3. Leukaemia : Malignant transformation of blood forming cells
Classification of Leukaemia:
Based on natural history :
Acute Leukaemia
Chronic Leukaemia
Based on cell type
Myeloid
Lymphoid
Based on release mechanism
Leukaemia : TLC increased with blast > 20% in peripheral blood
Sub leukemic leukaemia: TLC < 4000/dl, few blast in peripheral blood Marrow shows
Aleukaemic leukaemia : TLC <4000/dl , no blast in peripheral blood >20% blast
I. Acute Lymphoblastic leukemia (ALL)
II. Acute Myeloblastic leukemia(AML)
Age distribution of Leukaemia
4. Acute Leukaemia
Definition:
Short duration of symptoms
Malignant ds of bone marrow stem cells….arise in marrow…. Spread to blood
Bone marrow: Blast cells>20% (WHO Criteria)
diffusely replaced with proliferating neoplastic blast cells
PS: Abnormal number and immature forms of blood cells
Type of leukaemia is Identified by company they keep
Classification:(FAB)
Acute Lymphoblastic leukaemia (ALL)
Acute Myeloblastic leukaemia(AML)
5. Myeloblast
Size :3-5 time large than lymphocyte
Nuclear chromatin : Uniform ,fine
Nucleoli :3-5 ,prominent
Cytoplasm : Scanty – moderater
Cytoplasm granules: +/-
Auer Rods : +/-
Cells accompany:
Promyelocyte ,myelocyte,MM
Cytochemistry:
MPO/ Sudan black : Positive
PAS: Negative
NSE: Positive in M4,M5
Lymphoblast
Size :2- 3 time large than lymphocyte
Nuclear chromatin : Uniform ,coarse
Nucleoli :1-2 ,prominent
Cytoplasm : Scanty (< than myeloblast)
Cytoplasm granules: - Agranular
Auer Rods : not seen
Cells accompany:
Lymphocyte
Cytochemistry:
MPO/ Sudan black :Negative
PAS: Block Positive
NSE: Negative
6. Cytochemistry in leukaemia:
Enzyme (Myeloperoxidase, NSE) chemical present in cell cytoplasm
Non enzyme substance (lipid , glycogen)
Myeloperoxidase – stains MPO enzyme in primary granules of mature & immature
cells of myeloid series (+ in AML M1,M2,M4 blast & Auer rod)
Sudan Black B – Stains phospholipids in granules of myeloid series
Nonspecific esterase- enzyme present in monocytic series cells (+ AML M4 & M5)
Periodic Acid –Schiff (PAS) reaction – stains glycogen in cytoplasm
(+ in ALL[ALL L1 Block positivity] & AML M6,M7)
Leucocyte alkaline phosphatase : enzyme present in specific granules in cytoplasm of
mature neutrophils
MPO Posiive in AML PAS Positive Block In ALL
7. Acute Myelogenous Leukaemia:
Def :Neoplasm of hematopoietic progenitors…proliferation & accumulation of
myeloblast & immature myeloid series cells in marrow
C/F: Adults (15-60years)
Onset : Abrupt
Symptoms:
Bone Marrow Failure
Anemia : weakness & fatigue
Neutropenia : Frequent bacterial/fatal infections/ opportunistic infections
Thrombocytopenia: Petechae, bleeding ,Disseminated Intravascular Coagulation (AML M3)
Bony pain & tenderness
Extra medullary / organ infiltration
Myeloid sarcoma/ chloroma [green in colour]/Granulocytic sarcoma
:Sites(skin ,lymph node, GIT , soft tissue
Gingival hypertrophy(AML M4& M5)
Hepatospleenomegaly
Prognosis: Fulminant,
Cytogenetic markers : major determinants of outcome
10. Lab Findings:
Haemoglobin : Decrease ,
PS : RBC- N/N
WBC: TLC: Markedly raised, Myeloid blast > 20%,Auer rods + in M2-M3
Platelet: Moderate to severe thrombocytopenia
Cytochemistry : MPO :+ , NSE: + with monocyte cells
Bone Marrow: Cellularity: Increased markedly
Erythropoiesis : suppressed
Myelopoiesis: > 20 % blast , presence of immature cells
Megakaryopoiesis: Decreased
Immunophenotyping in WHO classification 2016
Cytogenetics
Myeloblast Promyelocyte with auer rods Myelomonocytic cells
11. Acute Lymphoblastic Leukaemia
Def : Neoplastic proliferation of lymphoblast
C/F:
Age: Children of 1-5Yrs (>85% B ALL)
Adolescent male as mediastinal ,thymic mass(15% T ALL)
Onset : abrupt
Symptoms:
Bone marrow failure :
Anemia : weakness & fatigue
Neutropenia : Frequent bacterial/
fatal infections/ opportunistic infections .
Sore throat & Respiratory infections
Thrombocytopenia: bleeding
Bony pain & tenderness
Extra medullary / organ infiltration
Lymphadenopathy (>75%,cervical >)
CNS Involvement(ALL-Pre B)
Testicular Involvement (ALL)
Hepatospleenomegaly
13. Prognosis: in ALL is Far better than AML
Good Prognostic Markers in ALL
1) Age 2-10yrs
2) Females
3) TLC < 50,000cells/cumm
4) No meningeal involvement
5) Hyperploidy , trisomy 4,7,10 & t(12;21)
6) Clearing of blast from blood after chemotherapy <1week
14. Lab Findings:
Haemoglobin : Decrease ,
PS : RBC- N/N
WBC: TLC: Markedly raised, Lymphoblast > 20%,
Platelet: Moderate to severe thrombocytopenia
Cytochemistry : PAS : Block like positivity +
Bone Marrow: Cellularity: Increased markedly
Erythropoiesis : suppressed
Myelopoiesis: > 20 % blast , presence of lymphoblast
Megakaryopoiesis: Decreased
Immunophenotyping : TdT +(Pre B & Pre T lymphoblast),
B-ALL(CD10 & CD 19 )
T-ALL(CD2,CD5,CD8)
Biochemical : LDH : raised due to increase leukemic cell turn over
Uric Acid: Raised after chemotherapy
CSF Examination : To R/O Meningeal involvement & for staging
15. Chart showing difference between
Acute Lymphoblastic Leukaemia Acute Myeloblastic Leukaemia
Parameter ALL AML
1.Predominant age Children ( peak 3-4yrs) Adults (15-60yrs)
2.Morphology of Blast
Nuclear chromatin
Nucleoli
Cytoplasm
Cytoplasm granules
Auer Rods
Cells accompany
Uniform ,coarse
1-2 ,prominent
Scanty (< than myeloblast)
- Agranular
not seen
Lymphocyte
Uniform ,fine
3-5 ,prominent
Scanty – moderater
+/-
+/-
Promyelocyte,myelocyte
3.Cytochemistry:
1. MPO/ Sudan black
2. PAS
3. NSE
Negative
Positive
Negative
Positive
Negative
Positive in M4,M5
4.Immunophenotyping B or T lymphoid markers Myeloid Markers
5.Prognosis Good Poor