1. Acute leukemia

2. Hematological malignancy in leukocyte cell lineage
Leukemia
Hematological malignancy in leukocyte cell lineage

4. Acute leukemia: outline
Concepts, biology
Epidemiology
Clinical and laboratory manifestations
Diagnosis
Management and prognosis

5. Classification of leukemias
Acute
Chronic
Myeloid origin
Acute Myeloid Leukemia (AML)
Chronic Myeloid Leukemia (CML)
Lymphoid origin
Acute Lymphoblastic Leukemia (ALL)
Chronic Lymphocytic Leukemia (CLL)

6. ALL AML Hematopoietic stem cell Neutrophils Eosinophils Basophils
Monocytes
Platelets
Red cells
Myeloid
progenitor
Lymphoid
B-lymphocytes
T-lymphocytes
Plasma
cells
germinal center
naïve
AML

7. Myeloid maturation MATURATION myeloblast promyelocyte myelocyte
metamyelocyte
band
neutrophil
MATURATION

8. accumulation of blasts in the marrow
Acute Leukemia
accumulation of blasts in the marrow

9. AML vs CML (dominant cells in the peripheral blood test)
Myeloid cell CML AML normal
blasts q q
promyelocytes q
myelocytes q
metamyelocytes q
bands q
neutrophils q q

10. Adult acute leukemia Hematologic urgency
Usually fatal within weeks-months without chemotherapy
With treatment, high mortality due to disease or treatment-related complications (unlike childhood acute leukemia)

11. Classification of acute leukemias
ALL
mainly children
Male > Female
curable in 70% of children
curable in minority of adults
AML
mainly adults
Male > Female
curable in minority of adults

12. Two-hit model of leukemogenesis
Loss of function of transcription factors needed for differentiation
eg. AML1-ETO
CBFb-SMMHC
PML-RARa
Gain of function mutations of tyrosine kinases
eg. FLT3, c-KIT mutations
N- and K-RAS mutations
BCR-ABL
TEL-PDGFbR
differentiation
block
enhanced
proliferation
Acute
Leukemia +

13. Causes of acute leukemias
idiopathic (most)
underlying hematologic disorders
chemicals, drugs
ionizing radiation
viruses (HTLV I)
hereditary/genetic conditions

14. Clincal manifestations
symptoms due to:
marrow failure
tissue infiltration
leukostasis
constitutional symptoms
other (DIC)
usually short duration of symptoms

15. Marrow failure neutropenia: infections, sepsis anemia: fatigue, pallor
thrombocytopenia: bleeding

16. Infiltration of tissues or organs
enlargement of liver, spleen, lymph nodes
gum hypertrophy
bone pain
other organs: CNS, skin, testis, any organ
gum hypertrophy

17. Chloromas A B C
NEJM 1998

18. Leukostasis
accumulation of blasts in microcirculation with impaired perfusion
lungs: hypoxemia, pulmonary infiltrates
CNS: stroke
Blast ≥ 50 x 109/L

20. Constitutional symptoms
fever and sweats common
weight loss less common

21. Laboratory features WBC usually elevated, but can be normal or low
blasts in peripheral blood
normocytic anemia
thrombocytopenia
neutropenia
DIC

22. Bone marrow examination
determining type
prognosis
Acute leukemias: presence of > 20% blasts in bone marrow

23. Distinguishing AML from ALL
light microscopy
AML: Auer rods, cytoplasmic granules
ALL: no Auer rods or granules.
flow cytometry
special stains (cytochemistry)

24. AML

25. AML

26. Auer rods in AML

27. ALL

28. FAB (1976) Classification for AML
M0 -- Undifferentiated AML
M1 -- AML without maturation
M2 -- AML with maturation
M3 -- Acute Promyelocytic Leukemia
M4 -- Acute Meylomonocytic Leukemia
M5 -- Acute Monocytic Leukemia
M6 -- Erythroleukemia (DiGuglielmo’s)
M7 -- Megakaryoblastic Leukemia

29. FAB classification for ALL
Subtype Morphology Occurrence (%)
L1 Small round blasts
clumped chromatin
L2 Pleomorphic larger blasts 20
clefted nuclei, fine chromatin
L3 Large blasts, nucleoli,
vacuolated cytoplasm

30. FAB Classification of ALL
L1: mostly in children
L2: mostly in adults
L3: “Burkitt” large basophilic B-cell blasts with vacuoles

31. Treatment of acute leukemias
Choice of Regimen is influenced by:
type (AML vs ALL)
age
curative vs palliative intent

32. Principles of treatment
combination chemotherapy
first goal: complete remission
further regimen to prevent relapse
supportive medical care
transfusions, antibiotics, nutrition
psychosocial support
patient and family

33. Chemotherapy for acute leukemias
Phases of ALL treatment
induction
intensification
CNS prophylaxis
maintenance
Phases of AML treatment
consolidation (post-remission therapy)
post-remission therapy

34. Hematopoietic stem cell transplantation
permits “rescue” from otherwise excessively toxic treatment
additional advantage of graft-vs-leukemia effect in allogeneic transplants
trade-off for allogeneic transplantation: greater anti-leukemic effect but more toxic

35. Prognosis
Adult AML
Adult ALL
similar to or worse than AML