Chronic myeloid leukemia

Other Names

Chronic granulocytic leukemia; Chronic myelogenous leukemia; CML; Leukemia, chronic myeloid

Overview

(KRAH-nik MY-eh-loyd loo-KEE-mee-uh)An indolent (slow-growing) cancer in which too many Myeloblasts are found in the blood and bone marrow. Myeloblasts are a type of immature blood cell that makes white blood cells called myeloid cells. Chronic myeloid leukemia may get worse over time as the number of Myeloblasts increases in the blood and bone marrow.

Definition

Chronic myeloid leukaemia (CML) is the most common myeloproliferative disorder accounting for 15-20% of all leukaemia cases.

Diagram showing the cells CML can develop from

Epidemiology

Its annual incidence has been estimated at between 1 and 1.5 cases per 100,000 and its prevalence at around 1 in 17,000.

Clinical description

The disease is typically triphasic with a chronic phase (CML-CP), accelerated phase (CML-AP) and blast phase (CML-BP). The majority of patients are diagnosed in the chronic phase and may be either asymptomatic (diagnosed through a routine white blood cell count) or present with fatigue, anaemia, weight loss, night sweats or splenomegaly.

Etiology

Diagram showing the translocation found in the Philadelphia chromosome

CML is characterised by the presence of the Philadelphia chromosome, an abnormality resulting from a balanced translocation between chromosomes 9 and 22 (t(9;22)(q34;q11.2)). This translocation generates a BCR/ABL gene fusion encoding a constitutively active tyrosine kinase.

Inheritance

CML does not appear to be an inherited disease and the factors leading to predisposition for the disorder remain largely unknown.

Symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 100% of people have these symptoms

• Myeloproliferative disorder

30%-79% of people have these symptoms

• Abnormal basophil morphology
• Fatigue(Tired)
• Fever
• Leukocytosis(Elevated white blood count)
• Poor appetite(Decreased appetite)
• Splenomegaly(Increased spleen size)
• Thrombocytopenia(Low platelet count)
• Thrombocytosis(Increased number of platelets in blood)

Management and treatment

Although an allogeneic bone marrow transplant is viewed as the only curative treatment option, the prognosis for patients improved dramatically with the targeted development of imatinib mesylate. Imatinib mesylate is a competitive inhibitor of BCR/ABL tyrosine kinase activity and has held EU marketing authorisation as an Orphan drug for the treatment of CML since 2001.

Diagnosis

Chronic myeloid leukemia in a 4 years old female. Peripheral blood (MGG stain)

Peripheral blood (MGG stain): marked leukocytosis with granulocyte left shift

CML is often suspected on the basis of a complete blood count, which shows increased granulocytes of all types, typically including mature myeloid cells. Basophils and eosinophils are almost universally increased; this feature may help differentiate CML from a leukemoid reaction.

Bone marrow biopsy

A bone marrow biopsy is often performed as part of the evaluation for CML

Cytogenetics

This abnormality can be detected by routine cytogenetics, and the involved genes BCR-ABL1 can be detected by fluorescent in situ hybridization, as well as by PCR.

Treatment

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Bosutinib (Brand name: Bosulif) Treatment of adult patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelougenous leukemia. Also for treatment of adult patients with chronic, accelerated or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.
• Imatinib mesylate (Brand name: Gleevec®)treatment of chronic myelogenous leukemia.
• Ponatinib (Brand name: Iclusig)

Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy. Interferon alfa-2a (recombinant) (Brand name: Roferon®-A) Treatment of chronic myelogenous leukemia.

• Dasatinib (Brand name: Sprycel)dasatinib (Sprycel) was approved for the treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase and newly diagnosed Ph+ ALL in combination with chemotherapy. Previously in June 2013, it was approved for treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
• Omacetaxine mepesuccinate (Brand name: Synribo)
• Nilotinib (Brand name: Tasigna) approved for the treatment of pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase and pediatric patients greater than or equal to 1 year of age with chronic phase Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior tyrosine-kinase inhibitor (TKI) therapy. October 2014 approved for treatment of chronic phase (CP) and accelerated phase (AP) Philadelphia chromosome positive chronic myelogenous leukemia (CML) in adult patients resistant to or intolerant to prior therapy that included Gleevec(imatinib)

CML glossary

• Acute phase (blast crisis): a phase of cml where there's rapid growth of leukemia cells, resembling acute leukemia.
• Accelerated phase chronic myelogenous leukemia: a phase between the chronic and blastic phases of cml, characterized by increased growth of leukemia cells.
• Allogeneic stem cell transplant: a treatment for cml involving stem cells from a donor given to the patient after high-dose chemotherapy or radiation.
• Autologous stem cell transplant: a procedure using the patient's own stem cells, which are removed, stored, and then returned after intensive treatment.
• Blast cells: immature blood cells. An increase in these cells is seen in cml.
• Blastic phase chronic myelogenous leukemia: the aggressive stage of cml with a high percentage of blast cells.
• Bcr-abl gene: a fusion gene from a chromosome mutation in cml, producing a protein promoting leukemia cell growth.
• Bone marrow aspiration: a procedure where a small amount of bone marrow, usually from the hip, is examined.
• Bone marrow biopsy: a diagnostic procedure examining a small piece of bone and bone marrow.
• Chronic eosinophilic leukemia: a rare form of leukemia marked by high levels of eosinophils.
• Chronic myelogenous leukemia: a type of cancer that starts in blood-forming cells of the bone marrow and invades the blood.
• Chronic myelomonocytic leukemia: a type of leukemia characterized by both an increase in monocytes and granulocytes.
• Chronic neutrophilic leukemia: a rare type of leukemia characterized by a high number of neutrophils in the blood.
• Chronic phase chronic myelogenous leukemia: the initial phase of cml marked by fewer blast cells compared to the advanced phases.
• Chromosomes: structures in cells containing genetic information. The Philadelphia chromosome is linked with cml.
• Clonal hypereosinophilia: a condition characterized by an increase in eosinophils in the blood due to a genetic mutation.
• Cytogenetics: the study of chromosomes and their abnormalities.
• Hematologist: a doctor specializing in blood disorders.
• Hydroxyurea: a drug treating cml, primarily to lower high white blood cell counts.
• Imatinib (gleevec): a targeted therapy drug for cml treatment.
• Interferon-alpha: immunotherapy previously used as a primary cml treatment.
• Juvenile myelomonocytic leukemia: a rare form of leukemia affecting young children, characterized by the overproduction of monocytes.
• Leukapheresis: a procedure lowering very high white blood cell counts by removing the cells from the blood.
• Philadelphia chromosome: an abnormal chromosome found in cml due to a fusion between chromosomes 9 and 22.
• Stem cells: cells in the bone marrow that produce all types of blood cells.
• Tyrosine kinase inhibitors (tkis): drugs that block proteins, slowing leukemia cell growth, e.G., imatinib, dasatinib, and nilotinib.

NIH genetic and rare disease info

• NIH info on Chronic myeloid leukemia

Chronic myeloid leukemia is a rare disease.

Chronic myeloid leukemia Resources
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