acute lymphoblastic leukemia approach and treatment
TRANSCRIPT
Acute lymphoblastic leukemia
Dr. Ahmed Mjali
Commonest form of malignancy in childhood
Represent 80% of pediatric leukemia
Only 20% of adult acute leukemia
Acute onset with short history of duration.
Increase incidence in:
Radiation exposure and toxic chemicals
Down syndrome
Obesity
ALL AML
CMLCLL
AGECHILDREN YOUNG M
iddle AgeElderly
Acute Leukemia results from
a Maturation Arrest Causing Sustained
SELF-RENEWALAT THE EXPENSE OF
DIFFERENTIATION
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
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
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
LAP , HSMSternal tenderness Mediastenal mass presented in
15% of adult ALLTesticular swellingRetinal involvementCNS and meningeal involvement
5%
DIFFERENTIAL DIAGNOSIS Leukemic phase of Non Hodgkin's
Lymphoma Reactive lymphocytosis due to
infections (EBV ,pertussis) Metastatic tumors in bone marrow ITPAML
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
How does ALL classified?
FAB
WHO
IMMUNOPHENOTYPIC
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
FAB 1
Lymphoblasts: Small & Monomorphic
FAB 2
Lymphoblasts: Large & Heterogeneous
FAB 3
Large varied cells with vacuoles
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
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%
Treatment of ALL
Remission induction4-6 weeks
Intensification6 months
Maintenance therapy
2 years
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
Q: which of the following targeted agents have been shown to be beneficial in adult ALL?
A. Imatinib B. Alemtuzumab C. Gemtuzumab D. Sunitinib
Questions?????Does my patients cure?
There is possibility of relapse?
Does my patient need bone marrow transplant? And at which time?
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
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
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
SurvivalChildren • CR 97%• At 5 years DFS >75%
Adult• CR 75-90%• 5 –years DFS 25-50%
Thank you