Battling Leukemia: Methods of Diagnosis Expected to Improve

Article excerpt

Leukemia is a cancer of the white blood cells (WBCs). It results from an uncontrolled proliferation of a clone of abnormal cells. "Over the past 100 years, our understanding of leukemia has evolved that we now recognize it to be a disease of the hematopoietic stem cell," says Ian Chin Yee, MD, FRCPC, chief/chair of hematology, associate professor of medicine, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada.

All humans have a tiny population of hematopoietic stem cells that function to generate all the normal cellular constituents of blood, including the red blood cell, WBC and platelets. By definition, stem cells have the capacity to self renew and generate multiple other cell lineages. It is believed that leukemia arises when a genetic alteration occurs in the hematopoietic stem cell or very early progenitor cell, Dr. Yee explains. These genetic mutations can occur spontaneously or as a result of viruses, toxic chemicals or radiation. A mutated stem cell becomes leukemic if its growth is uncontrolled. Furthermore, leukemic cells expand at the expense of other normal bone marrow elements, eventually resulting in bone marrow failure and causing anemia, neutropenia and thrombocytopenia.

Leukemia is generally divided into two broad categories--acute leukemia and chronic leukemia. As the term implies, Dr. Yee says acute leukemia describes the very aggressive natural history of this cancer, which usually rapidly progresses over a period of weeks to months and causes death. Chronic leukemias, on the other hand, behave more indolently and usually progress over a period of years.

Leukemias are further subdivided based upon cell type--either lymphoid or myeloid origin. Based on this classification, leukemias can be subdivided into acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphoid leukemia (CLL). As the types of leukemia behave and respond differently to treatments, it is important to distinguish these blood cancers, Dr. Yee says.

Tried and True Tests

Because leukemias are essentially a blood disorder, Wendy Brown, RT, technologist, investigational hematology, London Health Sciences Centre, says the hematology laboratory plays a crucial role in diagnosing and differentiating the subtypes of leukemia. Initially, a complete blood count (CBC) will be run to identify changes in the key parameters affected by leukemia, i.e., the WBCs, hemoglobin and platelet counts.

In CLL, an elevated lymphocyte count detected by a hematology analyzer is often the first indication that a patient may have a disease affecting the blood, Brown says. Similarly, in CML, if a persistent increase in neutrophils exists without the presence of infection, further investigation should be performed to rule out a leukemic process.

In acute leukemias, patients often present a severe illness that results in either bleeding or infection. A CBC may show a dramatic increase in the WBC accompanied with very low hemoglobin and platelets. In a subtype of AML affecting mainly promyeloctes, Brown says patients may also have derangement of their coagulation parameters as detected by the prothrombin time and activated partial thromboplastin time. A reduced fibrinogen with elevated D-Dimer, indicating a process of disseminated intravascular coagulation, may also be seen.

Morphologic examination with a microscope is the first critical step in diagnosing and classifying leukemias. For this reason, Brown says the general duty technologist plays a critical role in the initial identification of an abnormal cell population on a blood film. The hallmark of acute leukemia is the presence of very immature cells, so-called blasts.

In contrast, Brown says chronic leukemias are associated with more mature lymphoid or myeloid cells. Because by definition acute leukemia is a proliferation of very immature blast cells, distinguishing ALL from AML can often be challenging and require further testing. …