Pocket Drug Guide

The clinical progression of chronic myelogenous leukemia can be divided into the following three phases:

•  Chronic (blasts represent 5% or less of cells in blood and bone marrow).

•  Accelerated (blasts represent 6-30% of cells in blood and bone marrow).

•  Blastic (blasts represent 30% or more of cells in blood and bone marrow).

The chronic phase is characterized by a slow accumulation of granulocytes. This accumulation can be easily controlled, but not cured, with medication (inducing hematologic remission, i.e., normalization of blood cell counts and spleen size). Most patients are diagnosed while still in this phase, which varies in duration depending on the maintenance therapy used. The chronic phase usually lasts three to five years before it evolves into accelerated or blastic-phase disease.

In two-thirds of patients, the disease transforms gradually into the accelerated phase, at which point the leukemia is more difficult to manage and symptoms become more severe (the remaining one-third of patients progress straight to the blastic phase). During the accelerated phase, symptoms are caused by an increase in the number of granulocytes and blasts in the bloodstream. The survival of patients diagnosed in this phase averages 1 — 1.5 years.

The accelerated phase is a poorly defined stage for which no universally accepted definition exists. TABLE. Comparison of Three Classifications for Accelerated-Phase Chronic Myelogenous Leukemia shows three published classifications of accelerated phase. The criteria proposed by researchers from the M.D. Anderson Cancer Center in Houston, Texas, have been used most frequently in the recent studies of imatinib (Novartis’s Gleevec/Glivec), the gold-standard therapy for chronic myelogenous leukemia. The criteria of the International Bone Marrow Transplant Registry (IBMTR) are most frequently used in the bone marrow transplantation literature. The most recent classification, proposed by the World Health Organization (WHO), is not often employed.

After 3-18 months, the accelerated phase progresses to an acute blastic transformation, or “blast crisis.” The WHO recently proposed a change in the definition of the blastic phase; the organization suggested using a blast level in the blood of 20% as the threshold for diagnosis of this stage of disease. However, most of the available literature uses the standard cutoff of a 30% blast level in the blood. Skin or tissue infiltration by blasts also characterizes the blastic phase. Cytogenetic evidence of another Ph-positive clone or clonal evolution is usually present. At the blastic phase, the disease resembles acute leukemia. In the majority of patients, chronic myelogenous leukemia then transforms into a condition resembling acute myelogenous leukemia; in about 25% of patients, the leukemia takes on the appearance of acute lymphocytic leukemia.

TABLE. Comparison of Three Classifications for Accelerated-Phase Chronic Myelogenous Leukemia

^aAs a percentage of cells in blood and bone marrow. NA = Not applicable. WBC = White blood cell.

Whether the blast cells seen in blastic-phase disease are of myeloid or lymphoid lineage is an important distinction because it predicts the likely response to treatment and prognosis; patients with lymphoid blastic-phase disease have a better prognosis. Blastic-phase disease is generally resistant to treatment and is fatal within three to six months.

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