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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.
 Increase incidence in:
Radiation exposure and toxic
chemicals
Down syndrome
Obesity
ALL AML
CMLCLL
AGE
YOUNG
Elderly
Acute Leukemia
results from
a Maturation Arrest
Causing Sustained
SELF-RENEWAL
AT THE EXPENSE OF
DIFFERENTIATION
HEMOPOIESIS
MYELOID/ LYMPHOID
STEM CELLS
(CD34)
LYMPHOID
STEM CELLS
Pre-T
Thymocyte
Peripheral T
Cells
T-
Helper
T-
Supp.
Pro-B
Pre-B
B- Mature
LPC
PLASMA
CELL
HEMOPOIESIS
MYELOID/ LYMPHOID
STEM CELLS
(CD34)
LYMPHOID
STEM CELLS
Pre-T
Thymocyte
Peripheral T Cells
T-
Helper
T-
Supp.
Pro-B
Pre-B
B- Mature
LPC
PLASMA
CELL
ALL
CLL
What are common presentation in
ALL?
Ineffective hematopoiesis due to the
excessive proliferation of lymphoid
precursor cells in bone marrow:
 Neutropenia – fever, chills
Thrombocytopenia – bleeding, bruising
Anemia – weakness, fatigue
 LAP , HSM
 Sternal tenderness
 Mediastenal mass presented in 15%
of adult ALL
 Testicular swelling
 Retinal involvement
 CNS 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
 ITP
 AML
Diagnostic work up
 History & 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
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 induction
4-6 weeks
Intensification
6 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. Testes
B. Spleen
C. Bone marrow
D. 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
transplant
 Primary 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
favorableunfavorable
≤ 35 y>35 yAge
≤ 30 ,000 /mm>30,000 /mmWhite blood cell
otherB-cell precursorImmunophenotype
othert(9;22)
t(4;11)
t(1;19)
Cytogenetics
< 4 weeks> 4 weeksTime to complete
response
Survival
Children
• CR 97%
• At 5 years DFS >75%
Adult
• CR 75-90%
• 5 –years DFS 25-50%
Acute lymphoblastic leukemia approach and treatment

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Acute lymphoblastic leukemia approach and treatment

  • 1.
  • 2.  Commonest form of malignancy in childhood  Represent 80% of pediatric leukemia  Only 20% of adult acute leukemia  Acute onset with short history of duration.
  • 3.  Increase incidence in: Radiation exposure and toxic chemicals Down syndrome Obesity
  • 5. Acute Leukemia results from a Maturation Arrest Causing Sustained SELF-RENEWAL AT THE EXPENSE OF DIFFERENTIATION
  • 6. HEMOPOIESIS MYELOID/ LYMPHOID STEM CELLS (CD34) LYMPHOID STEM CELLS Pre-T Thymocyte Peripheral T Cells T- Helper T- Supp. Pro-B Pre-B B- Mature LPC PLASMA CELL
  • 7. HEMOPOIESIS MYELOID/ LYMPHOID STEM CELLS (CD34) LYMPHOID STEM CELLS Pre-T Thymocyte Peripheral T Cells T- Helper T- Supp. Pro-B Pre-B B- Mature LPC PLASMA CELL ALL CLL
  • 8. What are common presentation in ALL? Ineffective hematopoiesis due to the excessive proliferation of lymphoid precursor cells in bone marrow:  Neutropenia – fever, chills Thrombocytopenia – bleeding, bruising Anemia – weakness, fatigue
  • 9.  LAP , HSM  Sternal tenderness  Mediastenal mass presented in 15% of adult ALL  Testicular swelling  Retinal involvement  CNS and meningeal involvement 5%
  • 10.
  • 11. DIFFERENTIAL DIAGNOSIS  Leukemic phase of Non Hodgkin's Lymphoma  Reactive lymphocytosis due to infections (EBV ,pertussis)  Metastatic tumors in bone marrow  ITP  AML
  • 12. Diagnostic work up  History & 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
  • 13.
  • 14. How does ALL classified? FAB WHO IMMUNOPHENOTYPIC
  • 15. 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
  • 16. FAB 1 Lymphoblasts: Small & Monomorphic
  • 17. FAB 2 Lymphoblasts: Large & Heterogeneous
  • 18. FAB 3 Large varied cells with vacuoles
  • 19. 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
  • 20. 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%
  • 22. Remission induction 4-6 weeks Intensification 6 months Maintenance therapy 2 years
  • 23.
  • 24. 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. Testes B. Spleen C. Bone marrow D. Brain
  • 25.  Q: which of the following targeted agents have been shown to be beneficial in adult ALL? A. Imatinib B. Alemtuzumab C. Gemtuzumab D. Sunitinib
  • 26. Questions?????  Does my patients cure?  There is possibility of relapse?  Does my patient need bone marrow transplant? And at which time?
  • 27. 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
  • 28. Timing of bone marrow transplant  Primary 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
  • 29. Prognosis favorableunfavorable ≤ 35 y>35 yAge ≤ 30 ,000 /mm>30,000 /mmWhite blood cell otherB-cell precursorImmunophenotype othert(9;22) t(4;11) t(1;19) Cytogenetics < 4 weeks> 4 weeksTime to complete response
  • 30. Survival Children • CR 97% • At 5 years DFS >75% Adult • CR 75-90% • 5 –years DFS 25-50%