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CML CML vs Leukemoid Reaction Chronic Lymphocytic

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Title: CML CML vs Leukemoid Reaction Chronic Lymphocytic


1
Lecture plan
  • Normal
  • Pathology
  • White cell disorders
  • Non neoplastic Abnormalities
  • ?in - Penias ? - Philias
  • Neoplastic disorders
  • Premalignant conditions
  • Myelodysplastic syndromes
  • Myeloproliferative disorders
  • Malignant or Leukemias
  • Acute Chronic
  • Myeloid Lymphoid
  • Hairy cell leukemia
  • Plasma cell neoplasms

2
Myelodysplastic Syndromes
  • Group of Clonal stem cell disorders
  • Characterized by
  • Maturation defect ? Ineffective Hematopoiesis
  • ?risk of Acute Myeloid Leukemias (AML)
  • Types
  • Primary or Idiopathic gt 50yrs, Gradual in
    onset,
  • risk of AML ?
  • Rx ( RT or Drugs) related (t MDS) after 2 -8 of
    RX, complication of Rx, Higher risk of AML (? ?
    ?)
  • Pathogenesis
  • Unknown

3
Myelodysplastic Syndromes
  • Cytogenetic abnormalities
  • Deletions (5q,7q,20q), Monosomy (5 7), Trisomy
    (8)
  • Morphology
  • Marrow usually Hypercellular,
  • Erythroid precursors - ring Sideroblasts, budding
    nucleated cells,
  • Granulocytic Megaloblastoid, Pseudo Pelger
    Huet neutrophils( two nuclear segments),
  • Megakaryocytes- Pawn ball type( multinucleate)
  • Peripheral Blood Cytopenias ( Pancytopenia)
  • Patients present with Refractory Anemias (not
    responding to hematenics even after 6 months of
    Rx )

4
Myelodysplastic Syndromes
  • FAB classification
  • RA Refractory Anemia (Blasts lt1)
  • RARS RA with Ring Sideroblasts (lt1)
  • RAEB RA with excess blasts (lt5)
  • RAEB in T RAEB in transformation (gt5)
  • Clinically
  • Anemia- weakness
  • Leukopenia- Infection ( sore throat)
  • Thrombocytopenia- Hemorrhages (patechae, Purpura)

5
MDS - Dysplastic Erythroblasts
6
MDS - Ring Sideroblast
7
Myeloproliferative Disorders
  • Disorders of multipotent progenitor cells (
    myeloid Lymphoid precursor)
  • Increased, Functionally abnormal cells.
  • Extramedullary hemopoiesis - Organomegaly
  • End stage
  • Progress to Leukemia
  • Myelofibrosis
  • Classification
  • Polycythemia rubra vera (PV)
  • Essential Thrombocythemia (ET)
  • Myelofibrosis (MF)
  • Chronic Myeloid Leukemia (CML)

8
MDS MPD
  • MDS
  • Myeloid cells
  • Marrow Hypercellular ( can be normal or hypo
    also)
  • Peripheral Cytopenias
  • Risk of Acute Leukemia
  • Organomegaly may not
  • No Spent phase
  • MPD
  • Mostly Myeloid also Lymphoid cells
  • Marrow Hypercellular
  • Peripheral Philias or cytosis
  • Risk of Acute Leukemia
  • Organomegaly (splenomegaly)
  • Spent phase (Fibrosis)

9
PV - Natural History
  • Indolent
  • ?Hgb, Hct ? ?blood viscosity ?Thrombosis (DVT)
  • lt 25 progress to ?
  • Marked BM fibrosis (spent phase)
  • Acute leukemia (2-15)
  • Rx of symptoms (i.e. phlebotomy)

10
Essential Thrombocythemia
  • ? platelets - episodic symptoms
  • Bleeding /
  • thrombosis
  • infections
  • Acute leukemia
  • (lt 1)

11
Myelofibrosis
12
Myelofibrosis - Natural History
  • Initial cellular phase
  • Progressive BM fibrosis / failure
  • Infection
  • Hemorrhage
  • Acute leukemia
  • (lt 10)

13
Lecture plan
  • Normal
  • Pathology
  • White cell disorders
  • Non neoplastic Abnormalities
  • ?in - Penias ? - Philias
  • Neoplastic disorders
  • Premalignant conditions
  • Myelodysplastic syndromes
  • Myeloproliferative disorders
  • Malignant or Leukemias
  • Acute Chronic
  • Myeloid Lymphoid
  • Hairy cell leukemia
  • Plasma cell neoplasms

14
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15
Leukemia Classification
  • Acute Leukemias
  • Acute Myeloid Leukemia - AML
  • AML M0, M1, M2, M3, M4, M5, M6 M7
  • Acute Lymphoid Leukemia - ALL
  • ALL - L1, L2 L3 - maturity
  • Chronic Leukemias
  • Chronic Myeloid Leukemia- CML
  • Chronic Lymphoid Leukemia - CLL

16
Leukemias
17
Blasts
18
Acute Leukemia
  • Untreated - patients survive lt6 months
  • Age predominance
  • ALL - children (peak- 4 yrs)
  • AML - adults (median age 50 yrs)

19
ALLCervical Lymphadenopathy
20
Organomegaly
21
ALL-Acute Lymphocytic Leuk.
  • Common in Children.
  • FAB classification L1, L2 L3(PAS- )
  • Pre B cell type common.
  • Growth failure, Fever, Anemia Lymphadenopathy,
    bleeding.
  • Moderate Hepatosplenomegaly
  • tdt CALLA (CD 10) Positive
  • Reservoir- Brian Testes

22
AML-Acute Myeloid Leukemia
  • Adults common ( 15 39 yrs age)
  • FAB classification - M0 to M7.
  • Anemia, Fever, Bleeding
  • Hepatosplenomegaly moderate
  • No significant lymphadenopathy

23
Myeloblasts Myeloperoxidase (MPS) positive
24
AML3- Acute Promyelocytic Leukemia
  • Hypergranular promyelocytes
  • Increased Auer rods
  • DIC from tissue thromboplastin
  • 1517 chromosomal translocation
  • (retinoic acid receptor gene)

25
AMLM3 - Auer Rods
26
AML-M5 - Gum Hypertrophy
27
AML 5 Non-specific Esterase
AML 5
Control
28
AML - summary
  • Mo- undifferentiated, Ultra structurally
    Myeloblasts
  • M1- No maturation, /gt3Blasts MPO ve
  • M2- MC(30-40), Auer rods, t(821)
  • M3- APML, many Auer rods/cell, Younger age ( 35
    yrs), DIC, t(1517)
  • M4- Myelomonocytic, NSE ve, inv(16)
  • M5- Monocytic (MPO-Neg, NSE-Pos), older pts,
    Organomegaly, Lymphadenopathy, Tissue
    infiltration ( skin- Chloromas),
  • M6- Erythro, older age, 20 of Rx related AMLs
  • M7- Megakaryocytic- Myelofibrosis

29
Chronic Myeloid Leukemia
  • Middle age 40-60y
  • Philadelphia chromosome, t(922)
  • c-abl (Abelson) chromosome 9 bcr (break point
    cluster region) chromosome 22 ?Protein with
    tyrosine kinase activity - plays
  • Anemia, Fever Bleeding
  • Marked Leukocytosis gt50,000 (abnormal)
  • Marked splenomegaly, Hepatomegaly
  • Clinical course
  • progressive ? accelerated phase ? 80 blast
    phase (AML or ALL)

30
CML
31
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32
CML vs Leukemoid Reaction
33
Chronic Lymphocytic Leukemia
  • Elderly age
  • Anemia, fever bleeding slow over years.
  • Lymphocytosis Lymphadenopathy
  • Spleen, liver enlargement
  • Common B cell
  • Spectrum of disease
  • CLL-Blood
  • SLL ( Small cell lymphocytic lymphoma)- Lymph node
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