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
(No Transcript)
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
(No Transcript)
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