FOR MEDICAL STUDENTS

1. LEUKEMIAS
Acute leukemias
Mulugeta A.(internist)

3. - Is a group of malignant (neoplastic) disorders , characterized
by the clonal expansion and accumulation of one or more
blood cell line(s) , with eventual involvement of all
hematopoietic organs and other organs.
Leukemia

4. Definition

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

6. .

13. i
d present;often
S

14. Is

15. Leukemia
Tow or more Mutations within the genome of HSC or multipotential
progenitors/precursors
Activation of specific proto-oncogene
De-activation of tumor suppressor genes
Clone of cells with characteristics of a malignant cell
• Prolonged life (immortal) resistant to apoptosis
• Growth factor independent growth
• Insensitivity to growth-inhibitory signals
• Ability to invade and metastasize
• Blockage of intracellular differentiation

17. Clinical Features of AL
AL presents acutely
Exception- transformed/secondary AL
In general patients manifest signs & symptoms related to
Abnormalities of the 3 blood cell lines
Infiltration of organs & tissues
Certain features are specific to the AL type
Family history of malignancy and history of predisposing factors should be
looked for.

18. Symptoms of AL
Sxs of anemia
Sxs of thrombocytopenia
Fever
High grade due to infections
Low grade with systemic sxs due to the AL
Sxs due to CNS involvement
Seizure, headache, cranial nerves dysfunction
Vomiting, blurring of vision, altered mentation
Abdominal fullness & other GI sxs due to
organomegaly and electrolyte disturbance
Oliguria

19. Signs of AL
Pallor
Bleeding
Mucocutaneous
DIC
Fever and other signs of infection accordingly

20. Signs ...
Signs of tissue or organ infiltration
Gingival hyperplasia
LAP
Hepatosplenomegaly
Bone(sternal tenderness)
Chloromas
Leukemic cutis
Cranial nerve palsies
Mengeal irritation signs
Extramedullary disease
Prominent LAP & signs of mediastinal LAP

22. Investigation in AL
Complete history and physical examination
CBC, differential, platelets, ESR, Blood group
Serological screening ( HIV, HBV, HCV, CMV...)
Examination of peripheral smear
BM aspiration & biopsy
Morphology
Flowcytometry
Cytochemical studies
Cytogenetic study

23. Investigation in AL...
CXR
Coagulation profile
Biochemical tests
Liver & renal functions
Serum electrolytes
Uric acid
Serum LDH
Serum lysozymes
Blood and other specimen for culture

24. Investigation in AL...
LP
CT Scan
HLA TYPING
Cardiac function ( ECG, ECHO)

25. Classification(AML)
FAB
Based on morphology & cytochemical studies
Blast % in the BM for Dx
Simple & still in wide clinical use but does not incorporate the recent advances in
molecular study
WHO
Comprehensive
Detail molecular and cytogenetic studies
Currently not universally applicable

26. Cllassifiication

27. Classification of ALL
FAB classification of ALL
L1, L2, L3
Based on the morphology of lymphoblasts
Less relevant in predicting outcome
Immunological classification of ALL
Based on cell marker and other studies
B or T cell variant with their stage of development
Comprehensive
Relevant in predicting outcome

29. in contrast to the
myeloblast, the
LYMPHOBLAST is
a small blast with
scant cytoplasm,
dense chromatin,
indistinct nucleoli,
and no auer rods

32. M0 Minimally differentiated AML 5% - 10%
Negative or < 3% blasts stain for MPO ,PAS and NSE
blasts are negative for B and T lymphoid antigens, platelet
10 - 20%
glycoproteins and erythroid glycophorin A.
M1 Myeloblastic without maturation
>90% cells are myeloblasts
3% of blasts stain for MPO
+8 frequently seen

34. Granules contain procoagulants
ostic

40. Homogenous small
lymphoblasts
Scant cytoplasm
Regular round
nuclei
Inconspicuous
nucleoli

41. ALL L2
Heterogenous
lymphoblasts
Variable cytoplasm
Cleft nuclei
Large nucleoli

42. Homogenous large
lymphoblasts
Vacuolated
cytoplasm
Round nuclei

43. Bone marrow failure
Organ
infiltration
1. Pallor, lethargy,
dyspnea
2. Bleeding
manifestations
3. Infections
4. fever
1. Pain & tenderness of
bones
2. Lymphadenopathy
3. Hepatosplenomagaly
4. Gum hypertrophy
5. Chloromas
6. Meningeal signs

45. Treatment
Requires comprehensive team & good setup
Starts with the confirmation of specific AL dx & prognostication.
In general has 2 important components
Supportive
Specific/ Definitive
Certain parameters/ goals related to specific therapy
Remission ( CR, PR)
Survival (leukemia free, overall survival, relapse )
Cure

46. Supportive Care
Recombinant growth factors (GM-CSF, G-CSF, EPO, IL-11, Thrombopoietin)
Hyperleukocytosis/hyperviscosity, leukostasis
Associated with various complications
Leukopheresis
Emergency irradiation of whole-brain
Adminstration of drugs for cytoreduction
 Hydroxyurea, steriods
Early dx & Rx of coagulation abnormality
Reverse-barrier ( reverse – isolation)

47. Supportive Care
Fluid & electrolyte management
Blood component therapy
Packed red cells transfusion
Platelet transfusion
Treatment of infection
Broad spectrum IV antibiotics( empiric/emergency)
 culture and other studies
Prevention of uric acid nephropathy & tumor lysis syndrome
hydration
Allopurinol & other agents

48. Supportive Care
Vascular access
Birth control and fertility advice
Treatment of comorbid conditions
Psychosocial support

49. Specific Treatment
Chemotherapy
Specific regimen of the AL types
Phases
 Remission Induction
 Postremission
Hematopoietic Stem Cell Transplantation
Allogeneic-SCT
Syngeneic-SCT
Autologous-SCT
Investigational Therapy
Clinical trails