Leukemia, Chronic Granulocytic

Chronic granulocytic leukemia (CGL) is also known as chronic myelogenous (or myelocytic) leukemia. The disease is characterized by the abnormal overgrowth of granulocytic precursors (myeloblasts, promyelocytes, metamyelocytes, and myelocytes) in bone marrow, peripheral blood, and body tissues.

CGL is most common in young and middleaged adults and is slightly more common in men than in women; it's rare in children. In the United States, approximately 3,000 to 4,000 cases of CGL develop annually, accounting for roughly 20% of all leukemias.

The clinical course of CGL proceeds in two distinct phases: the insidious chronic phase, with anemia and bleeding abnormalities and, eventually, the acute phase (blastic crisis), in which myeloblasts, the most primitive granulocytic precursors, proliferate rapidly. This disease is invariably fatal. Average survival time is 3 to 4 years after onset of the chronic phase and 3 to 6 months after onset of the acute phase.

Causes

The disease can occur in adults (usually middle-aged) and children. CML affects 1 to 2 people per 100,000 and accounts for 7% to 20% cases of leukemia. It is usually associated with a chromosome abnormality called the Philadelphia chromosome.

Exposure to ionizing radiation is one possible trigger for this chromosome abnormality. Such exposure could occur from a nuclear disaster or from treatment of a previous cancer, like thyroid cancer or Hodgkin's lymphoma. However, the vast majority of people treated for cancer with radiation do not go on to develop leukemia. It takes many years to develop leukemia from this cause.

Signs and symptoms

The following are the most common symptoms of chronic myelogenous leukemia. However, each individual may experience symptoms differently. Symptoms may include:

• anemia
• bleeding
• bruising
• fever
• persistent weakness
• fatigue
• aches in bones and joints
• swollen lymph nodes

The symptoms of chronic myelogenous leukemia may resemble other blood disorders or medical problems. Always consult your physician for a diagnosis.

Diagnosis

In patients with typical clinical changes, chromosomal analysis of peripheral blood or bone marrow showing Ph 1 and low leukocyte alkaline phosphatase levels confirms CGL. Other relevant laboratory results include:

• White blood cell abnormalities: leukocytosis (leukocyte count ranging from 50,000/µl to as high as 250,000/µl), occasionalleukopenia (leukocyte count < 5,000/µl), neutropenia (neutrophil count < 1 ,500/µl) despite a high leukocyte count, and increased circulating myeloblasts
• hemoglobin: often below 10 g/dl
• hematocrit; low (<30%)
• platelet count: thrombocytosis (> 1 millionl/µl) common
• serum uric acid level: possibly > 8 mg/dl
• bone marrow aspirate or biopsy: hypercellular, characteristically shows bone marrow infiltration by significantly increased number of myeloid elements (a biopsy is done only if aspirate is dry); in the acute phase, myeloblasts predominate.
• computed tomography scan: may identify the organs affected by leukemia.

Treatment

Aggressive chemotherapy has so far failed to produce remission in CGL. Consequently, the goal of treatment in the chronic phase is to control leukocytosis and thrombocytosis. The most commonly used oral agents are busulfan and hydroxyurea. Aspirin is commonly given to prevent stroke if the patient's platelet count is over 1 million/µl.
Ancillary CGL treatments include:

• local splenic radiation or splenectomy to increase platelet count and decrease adverse effects related to splenomegaly
• leukapheresis (selective leukocyte removal) to reduce leukocyte count
• allopurinol to prevent secondary hyperuricemia or colchicine to relieve gout due to elevated serum uric acid levels
• prompt treatment of infections that may result from chemotherapy-induced bone marrow suppression.

During the acute phase of CGL, lymphoblastic or myeloblastic leukemia may develop. Treatment is similar to that for acute lymphoblastic leukemia. Remission, if achieved, is commonly short lived. Bone marrow transplant may produce long asymptomatic periods in the early phase of illness but has been less successful in the accelerated phase. Despite vigorous treatment, CGL usually progresses after onset of the acute phase.

Prevention

Avoid exposure to radiation when possible.