Chronic Myeloid LeukemiaBy Ganna (Anya) Brych

General Overview

• Also called: -chronic myelogenous leukemia-chronic granulocytic leukemia-chronic myelocytic leukemia.

• mostly affects adults (chance increases in people 65 and older)

• Can develop in children/younger people• Epidemiology= Can not be transmitted • Prognosis = live good-quality lives with medication

Symptoms

• Some don’t have symptoms in first stages

Possible symptoms:

-Leukopenia (shortage of normal white blood cells) -Neutropenia (low levels of normal neutrophils)-Thrombocytopenia (shortage of blood platelets)-Bleeding and bruising -Anemia-Shortness of breath

Symptoms (cont.)

Possible symptoms (cont.) :-Feeling of fullness in the abdomen-Fever -Enlarged lymph nodes -Night sweats-Weight loss -Loss of appetite-Recurrent infections

Diagnosis• Blood Tests- a complete blood count (CBC)

- lower-than-normal red cell count - abnormal number of platelets (either too high or too

low)- High white cell count

- a blood cell examination (test for leukemic blast cells and marrow cells)- high proportion of white cells

Diagnosis (cont.)

• Bone Marrow Tests - bone marrow aspiration (remove a liquid marrow sample) - bone marrow biopsy (remove a small amount of bone marrow)• measure the number/structure of chromosomes • determine any chromosome abnormality (Ph

chromosome)• confirm blood test findings

Diagnosis (cont.)• Hematopathologist confirms the diagnosis + identifies the phase

• Looks for: -presence of the Philadelphia chromosome-number of cells with the Bcr-Abl oncogene

Can Perform: • Cytogenetic analysis - identifies certain changes in chromosomes

and genes by use of a karyotype • Fluorescence in situ hybridization (FISH) - detects Bcr-Abl using

fluorescent dyes• Polymerase chain reaction (PCR) - identify and measure Bcr-Abl

oncogenes not found by “FISH”

Causes• Risk factors

-exposure to very high doses of radiation -high-dose radiation therapy (radiotherapy)

• Abnormal chromosome (Philadelphia or Ph chromosome) = translocation between chromosomes 22 and 9

• Causes development of cancer-causing gene (oncogene) Bcr-Abl

Development

• oncogene causes production of mutated protein called Bcr-Abl tyrosine kinase by stem cells

• starts with a mutation to a single stem cell (in the bone marrow)

• Stem cells form blood cells • multiplies into many cells • The CML cells grow and survive better than

normal cells• Uncontrolled growth of CML cells = cancerous

Phases• Each phase determined by the number of

blast cells• Severity of symptoms increases

• 3 Phases -Chronic Phase CML-Accelerated Phase CML-Blast Crisis Phase CML

Chronic Phase CML

• symptoms are mild or not noticeable. • white cells can still fight infection. • long-term drug therapy can control chronic

phase • return to normal activities after treatment

begins.

Accelerated Phase CML

• Low of red cells, • low number of platelets• an increase or decrease in white cells• a high number of blast cells• Symptoms may appear:

-swollen spleen-stomach discomfort

Blast Crisis Phase CML

• increased number of blast cells in marrow and blood

• low red cell and platelet counts• Symptoms :

-infection-bleeding-a lack of energy or feelings of tiredness-shortness of breath-stomach pain (from an enlarged spleen)-bone pain

• effects similar to those caused by an acute leukemia

Treatment

• 2001 FDA approved tyrosine kinase inhibitor drugs (most commonly used today)

• Dose depends on the phase of CML• TKI drug therapy doesn't cure chronic phase

CML -> stable remission• Regular blood and marrow tests to check

progress of treatment

Chronic Phase Treatment • Tyrosine kinase inhibitor (TKI) drugs

-imatinib mesylate (Gleevec®) -dasatinib (Sprycel®)

-nilotinib (Tasigna®)• If Initial Therapy Fails

-interferon alpha (Roferon®-A and Intron® A)

-pegylated interferon alpha-hydroxyurea (Hydrea®)-cytarabine (Cytosar-U®)-busulfan (Myleran®)

** harsher side effects **

Accelerated Phase and Blast Crisis Phase Treatment

• Tyrosine kinase inhibitor (TKI) drugs -imatinib mesylate (Gleevec®)

-dasatinib (Sprycel®) -nilotinib (Tasigna®)

• If Initial Therapy Fails-interferon-busulfan (Myleran®)-cytarabine (Cytosar-U®) -hydroxyurea (Hydrea®)

• Leukapheresis (removal of white blood cells)• Stem cell transplant

Bibliography • "BCR Rearrangement–Negative Chronic Myelogenous Leukemia Revisited."

Journal of Clinical Oncology. American Society of Clinical Oncology, n.d. Web. 15 Mar. 2014. <http://jco.ascopubs.org/content/19/11/2915/F3.expansion>.

• "Chronic Myeloid Leukemia (CML)." Learn About Cancer. American Cancer Society, n.d. Web. 15 Mar. 2014.

• "Chronic Myeloid Leukemia." MedlinePlus. U.S. National Library of Medicine, n.d. Web. 15 Mar. 2014. <http://www.nlm.nih.gov/medlineplus/chronicmyeloidleukemia.html>.<http://www.cancer.org/cancer/leukemia- chronicmyeloidcml/index>.

• "Chronic Myelogenous Leukemia." Leukemias. Memorial Sloan Kettering Cancer Center, n.d. Web. 15 Mar. 2014. <http://www.mskcc.org/cancer-care/adult/chronic-myelogenous- leukemia>.

• Shah, Neil P. "Chronic Myeloid Leukemia." Disease Information and Support. The Leukemia and Lymphoma Society, n.d. Web. 15 Mar. 2014. <http://www.lls.org/#/diseaseinformation/leukemia/chronicmyeloidleukemia/>.