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Understanding Chronic Myelogenous Leukemia

Chronic myelogenous leukemia (CML) is a type of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow. It results from a specific genetic mutation that produces the Philadelphia chromosome. The diagnosis of CML involves blood tests, bone marrow biopsy, and genetic testing to detect the Philadelphia chromosome and the associated BCR-ABL gene. Treatment of CML involves the use of tyrosine kinase inhibitors such as imatinib to target the abnormal BCR-ABL protein. The goals of treatment are hematologic, cytogenetic and molecular remission to suppress the disease. Prognosis depends on factors like time to remission and response to therapy.

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104 views28 pages

Understanding Chronic Myelogenous Leukemia

Chronic myelogenous leukemia (CML) is a type of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow. It results from a specific genetic mutation that produces the Philadelphia chromosome. The diagnosis of CML involves blood tests, bone marrow biopsy, and genetic testing to detect the Philadelphia chromosome and the associated BCR-ABL gene. Treatment of CML involves the use of tyrosine kinase inhibitors such as imatinib to target the abnormal BCR-ABL protein. The goals of treatment are hematologic, cytogenetic and molecular remission to suppress the disease. Prognosis depends on factors like time to remission and response to therapy.

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jourey08
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Sahyuddin

Div. of Hematology & Medical Oncology


[Link] Internal Medicine, Medical Faculty
Hasanuddin University
Contents

1 What is CML ?

2 How is the pathophysiology of CML ?

3 How to diagnosis CML ?

4 How to manage patient with CML ?


I. Chronic Myelogenous Leukemia (CML)

increased proliferation of granulocytic cell

CML without the loss of their capacity to diff.

increased number of granulocytes


I. Chronic Myelogenous Leukemia (CML)

Chronic Myelogenous Leukemia ( CML )


- Belongs to Myeloproliferative Disorders
- Adult & elderly
- Relatively slow clinical progression
- Relatively better live expectancy than
acute leukemia.
I. Chronic Myelogenous Leukemia (CML)

few cancers known to be caused by


a single, specific genetic mutation.

CML
> 90% a cytogenetic aberration
Ph chromosome
I. Chronic Myelogenous Leukemia (CML)
2. Accelerated phase :
[Link] stable - Blasts 10-19% of wBC
phase (CP): in peripheral & BM
- blast < 10% in - Persistent
the blood & BM thrombocytopenia
- 85% pts dx/ in CP
CML (< 100 109/L)
(WHO) - persistent
- Progres to AP & BP thrombocytosis
after 3-5years (> 1000 109/L)
- Increasing white blood
cells & spleen size

3. Blast crisis :
- Blasts 20% of peripheral blood WBC or BM
- Extramedullary blast proliferation
- Large foci or clusters of blasts on bone marrow
biopsy
II. Etiology of CML :

Not clear yet.


- Cytotoxic drugs ?
- Viruses ?
- Radiation ?
- Pollutants ?
III. Pathogenesis of CML :

Majority : Philadelphia chromosome (+)


t (9:22) : resiprocal transversion of genetic
material from chrom 9 to 22 (vv)
new abnormal protein
initiating abnormal proliferation of
myeloid cells in bone-marrow CML.
III. Pathophysiology
Three-hit model of leukemogenesis

Gain of function mutations


of tyrosine kinases Loss of Apoptosis

eg. FLT3, c-KIT mutations eg.:


N- & K-RAS mutations
BCR-ABL Bcl-2 over expression
TEL-PDGFbR

enhanced Normally Suppression


proliferation + differentiation + apoptosis

Chronic
Leukemia
III. Diagnosis of CML

Physic
Hemato

Anamnesis CML

Cytogen

BCR-ABL
Trias CML

Splenomegali

ADT : Pasar Malam Diagnosis CML

Pemeriksan BCR-ABL
Targeting terapi (TKI) :
- Imatinip mesylate (Glivec)
- Nilotinib (Tasigna)
- Dasatinib
III. The Diagnosis of CML +
III. The Diagnosis of CML +
[Link] of CML
III. Diagnosis of CML

CP AP BP
III. Diagnosis of CML

Cytogenetic
III. Diagnosis of CML

BCR-ABL
IV. Management of CML

The goals of treatment of CML

1 2 3
[Link] [Link] 3. Molecular
remission remission remission
(normal (normal (negative of
complete chromosome) polymerase
bloodcell , chain reaction
count (CBC), (PCR) &
negative of the
mutational
BCR/ABL
mRNA)
IV. Management of CML

1. Cytoreduksi Agents

2. Tyrosine kinase inhibitors

3. Leucopharesis

4. Transplantation
IV. Management of CML

Historis Terapi CML


1. Cytoreduksi Agents :
Th 1959 : Busulfan (Myleran)
Th 1969 : Hydroxyurea fase lekositosis atau
trombositosis.
Th 1990 an : Interferon- (IFN) gold standard sampai
diperkenalkannya Tyrosine Kinase Inhibitors (TKI)
2. Tyrosine kinase Inhibitors (TKI)
Imatinib (first TKI & gold standard /terapi lini pertama)
TKI generasi ke 2 : Nilotinib & Dasatinib
( approved sbg lini kedua, kemudian juga utk lini pertama )
IV. The Management of CML
IV. Management of CML
IV. Management of CML

Leucopharesis:

1. Severe leukositosis

2. Complication (leukostasis)
IV. Management of CML

Splenectomy and splenic irradiation :


patients with large and painful spleens,
usually in the late phase of CML.

splenectomy is associated with high perioperative


morbidity and mortality rates because of bleeding
or thrombotic complications.
IV. Management of CML

New technic :
Peripheral Blood Stem-cell
Transplantation ( PBSCT )
Advantages :
- no need operating theatre
- relatively simple & easy procedure
- low cost
- most ideally procedure (?)
V. Prognosis

Prognosis depend on clinical & lab. Factor

Prognosis depend on therapy associated


factors:

1. Time to hematology remission


2. Duration of remission
3. Total dose of chemotherapy
4. Suppression of Ph-cell

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