acute lymphoblastic leukemia approach and treatment

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