Edit concept Create issue ticket

Chronic Myeloid Leukemia

CML

Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is the most common myeloproliferative disorder.

Chronic Myeloid Leukemia - Symptom Checker

Ad Check possible symptoms of Chronic Myeloid Leukemia now!

Presentation

Most of patients with chronic myelogenous leukemia are diagnosed in the chronic phase and then progress to the accelerated and blast phases in 3 to 5 years.

The diagnosis of chronic myeloid leukemia is based on the histopathologic findings in the peripheral blood and the presence of the Philadelphia chromosome in bone marrow cells [2] [4].

The clinical symptomatology of chronic myelogenous leukemia may be insidious. The disease is often discovered with routine blood work in the chronic phase, when an elevated white blood cell (WBC) count is revealed or when an enlarged spleen is found in a general physical examination.

The symptoms change as the disease progresses from chronic, to accelerated, and finally to blast.

Signs and symptoms in the chronic phase are [2]:

Signs and symptoms of progressive disease [2] [3]:

The manifestations of blast crisis are similar to those of acute leukemia. Treatment is ineffective in this stage, and most patients succumb to the disease once they reach this phase and survival is 3-6 months.

Easy Bruising
  • It can lead to easy bruising or bleeding, with frequent or severe nosebleeds and bleeding gums. Some patients with CML actually have too many platelets (thrombocytosis).[cancer.org]
  • There is a lack of red blood cells, leading to anemia, and platelets, leading to bleeding tendencies and easy bruising. CML epidemiology CML is a relatively uncommon type of cancer.[news-medical.net]
  • Initially asymptomatic, CML progression is insidious, with a nonspecific “benign” stage (malaise, anorexia, weight loss) eventually giving way to accelerated or blast phases with more ominous signs, such as splenomegaly, pallor, easy bruising and bleeding[msdmanuals.com]
  • Thrombocytopenia is a condition when there is a low number of platelets which can cause bleeding and easy bruising with no apparent cause. Low numbers of all three blood cell counts is called pancytopenia.[llscanada.org]
  • Initially, pallor, bleeding, easy bruising, and lymphadenopathy are unusual, but moderate or occasionally extreme splenomegaly is common (60 to 70% of cases). With disease progression, splenomegaly may increase, and pallor and bleeding occur.[merckmanuals.com]
Splenomegaly
  • Three of 4 TKI-treated patients did not reach complete hematologic response due to the persistence of thrombocytosis and/or splenomegaly.[ncbi.nlm.nih.gov]
  • One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly.[ncbi.nlm.nih.gov]
  • Here, we report a case of aCMLin a 5-month baby who presented with massive splenomegaly. The diagnosis was in accordance with the WHO criteria established in 2008.[ncbi.nlm.nih.gov]
  • 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.[orpha.net]
  • Initially, pallor, bleeding, easy bruising, and lymphadenopathy are unusual, but moderate or occasionally extreme splenomegaly is common (60 to 70% of cases). With disease progression, splenomegaly may increase, and pallor and bleeding occur.[merckmanuals.com]
Massive Splenomegaly
  • Here, we report a case of aCMLin a 5-month baby who presented with massive splenomegaly. The diagnosis was in accordance with the WHO criteria established in 2008.[ncbi.nlm.nih.gov]
  • Spleen size roughly correlates with the WBC count and massive splenomegaly corresponds to poor prognosis. Hepatomegaly is also common, but lymphadenopathy is usually not present.[lecturio.com]
Respiratory Distress
  • Rarely, patients may present with symptoms of leukostasis such as confusion, blurred vision, respiratory distress , thrombosis, headache or priapism, with WBC count usually 500,000/mcl.[lecturio.com]
Fever
  • In December 2015, he presented at our hospital with fever and lumbago. A complete blood count revealed a white blood cell count of 30,500/µL with 60% blasts, leading to diagnosis of SBP.[ncbi.nlm.nih.gov]
  • Since November 8, 2017, the patient had recurrent fever, and her platelet count rose to 1422   10/L. Subsequently, the E279K mutation in the BCR-ABL kinase region was detected.[ncbi.nlm.nih.gov]
  • They include: Weakness Fatigue Night sweats Weight loss Fever Bone pain (caused by leukemia cells spreading from the marrow cavity to the surface of the bone or into the joint) An enlarged spleen (felt as a mass under the left side of the ribcage) Pain[cancer.org]
  • […] abdominal pain from splenomegaly Hepatomegaly Signs and symptoms of progressive disease: Bleeding, petechiae, and ecchymoses Bone pain and fever Increasing anemia, thrombocytopenia, basophilia, Rapidly enlarging spleen The manifestations of blast crisis[symptoma.com]
  • Symptoms include fever: night sweats, bone pain and weight loss. When tiredness, fever, and an enlarged spleen occur during the blast phase, it is called blast crisis.[secure.ssa.gov]
Fatigue
  • On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 109 /L and platelet count of 366 109 /L.[ncbi.nlm.nih.gov]
  • 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.[orpha.net]
  • Dasatinib maintained a consistent safety profile; headache (33%), pleural effusion (26%), fatigue (23%), and rash (23%) were the most common treatment-related adverse events after the switch.[ncbi.nlm.nih.gov]
  • They include: Weakness Fatigue Night sweats Weight loss Fever Bone pain (caused by leukemia cells spreading from the marrow cavity to the surface of the bone or into the joint) An enlarged spleen (felt as a mass under the left side of the ribcage) Pain[cancer.org]
  • Complications of chronic of chronic myeloid leukemia may include the following: Fatigue due to anemia (decreased number of red blood cells).[symptoma.com]
Anemia
  • We report a case of a chronic myeloid leukemia patient showing progressive bone marrow fibrosis and anemia during imatinib therapy.[ncbi.nlm.nih.gov]
  • MGUS was diagnosed because of absence of anemia, hypercalcemia, lytic bone lesions, or renal failure. Immune thrombocytopenia (ITP) was also diagnosed in this patient following the detection of antiplatelet autoantibodies.[ncbi.nlm.nih.gov]
  • Anemia is a shortage of red blood cells. It can cause weakness, tiredness, and shortness of breath. Leukopenia is a shortage of normal white blood cells. This shortage increases the risk of infections.[cancer.org]
  • Complications of chronic of chronic myeloid leukemia may include the following: Fatigue due to anemia (decreased number of red blood cells).[symptoma.com]
  • He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission.[ncbi.nlm.nih.gov]
Weight Loss
  • 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.[orpha.net]
  • They include: Weakness Fatigue Night sweats Weight loss Fever Bone pain (caused by leukemia cells spreading from the marrow cavity to the surface of the bone or into the joint) An enlarged spleen (felt as a mass under the left side of the ribcage) Pain[cancer.org]
  • Patients may have fevers, night sweats, weight loss and increasing fatigue. Blast phase – During this phase, the number of blasts in the blood stream grows quickly.[bethematch.org]
  • Initially asymptomatic, CML progression is insidious, with a nonspecific “benign” stage (malaise, anorexia, weight loss) eventually giving way to accelerated or blast phases with more ominous signs, such as splenomegaly, pallor, easy bruising and bleeding[msdmanuals.com]
Weakness
  • However, we were unable to determine the mechanism underlying the dasatinib-associated muscle weakness.[ncbi.nlm.nih.gov]
  • However, dysphagia, hoarseness, and muscle weakness progressively developed over 2 weeks. Nerve conduction studies revealed extensive demyelinating changes.[ncbi.nlm.nih.gov]
  • It can cause weakness, tiredness, and shortness of breath. Leukopenia is a shortage of normal white blood cells. This shortage increases the risk of infections.[cancer.org]
  • Five months after the diagnosis, the patient showed diminished vision, hand tremors, and weakness of lower extremities. Flow cytometric immunophenotyping of cerebrospinal fluid revealed the presence of myeloid blasts.[ncbi.nlm.nih.gov]
  • While the bone marrow transplant was successful, Andy was left exhausted and weak from the procedure. He continued to visit the hospital two or three times a week for anti-rejection drugs and follow-ups.[childrenwithcancer.org.uk]
Abdominal Pain
  • Approximately 5 months after the initiation of nilotinib for CML, he developed upper abdominal distension with intermitting abdominal pain, and based on abdominal computed tomography findings, a diagnosis of pneumatosis intestinalis (PI) was made.[ncbi.nlm.nih.gov]
  • Some patients may also experience extreme fatigue, shortness of breath, and abdominal pain. Blast crisis closely resembles acute leukemia and has a survival range of three to six months.[nationalcmlsociety.org]
  • The symptoms of all types of leukemia are generally the same and include: tiredness and weakness swollen lymph nodes recurrent infections (like bronchitis or tonsillitis ) fever easy bruising bone and joint pain abdominal pain (caused by abnormal blood[kidshealth.org]
  • pain from splenomegaly Hepatomegaly Signs and symptoms of progressive disease: Bleeding, petechiae, and ecchymoses Bone pain and fever Increasing anemia, thrombocytopenia, basophilia, Rapidly enlarging spleen The manifestations of blast crisis are similar[symptoma.com]
Loss of Appetite
  • The lymphoid cells are those white blood cells that help fight viral infections and some bacterial infections Symptoms of CML One of the earliest symptoms of CML includes fatigue, weight loss, loss of appetite, night sweats, anemia, bone pain and easy[news-medical.net]
  • Many affected individuals develop an enlarged spleen (splenomegaly), which can cause a feeling of fullness in the abdomen and a loss of appetite.[ghr.nlm.nih.gov]
  • […] of appetite Unexplained weight loss Pain or aches in your bones or joints Swollen abdomen Headaches Dizziness Vomiting Diagnosing CML If your doctor suspects you may have leukemia, they will want to perform a thorough physical examination and talk with[seattlecca.org]
  • For six months, she had suffered severe and unusual bruising, fatigue, extreme weight loss, eye bleeds, unusual infections, loss of appetite, inability to smell or taste, headaches, enlarged lymph nodes, loss of toenails, and a spleen so enlarged it was[curetoday.com]
Early Satiety
  • On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 109 /L and platelet count of 366 109 /L.[ncbi.nlm.nih.gov]
  • EJ Occasionally, patients with CML have symptoms such as fever, fatigue, sweats, and early satiety due to splenomegaly. However, many patients are asymptomatic at diagnosis.[hematologyandoncology.net]
  • Patients may present with non-specific symptoms of low-grade fever, malaise, night sweats, or abdominal fullness and early satiety due to an enlarged spleen .[lecturio.com]
  • The large spleen may encroach on the stomach and cause early satiety and decreased food intake. Left upper quadrant abdominal pain described as "gripping" may occur from spleen infarction.[emedicine.medscape.com]
  • The most common presenting symptoms are fatigue (usually related to mild to moderate anemia) and modest weight loss (most often due to early satiety from splenomegaly). Fever or bleeding are relatively uncommon.[clinicaladvisor.com]
Abdominal Fullness
  • Symptoms and Signs Patients are often asymptomatic early on, with insidious onset of nonspecific symptoms (eg, fatigue, weakness, anorexia, weight loss, fever, night sweats, a sense of abdominal fullness), which may prompt evaluation.[merckmanuals.com]
  • Splenomegaly, which tends to be present in the blast phase, causes abdominal fullness or discomfort, feeling full early when eating (the spleen is pressing on the stomach), and weight loss.[oncolink.org]
  • Patients may present with non-specific symptoms of low-grade fever, malaise, night sweats, or abdominal fullness and early satiety due to an enlarged spleen .[lecturio.com]
  • Abdominal fullness or abdominal distension. Left upper quadrant pain due to splenic infarction. Signs Splenomegaly - the most common physical finding, which may extend towards the right iliac fossa. Hepatomegaly.[patient.info]
Abdominal Distension
  • Approximately 5 months after the initiation of nilotinib for CML, he developed upper abdominal distension with intermitting abdominal pain, and based on abdominal computed tomography findings, a diagnosis of pneumatosis intestinalis (PI) was made.[ncbi.nlm.nih.gov]
  • Abdominal fullness or abdominal distension. Left upper quadrant pain due to splenic infarction. Signs Splenomegaly - the most common physical finding, which may extend towards the right iliac fossa. Hepatomegaly.[patient.info]
Tachycardia
  • On physical examination, we observed tachycardia, altered mental status, and dehydration. Blood analysis revealed leukocytosis, thrombocytosis, and marked hypercalcemia (18.6 mg/dL).[ncbi.nlm.nih.gov]
Hepatomegaly
  • […] are: Fatigue, weight loss, loss of energy, decreased exercise tolerance Low-grade fever and excessive sweating Elevated white blood cell (WBC) count Splenomegaly Decreased appetite and food intake Left upper quadrant abdominal pain from splenomegaly Hepatomegaly[symptoma.com]
  • Hepatomegaly also occurs, although less commonly than splenomegaly. Hepatomegaly is usually part of the extramedullary hematopoiesis occurring in the spleen.[emedicine.medscape.com]
  • Hepatomegaly is also common, but lymphadenopathy is usually not present. In 25% of cases, patients are asymptomatic and CML is diagnosed on routine blood tests or palpable spleen on physical examination.[lecturio.com]
  • […] sweating from hypermetabolism Elevated white blood cell (WBC) count or splenomegaly on routine assessment Early satiety and decreased food intake from encroachment on stomach by enlarged spleen Left upper quadrant abdominal pain from spleen infarction Hepatomegaly[emedicine.medscape.com]
Hepatosplenomegaly
  • Due to presenting complaint of bleeding diathesis and absence of hepatosplenomegaly, the case was undiagnosed for CML until the patient reported to us.[ncbi.nlm.nih.gov]
  • A 59-year-old female with dry cough, referred to our hospital, exhibited hepatosplenomegaly, high basophil count, and high platelet count at admission without any other known chronic diseases.[ncbi.nlm.nih.gov]
  • Symptoms of CML may include: Upper abdominal pain – hepatosplenomegaly Poor appetite – enlarged spleen may compress the stomach Low-grade fever/night sweats – increased metabolism Gout – increased cell turnover excess purines broken down to uric acid[geekymedics.com]
  • It can also present with symptoms indicative of hepatosplenomegaly and the resulting upper quadrant pain this causes. The enlarged spleen may put pressure on the stomach causing a loss of appetite and resulting weight loss.[en.wikipedia.org]
  • […] that Alfred Velpeau in France be credited with the first detailed description of what must have been leukemia in 1827. 11 As a result of astute clinical observations, he described a 63-year old florist and lemonade salesman who presented with gross hepatosplenomegaly[haematologica.org]
Bone Pain
  • They include: Weakness Fatigue Night sweats Weight loss Fever Bone pain (caused by leukemia cells spreading from the marrow cavity to the surface of the bone or into the joint) An enlarged spleen (felt as a mass under the left side of the ribcage) Pain[cancer.org]
  • Bone pain or joint pain because of expansion of the bone marrow from the buildup of white blood cells. Swollen or enlarged spleen due to the e storage of the extra blood cells in the spleen.[symptoma.com]
  • Symptoms include fever: night sweats, bone pain and weight loss. When tiredness, fever, and an enlarged spleen occur during the blast phase, it is called blast crisis.[secure.ssa.gov]
  • The lymphoid cells are those white blood cells that help fight viral infections and some bacterial infections Symptoms of CML One of the earliest symptoms of CML includes fatigue, weight loss, loss of appetite, night sweats, anemia, bone pain and easy[news-medical.net]
  • Symptoms include those mentioned above, as well as bone pain, infection, acute bruising and bleeding. Bruising and seepage of blood into the skin is a primary feature of this phase.[nationalcmlsociety.org]
Night Sweats
  • On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 109 /L and platelet count of 366 109 /L.[ncbi.nlm.nih.gov]
  • 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.[orpha.net]
  • They include: Weakness Fatigue Night sweats Weight loss Fever Bone pain (caused by leukemia cells spreading from the marrow cavity to the surface of the bone or into the joint) An enlarged spleen (felt as a mass under the left side of the ribcage) Pain[cancer.org]
  • Patients may have fevers, night sweats, weight loss and increasing fatigue. Blast phase – During this phase, the number of blasts in the blood stream grows quickly.[bethematch.org]
  • If you have symptoms, they may include: Fatigue Weight loss Night sweats Fever Pain or a feeling of fullness below the ribs on the left side Tests that examine the blood and bone marrow diagnose CML.[nlm.nih.gov]
Petechiae
  • Other possible symptoms of a blast crisis include: Bruising Excessive sweating (night sweats) Fatigue Fever Pressure under the lower left ribs from a swollen spleen Rash -- small pinpoint red marks on the skin ( petechiae ) Weakness A physical examination[nlm.nih.gov]
  • […] tolerance Low-grade fever and excessive sweating Elevated white blood cell (WBC) count Splenomegaly Decreased appetite and food intake Left upper quadrant abdominal pain from splenomegaly Hepatomegaly Signs and symptoms of progressive disease: Bleeding, petechiae[symptoma.com]
  • In accelerated phase and blast crisis, the patient presents like acute leukemia with fever, bleeding, petechiae, ecchymosis and pallor due to overexpansion of bone marrow with the blast cells and ineffective production of platelets and red blood cells[lecturio.com]
  • In some patients who present in the accelerated, or acute, leukemia phase of the disease (skipping the chronic phase), bleeding, petechiae, and ecchymoses may be the prominent symptoms.[emedicine.medscape.com]
Increased Sweating
  • The symptoms of CML during the condition's chronic or accelerated stage include: tiredness loss of appetite weight loss anaemia(fewer red blood cells) increased sweating abnormal or unusual bruising and bleeding bone pain haedaches and visual disturbances[hse.ie]
Irritability
  • It may first appear as anemia, with the patient finding colds and other minor irritations difficult to control. A complete blood count can rule out other disorders and indicate a need to conduct additional tests to confirm the CML diagnosis.[nationalcmlsociety.org]
  • GLEEVEC is sometimes associated with stomach or intestinal irritation. GLEEVEC should be taken with food and a large glass of water to minimize this problem.[us.gleevec.com]
  • The most common side effects include thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, weakness, skin irritation where the drug was given, fever, and infection. Learn more about the basics of chemotherapy .[cancer.net]
Hand Tremor
  • Five months after the diagnosis, the patient showed diminished vision, hand tremors, and weakness of lower extremities. Flow cytometric immunophenotyping of cerebrospinal fluid revealed the presence of myeloid blasts.[ncbi.nlm.nih.gov]

Workup

The diagnosis of chronic myeloid leukemia is based on the following [2]:

  • Histologic findings in the peripheral blood
  • Philadelphia (Ph) chromosome in bone marrow cells [4]

The workup for chronic myeloid leukemia should include the following [2]:

Complete blood count with differential

  • Total white blood cell count - 20,000-60,000 cells/μL
  • Increased basophils and eosinophils
  • Mild to moderate anemia

Peripheral blood smear [2]

  • Leukocyte alkaline phosphatase - absent in most cells
  • Immature myeloid cells
  • Leukoerythroblastosis, with circulating immature cells

Bone marrow analysis [2] [4]

  • Philadelphia chromosome present - transposition of chromosomal material between chromosomes 9 and 22
  • Elevated cell counts of neutrophils, eosinophils, and basophils
  • Megakaryocytes are prominent and may be increased
  • Mild reticulin fibrosis
Philadelphia Chromosome Positive
  • A case is described in which quantitative polymerase chain reaction failed to detect the presence of BCR-ABL1 fusion transcript in a Philadelphia chromosome-positive chronic myeloid leukemia patient.[ncbi.nlm.nih.gov]
  • We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug.[ncbi.nlm.nih.gov]
  • Patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase (CML-CP; N   112) received nilotinib 300 mg twice daily.[ncbi.nlm.nih.gov]
  • Currently TKI is the main therapy in CML Philadelphia chromosome-positive (Ph-positive) cases.[ncbi.nlm.nih.gov]
  • I’ve Got Information About Ph CML Philadelphia chromosome-positive (Ph ) chronic myeloid leukemia (CML) in chronic phase (CP) may be a disease you’ve never heard of, but remember: you are not alone.[sprycel.com]
Thrombocytosis
  • Three of 4 TKI-treated patients did not reach complete hematologic response due to the persistence of thrombocytosis and/or splenomegaly.[ncbi.nlm.nih.gov]
  • Investigations were suggestive of chronic phase CML (CML-CP) with massive thrombocytosis and magnetic resonance imaging (MRI) of the brain revealed subdural hematoma.[ncbi.nlm.nih.gov]
  • Blood analysis revealed leukocytosis, thrombocytosis, and marked hypercalcemia (18.6 mg/dL). His chest CT scan showed diffuse lytic lesions and bone destruction concerning for diffuse bone marrow involvement.[ncbi.nlm.nih.gov]
  • Some patients with CML actually have too many platelets (thrombocytosis). But those platelets often don't work the way they should, so these people often have problems with bleeding and bruising as well.[cancer.org]
  • Essential Thrombocytosis: The chronic neoplastic proliferation of platelets with platelet counts increasing as high as 2,000,000/mcl. WBCs and red blood cells may or may not increase concomitantly.[lecturio.com]
Karyotype Abnormal
  • The Philadelphia chromosome, which is a diagnostic karyotypic abnormality for chronic myelogenous leukemia, is shown in this picture of the banded chromosomes 9 and 22.[emedicine.medscape.com]
Hemoglobin Decreased
  • Some common side effects that you may experience include: Fluid retention (holding water) Muscle cramps, pain, or bone pain Abdominal pain Anorexia (loss of appetite) Vomiting Diarrhea Decreased hemoglobin (decrease in blood cells which carry oxygen)[us.gleevec.com]
Uric Acid Increased
  • Symptoms of CML may include: Upper abdominal pain – hepatosplenomegaly Poor appetite – enlarged spleen may compress the stomach Low-grade fever/night sweats – increased metabolism Gout – increased cell turnover excess purines broken down to uric acid[geekymedics.com]
Hypercellular Bone Marrow
  • bone marrow biopsy with numerous megakaryocytes Increased reticulin fibers (reticulin stain) Marked hypercellularity Myeloblastic transformation - bone marrow biopsy: Increase in stromal and vascular structures Marked increase in fibroblasts Numerous[pathologyoutlines.com]
  • Because of such abnormal shapes, these cells are destroyed before releasing into the peripheral blood circulation, leading to cytopenias and hypercellular bone marrow.[lecturio.com]

Treatment

The goals of treatment of chronic myeloid leukemia are to achieve hematologic, cytogenetic, and molecular remission. Although a variety of medications have been used in chronic myeloid leukemia, including myelosuppressive agents and interferon alfa, the tyrosine kinase inhibitor, imatinib mesylate, is currently the drug of choice [7].

Other drugs in this category are increasingly used [8]. Some patients with molecular remissions from interferon alfa and imatinib may be cured, but this can only be established over time [3] [5] [9].

Allogeneic bone marrow transplantation is currently the only proven cure for chronic myeloid leukemia [8]. Bone marrow or stem cell transplantation are investigative therapies at present used only for younger patients and are extremely expensive.
New agents that are currently under research may prolong the survival of patients with chronic myeloid leukemia and may even offer the possibility of eventual cure [8] [9].

In October 2012, the US Food and Drug Administration (FDA) approved omacetaxine (Synribo). Omacetaxine is a protein translation inhibitor that is indicated in the accelerated phase of patients with chronic myeloid leukemia resistant to or intolerant to 2 or more tyrosine kinase inhibitors [10].

Leukapheresis, using a cell separator, can lower white blood cell counts rapidly and safely. It is used in patients with white blood cell counts greater than 300,000 cells/µ and can alleviate acute symptoms [8].

Splenectomy and splenic irradiation have been used in patients with large and painful spleens, usually in the later phases of chronic myeloid leukemia [8]. Splenectomy is associated with a high incidence of post-operative complications, morbidity, and mortality.

Prognosis

In the past, patients with chronic myeloid leukemia had a median survival rate of 3-5 years from the time of diagnosis. New therapeutic agents have resulted in improvement in survival.

Currently, patients have a median survival of 5 or more years, 50-60% of patients survive at least 5 years. The improvement has resulted from earlier diagnosis, improved therapy with interferon, bone marrow transplantation, and better supportive care [5].

Some patients with remissions from interferon alfa, may be cured, but this can only be proven over time [5] [6].

Etiology

Chronic myeloid leukemia is caused by a single, specific genetic mutation. More than 90% of cases result from a mutation of a gene responsible for cell production known as the Philadelphia chromosome [3].

Causes for the mutation are not fully known, though exposure to radiation and toxic chemicals is strongly suspected.

Epidemiology

Chronic myeloid leukemia accounts for 20% of all leukemias affecting adults [2]. It usually affects the middle-aged, uncommonly, occurring in younger individuals.

Younger patients may have a more aggressive form of chronic myeloid leukemia, presenting in the accelerated phase or in blast crisis.

Sex distribution
Age distribution

Pathophysiology

Chronic myeloid leukemia is an acquired abnormality that involves the hematopoietic stem cells. It is characterized by an abnormality that causes a reciprocal translocation of the long arms of chromosomes 22 and 9 [1] [3].

The translocation results in a shortened chromosome 22, first noted by Nowell and Hungerford in Philadelphia and named the Philadelphia (Ph1) chromosome after the city where it was discovered [2] [3].

The resulting gene forms a mutant protein with strong tyrosine kinase activity. The manifestation of this protein causes the development of chronic myeloid leukemia through processes that are not yet fully understood [2] [3] [4].

The cause of chronic myeloid leukemia is still unknown, but exposure to ionizing radiation is suspected. It was observed among survivors of the atomic bombing of Hiroshima and Nagasaki. Other agents, such as benzene, are also possible causes [2].

Prevention

There are no guidelines for prevention of chronic myeloid leukemia.

Summary

Chronic myeloid leukemia is a bone marrow stem cell disorder characterized by increased production of the granulocytic white blood cells and decreased hematopoiesis leading to cytopenia.

Chronic myeloid leukemia progresses through 3 phases: chronic, accelerated, and blastic. In the chronic phase of the disease most white blood cells are mature. In the accelerated phase additional cell abnormalities occur. In the blast phase immature cells proliferate rapidly, crowding out normal cells.

Prolonging survival is the primary goal of therapy. Allogeneic stem cell transplantation (SCT) remains the only curative treatment, but is rarely used in elderly patients [1] [2].

Patient Information

What is chronic myeloid leukemia?

Chronic myeloid leukemia is a slowly progressing form of blood cancer. It interferes with the production of blood cells in the bone marrow, where blood cells are made. As a result your body makes too many abnormal, immature white blood cells, called blast cells. Healthy white blood cells help to fight infection. The abnormal cells can no longer perform this function.

In chronic myeloid leukemia the bone marrow makes a greatly increased numbers of abnormal blast cells. These immature cells live longer than normal cells. They crowd out healthy white blood cells, and also red blood cells and platelets (responsible for clotting) as well.

What are the symptoms of chronic myeloid leukemia?

Chronic myeloid leukemia has three phases: chronic, accelerated, and blastic. Chronic-phase chronic myeloid leukemia is the earliest phase and the easiest to treat. The individual may have no symptoms at all.
In the accelerated phase, the number of abnormal blood cells increases. Some or all of these symptoms may be present:

What causes chronic myeloid leukemia?

The exact cause of chronic myeloid leukemia is not known. It starts when a new chromosome, called the Philadelphia chromosome, is formed by the switching of the DNA between two chromosomes (9 and 22).

This new gene tells blood cells to make a new protein which causes the body to begin making too many abnormal, or immature, white blood cells, leaving less room for healthy blood cells and platelets.

Who gets chronic myeloid leukemia?

Anyone can get chronic myeloid leukemia; however, it usually affects middle-aged or older adults. It rarely occurs n children. It happens more frequently in men and those exposed to radiation and certain chemicals.

Family history is not a risk factor. The chromosome mutation that leads to chronic myelogenous leukemia is not passed from parents to their children. This mutation is believed to be acquired, meaning it occurs after birth.

How is chronic myeloid leukemia diagnosed?

Chronic myeloid leukemia is diagnosed using blood tests that show the type and number of the various blood cells, especially white blood cells. Diagnosis is confirmed by biopsy (sampling) of the bone marrow when the presents of a mutated chromosome, called the Philadelphia chromosome, is found.

How is chronic myeloid leukemia treated?

Once a diagnosis of chronic myeloid leukemia is made the goal of treatment is to prevent the progression of the disease as long as possible. Best treatment should include a referral to and evaluation by a doctor with special training in blood diseases/cancers (hematologist-oncologist).

The goal is to stay in the chronic phase and remain symptom-free.
Chronic myelogenous leukemia is a disease that most patients will continue treatment for the rest of their lives.

Treatment of chronic myeloid leukemia is aimed at destroying the abnormal blood cells and restoring normal white blood cells to normal levels.

Diagnosis and treatment beginning in the early, chronic phase of the disease can slow and even prevent the disease from moving to a more serious level.

Medications known as tyrosine kinase inhibitors are usually the first form of treatment. They slow down the production of abnormal white cells.

Other treatment options include chemotherapy, to destroy the abnormal white blood cells, and with interferon which decreases the production of white blood cells. A stem cell transplant from a matching donor may be curative but it is difficult to obtain a match and the procedure is very expensive. It is usually used only when other treatments have failed.

What are the complications of chronic myeloid leukemia?

Complications of chronic of chronic myeloid leukemia may include the following:

  • Fatigue due to anemia (decreased number of red blood cells).
  • Excessive bleeding and bruising because the number of platelets (blood cells that help control clotting) is decreased.
  • Bone pain or joint pain because of expansion of the bone marrow from the buildup of white blood cells.
  • Swollen or enlarged spleen due to the e storage of the extra blood cells in the spleen.
  • Infection is a significant risk because abnormal white blood cells are not able to fight off infection.
  • Death will occur if chronic myeloid leukemia cannot be successfully treated.

References

Article

  1. Fenaux P, Gattermann N, Seymour JF, Hellström-Lindberg E, Mufti GJ, Duehrsen U, Gore SD, Ramos F, Beyne-Rauzy O, List A, McKenzie D, Backstrom J, Beach CL. Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-C. British Journal of Haematology 2010, 149: 244–249.
  2. Kantarjian HM, Talpaz M. Chronic myelogenous leukemia. Hematol Oncol Clin N Am. Jun 2004;18(3):XV-XVI.
  3. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. Apr 5 2001;344(14):1038-42.
  4. Kantarjian H, Sawyers C, Hochhaus A, et al, for the International STI571 chronic myeloid leukemia Study Group. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. Feb 28 2002;346(9):645-52
  5. Gambacorti-Passerini C, Antolini L, Mahon FX, Guilhot F, Deininger M al et. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J Natl Cancer Inst. Apr 6 2011;103(7):553-61.
  6. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. Apr 5 2001;344(14):1038-42.
  7. Simonsson B, Gedde-Dahl T, Markevarn B, et al. Combination of pegylated IFN-a2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood. Sep 22 2011;118(12):3228-35.
  8. Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options. Blood. Oct 1 2001;98(7):2039-42.
  9. Cortes JE, Jones D, O'Brien S, Jabbour E, Ravandi F, Koller C, et al. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol. Jan 20 2010;28(3):398-404.
  10. Orr, S. J., Boutz, D. R., Wang, R., Chronis, C., Lea, N. C., Thayaparan, T., Hamilton, E., Milewicz, H., Blanc, E., Mufti, G. J., Marcotte, E. M. and Thomas, N. S. B. (2012), Proteomic and protein interaction network analysis of human T lymphocytes during cell-cycle entry. Molecular Systems Biology, 8: n/a.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2018-06-21 23:06