PBX1 (tcf3-pbx1) 3-T lymphoblastic leukemia/lymphoma
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Immunophenotyping (flow cytometry)According to the lymphoid cell involved: B-cell ALL (85%)• Early pre-B ALL (pro-B ALL) - 10% • common ALL - 50% • pre-B ALL - 10%• mature B-cell ALL (Burkitt leukemia) - 4% T-cell ALL (15%) • pre-T ALL - 5% to 10% • mature T-cell ALL - 15% to 20%
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Treatment of ALL
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Remission induction4-6 weeks
Intensification6 months
Maintenance therapy
2 years
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Q:Why we give CNS prophylaxis?Because CNS is a sanctuary area for
leukemia cells and without chemotherapy the risk of relapse is about 30%.
Q: Dexamethasone has replaced prednisone in ALL induction therapy because improve penetration to:
A. TestesB. SpleenC. Bone marrowD. Brain
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Q: which of the following targeted agents have been shown to be beneficial in adult ALL?
A. Imatinib B. Alemtuzumab C. Gemtuzumab D. Sunitinib
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Questions?????Does my patients cure?
There is possibility of relapse?
Does my patient need bone marrow transplant? And at which time?
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What Minimal Residual Disease MRD means?
Its assess response to chemotherapy
Can identify VERY LOW number of leukemic cells (1:10000)
It can be done either by flow cytometry or RT-PCR analysis
It’s the most important predictor factor of relapse
Its done after completion of initial treatment
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Timing of bone marrow transplantPrimary induction failure and relapse
Presence of MRD after initial treatment
After second complete remission
High resolution HLA donor is recommended at diagnosis for all patients
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Prognosis favorable unfavorable
≤ 35 y >35 y Age
≤ 30 ,000 /mm >30,000 /mm White blood cell
other B-cell precursor Immunophenotype
other t(9;22)t(4;11)t(1;19)
Cytogenetics
<4 weeks > 4 weeks Time to complete response
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SurvivalChildren • CR 97%• At 5 years DFS >75%
Adult• CR 75-90%• 5 –years DFS 25-50%
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Thank you