Chronic Leukemia Lecture.

Chronic leukemia
ILOs
At the end of lecture, you should be able to:
❑ Define chronic myeloid and lymphoid leukemia.
❑ Mention Clinical presentation of chronic Leukemia
❑ How to diagnose chronic leukemias.
❑ Compare between chronic myeloid and lymphoid leukemia as regard

diagnosis and treatment.
❑ Know how we treat newly diagnosed patients with chronic leukemia.

Introduction
Blood cell development
AML ALL
CML
CLL
Myeloid maturation
myeloblast promyelocyte myelocyte metamyelocyte band neutrophil
MATURATION
Adapted and modified from U Va website

Classification of leukemias
Acute Chronic
Myeloid Acute Myeloid Chronic Myeloid Leukemia

Leukemia (AML) (CML)
Origin
Lymphoid Acute Lymphoblastic Chronic Lymphocytic Leukemia

Leukemia (ALL) (CLL)
Origin
Definitions;
• CML: dysregulated production and uncontrolled proliferation

of maturing granulocytes with fairly normal differentiation.
• CLL: progressive accumulation of functionally incompetent

mature lymphocytes, which are monoclonal in origin
Epidemiology;
CML CLL
Incidence in adult; 15-20% Most common in
Western
Median age of 50 70
diagnosis in adults:
Male : Female Slightly more More frequently in

frequently in males males
Risk factors;
CML CLL
Environmental factors Exposure to ionizing No clearly discernible

radiation is the only occupational or
known risk factor. environmental risk
factors that predispose
to CLL.
Genetic abnormalities Occur with higher than

expected frequency
among first-degree
family members
Clinical Features
Clinical features:
❑ Bone marrow:
• Overcrowding by abnormal cells
• Inadequate production of normal
marrow elements
• Anemia, thrombocytopenia, ↓ number
and function of WBCs
❑ Peripheral tissues:
Infiltration by malignant cells
Clinical features:
Anaemia Infiltration or Auto-immune →

Fatigue
Neutropenia (OR immuno- Recurrent infections
deficiency disorder)
Thrombocytopenia Infiltration or Auto-immune →

Bleeding episodes.
Bone pain Acute gouty arthritis (Sometimes

seen)
B-symptoms May present.
Clinical features, Cont.;
Hepatomegaly, Left upper quadrant pain, and

splenomegaly early satiety.
lymphadenopathy Firm, rounded, discrete, non-
tender, and freely mobile upon
palpation. More in CLL
Central nervous system Neurological manifestation
Skin Most commonly involved non-

lymphoid organ in CLL.
CLL
CML
Diagnosis
18
Chronic Myeloid Leukemia

Diagnosis
◼ Blood count
◼ Leukocytosis with a white count reaching upto 100,000/microL (range 12
to 1000/microL).
◼ Absolute basophilia is a universal finding in the blood smears from CML patients, and
absolute eosinophilia is seen in about 90 percent of cases.
◼ The platelet count can be normal or elevated
◼ Blood film:
◼ Shows virtually all cells of the neutrophilic series, from myeloblasts to mature
neutrophils with peaks in the percent myelocytes and segmented neutrophils.
◼ Blasts typically account for less than 2 percent.
◼ The presence of a greater percent of myelocytes than the more mature
metamyelocytes ("leukemic hiatus" or "myelocyte bulge") is one of the classic
findings in CML.
◼ Bone marrow aspirate & trephine:
◼ Hypercellular,
◼ Granulocytic hyperplasia with a maturation pattern that reflects that
seen in the peripheral smear.
◼ Other non-specific bone marrow findings include an increase in
reticulin fibrosis and vascularity.
◼ Hyperuricemia and hyperuricosuria
◼ Serum vitamin B12-binding proteine and serum vitamin B12
levels are increased
◼ Cytogenetic test- presence of the Ph chromosome
◼ Molecular test – presence of the BCR-ABL fusion gene
The Philadelphia (Ph) chromosome
Features of Patients with Newly Diagnosed
Philadelphia Chromosome–Positive Chronic
Myelogenous Leukemia in Chronic Phase
Accelerated phase of CML
❑ Most patients eventually became resistant to therapy and the

disease enters a more agressive phase
❑ Criteria of accelerated phase
✓ Blasts in blood or bone marrow-10-19%
✓ Basophilia ≥ 20%
✓ Thrombocytopenia <100G/l unrelated to ttt
✓ Thrombocytaemia >1000G/l unresponsive to ttt
✓ Additional chromosomal aberrations
✓ refractory splenomegaly or refractory leucocytosis
Blast phase (blast crisis) of CML
❑Criteria of blast phase

✓ Blasts in blood or bone marrow ≥20%
✓ extramedullary tumors
✓ Large foci or clusters of blasts in BMB
Differential diagnosis
❑ leukemoid reaction:
syndrome with morphologic changes similar to leukemia in
peripheral blood usually 2ry to infections as T.B., pneumonia,
meningitis or metabolic causes. But:
✓ Eosinophils and bosophils are decreased (rather than
increased).
✓ WBCs are alkaline phosphatase stongly +ve (rather than -
ve).
✓ B.M. is only moderately hyperplastic
❑ Other myeloproliferative neoplasms

29
Chronic Lymphocytic Leukemia

❑ CBC:
WBC:.
Diff: lymphocytosis ,the absolute lymphocyte count is>5x109/l and
may be up to 300x109/l or more.
Anemia : normocytic normochromic anemia is present in later
stages,autoimmune haemolysis.
Platelets : thrombocytepenia may occur.
❑ Blood film:
70-99% of white cells mature lymphocyte.
Smudge or smear cells also present.
❑ Immunophenotyping:
Shows that the lymphocyte are B cells(CD19)expressing one form of
light chain( or only)cells are also CD5 & CD23 are both +ve.
❑ Bone marrow aspiration:
Lymphocytic replacement of normal marrow.
❑ Immunoglobulin electrophoresis:
of Ig more marker with advance disease.
❑ Cytogenetic :
The 4 most common abnormalities are; deletion
of13q14,trisomy 12,deletion of11q23&structural abnormality
of 17p involving the p53 gene.
33
Staging :
❑ Staging is very important for prognosis and

treatment.
❑ There are two staging system(Rai and Binet).

34
A-Rai Classification:
Stage definition
0 Absolute lymphocytosis.
1 Stage 0+enlarged lymph nodes.
11 Stage 0+liver or/and spleen   adenopathy.
111 Stage 0+anemia organomegally or adenopathy.
1V Stage 0+thrombocytopenia organomegally or adenopathy.

B-Binet Classification:
Stage . Organomegally Hb Platelet.

.
A < 3 areas 10 100
B >3 areas 10 100
C Not considered <10 and /or

<100
35
Differential diagnosis
❑Other causes of:

▪ Lymphadenopathy
▪ Splenomegaly
▪ Hepatomegaly
▪ Immune anemia or thrombocytopenia

Management
38
Chronic Myeloid Leukemia

Overview
❑Supportive ttt: hydration, uricosiric drugs….
❑Oral chemotherapeutic agents (hydroxyurea,

busulfan)
❑Interferon alfa
❑BCR-ABL tyrosine kinase inhibitors (TKIs), such

as imatinib , dasatinib , and nilotinib .
❑Allogeneic hematopoietic cell transplantation (HCT).

Tyrosine kinase inhibitors
2. Stem cell transplantation;
◼ Allogeneic stem cell transplantation.
◼ Autologous stem cell transplantation.

42
Chronic Lymphocytic Leukemia

Treatment :
❑ Not all patients will require active ttt
❑ Indication for treatment:

✓ Huge organomegaly or LN.
✓ Hemolytic episodes.
✓ Bone marrow suppression.
✓ Severe constitutinal symptoms
✓ Rapid lymphocyte doubling time
A. Supportive care:
◼ Anemia – red cell transfusion
◼ Thrombocytopenia – platelet concentrates
◼ Infection – broad spectrum IV antibiotics + IVIG
◼ Hematopoietic growth factors : GM-CSF, G-CSF
◼ Metabolic problems:
◼ Monitoring hepatic / renal / hematologic function;
◼ Fluid & electrolyte balance, nutrition Hyperuricemia- hydration, Allopurinol
◼ Psychological support.
Modality of Treatment:
1-Chemotherapy:
❑ Chlorambucil: 6mg/m2 daily for 10 days monthly for 2-4
month after which remission will be obtain.
❑ Fludarabine: more effective as single agent.
❑ Corticosteroid : indicated in autoimmune hemolytic anemia

and thrombocytopenia.
2-Radiotherapy:
Is useful in reducing the size of LN not responsive to chemo.
45
Cont:
3-Monoclonal antibody:
Both campath (anti CD52)and Rituximab(anti CD20)produce
response in proportion of patient.
4-Splenectomy :
For immune-mediated cytopenia or painful bulky splenomegally.
5-immunoglobulin replacement:
for patient with hypogammaglobulinemia and recurrent infection.
6- Stem cell transplant:

Useful in some patients
46
Thank you

Chronic Leukemia Lecture.

Uploaded by

Copyright:

Available Formats

Chronic Leukemia Lecture.

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Chronic Leukemia Lecture.

Uploaded by

Copyright:

Available Formats

Chronic leukemia

❑ Define chronic myeloid and lymphoid leukemia.

❑ Mention Clinical presentation of chronic Leukemia

❑ How to diagnose chronic leukemias.

❑ Compare between chronic myeloid and lymphoid leukemia as regard

❑ Know how we treat newly diagnosed patients with chronic leukemia.

myeloblast promyelocyte myelocyte metamyelocyte band neutrophil

Adapted and modified from U Va website

Myeloid Acute Myeloid Chronic Myeloid Leukemia

Lymphoid Acute Lymphoblastic Chronic Lymphocytic Leukemia

• CML: dysregulated production and uncontrolled proliferation

• CLL: progressive accumulation of functionally incompetent

Male : Female Slightly more More frequently in

Environmental factors Exposure to ionizing No clearly discernible

Genetic abnormalities Occur with higher than

Anaemia Infiltration or Auto-immune →

Thrombocytopenia Infiltration or Auto-immune →

Bone pain Acute gouty arthritis (Sometimes

Hepatomegaly, Left upper quadrant pain, and

Central nervous system Neurological manifestation

Skin Most commonly involved non-

Chronic Myeloid Leukemia

❑ Most patients eventually became resistant to therapy and the

❑Criteria of blast phase

❑ Other myeloproliferative neoplasms

Chronic Lymphocytic Leukemia

❑ Staging is very important for prognosis and

❑ There are two staging system(Rai and Binet).

1 Stage 0+enlarged lymph nodes.

11 Stage 0+liver or/and spleen   adenopathy.

111 Stage 0+anemia organomegally or adenopathy.

1V Stage 0+thrombocytopenia organomegally or adenopathy.

Stage . Organomegally Hb Platelet.

B >3 areas 10 100

C Not considered <10 and /or

❑Other causes of:

▪ Immune anemia or thrombocytopenia

Chronic Myeloid Leukemia

❑Supportive ttt: hydration, uricosiric drugs….

❑Oral chemotherapeutic agents (hydroxyurea,

❑BCR-ABL tyrosine kinase inhibitors (TKIs), such

❑Allogeneic hematopoietic cell transplantation (HCT).

◼ Allogeneic stem cell transplantation.

◼ Autologous stem cell transplantation.

Chronic Lymphocytic Leukemia

❑ Not all patients will require active ttt

❑ Indication for treatment:

◼ Anemia – red cell transfusion

◼ Thrombocytopenia – platelet concentrates

◼ Infection – broad spectrum IV antibiotics + IVIG

◼ Hematopoietic growth factors : GM-CSF, G-CSF

◼ Monitoring hepatic / renal / hematologic function;

◼ Fluid & electrolyte balance, nutrition Hyperuricemia- hydration, Allopurinol

❑ Fludarabine: more effective as single agent.

❑ Corticosteroid : indicated in autoimmune hemolytic anemia

6- Stem cell transplant:

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.