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THE CHRONIC LEUKEMIAS CHRONIC LYMPHOCYTIC LEUKEMIA AND CHRONIC MYELOID LEUKEMIA

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THE CHRONIC LEUKEMIAS CHRONIC LYMPHOCYTIC LEUKEMIA AND CHRONIC MYELOID LEUKEMIA John Matthews What are the Chronic Leukemias? Neoplasms of either the myeloid or ... – PowerPoint PPT presentation

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Title: THE CHRONIC LEUKEMIAS CHRONIC LYMPHOCYTIC LEUKEMIA AND CHRONIC MYELOID LEUKEMIA


1
THE CHRONIC LEUKEMIAS CHRONIC LYMPHOCYTIC
LEUKEMIA AND CHRONIC MYELOID LEUKEMIA
  • John Matthews

2
What are the Chronic Leukemias?
  • Neoplasms of either the myeloid or lymphoid
    lineage which are capable of differentiation to
    mature cells.

3
Types of Leukemia
4
Acute versus Chronic Leukemia
5
Monoclonal B-cell Lymphocytosis
6
Chronic Lymphocytic Leukemia
7
US SEER data annual cases/100,000
8
CLL - Pathology
  • Genetic change in B-cell clone
  • Slow proliferation exceeds apoptosis
  • Gradual accumulation of neoplastic B-lymphocytes
    blood, marrow, nodes, spleen

9
CLL clinical features
  • Asymptomatic lymphocytosis
  • Marrow failure
  • Lymphadenopathy
  • Hepatosplenomegaly
  • B-symptoms
  • Immunodeficiency

10
CLL - blood count
WBC x 109/L 150 4-11 Hb g/L 98 120-160 M
CV fl 87 79-98 Platelets x
109/L 48 150-450 Neuts x 109/L 1.5 2-7.5
Lymphs x 109/L 130 1.5-4 Monos x
109/L 0.5 0.2-0.8 Eos x 109/L - 0-0.7 Ba
sos x 109/L - 0-0.1 Smudge Cells x
109/L 28 0 Film Comment lymphocytosis with
smudge cells appearances suggest CLL
11
Normal
lymphocytes
12
CLL
lymphocytes
smudge cells
13
CLL - Diagnosis
  • Increase in blood lymphocyte count
  • Demonstrate presence of a B-lymphocyte clone of
    appropriate immunophenotype
  • Surface marker analysis flow cytometry

14
CLL - complications
  • Opportunistic infection (e.g. shingles,
    pneumonia)
  • Autoimmune hemolytic anemia (10), autoimmune
    thrombocytopenia, pure red cell aplasia

15
CLL - principles of treatment
  • Watch and Wait
  • Chemotherapy

16
CLL - median survival (years)
  • Early - lymphocytosis alone (gt10y)
  • Late - marrow failure (3-4y)

17
CLL - prognosis
  • Stage
  • Genetic translocation
  • Mutation status of V-region genes

18
Figure 1. (A) Overall survival of patients with
CLL according to Binet stages (Barcelona series)
Montserrat, E. Hematology 20062006279-284
19
Probability of Survival from the Date of
Diagnosis among the Patients in the Five Genetic
Categories
Dohner H et al. N Engl J Med 20003431910-1916
20
Hamblin, T. J. et al. Blood 1999941848-1854
21
CHRONIC MYELOID LEUKEMIA A 2-PHASE DISEASE,
CHRONIC AND ACCELERATED (BLAST CRISIS), AND A
MAGIC BULLET
22
Chronic Myeloid Leukemia
  • A neoplasm of hemopoietic stem cells caused by
    the Philadelphia chromosome t(922)
  • A two-phase disease

23
(No Transcript)
24
Peter Nowell
25
(No Transcript)
26
(No Transcript)
27
1960
The findings suggest a causal relationship
between the chromosome abnormality observed and
chronic granulocytic leukemia.
28
The Philadelphia Chromosome
29
1973
Janet Rowley
30
(No Transcript)
31
(No Transcript)
32
fusion 22 bcr/abl
abl
bcr
fusion 9 abl/bcr
33
CML - clinical features of chronic phase
  • Peak age 20 to 40 years
  • Weight loss, night sweats
  • Big spleen
  • Gout
  • Often found by chance

34
CML - diagnosis
  • Blood count
  • Genetic analysis (RT-PCR or FISH)
  • Bone marrow in selected cases

35
CML - blood count
WBC x 109/L 122 4-11 Hb g/L 98.5 120-16
0 MCV fl 87 79-98 Platelets x
109/L 843 150-450 Neuts x 109/L 80 2-7.5
Lymphs x 109/L 2.0 1.5-4 Monos x
109/L 2.0 0.2-0.8 Eos x 109/L 1.0 0-0.7
Basos x 109/L 5.0 0-0.1 Metamyelocytes x
109/L 4.0 0 Myelocytes x 109/L 20.0 0 Pro
myelocytes x 109/L 4.0 0 Blasts x
109/L 2.0 0 Nucleated red cells x
109/L 2.0 0 Film Comment appearances
suggest CML
36
Normal
37
CML
blast
basophil
neutrophils and precursors
promyelocyte
38
CML - accelerated phase
  • Was inevitable now prevented by imatinib
  • 1/3 ALL 2/3 AML
  • Clinical features
  • sweats, weight loss, bone pain, enlarging spleen
  • bone marrow failure, and blasts in the blood
  • Onset and course rapid, outcome fatal.

39
CML - principles of treatment
  • Imatinib mesylate to achieve a Major Molecular
    Remission (by Q-RT-PCR)
  • Allogeneic transplantation
  • Hydroxyurea

40
CML - prognosis (median survival years)
  • No treatment (3)
  • Suppressive chemotherapy (4)
  • Imatinib mesylate (95 alive at 6 years)
  • Transplant (5)

41
Kaplan-Meier Estimates of the Rates of Event-free
Survival and Progression to the Accelerated Phase
or Blast Crisis of CML for Patients Receiving
Imatinib
Druker B et al. N Engl J Med 20063552408-2417
42
European BMT data 1980-90
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