Chronic Granulocytic Leukemia

Chronic granulocytic leukemia represents about 20 percent of all blood cancers and characteristically occurs in people aged forty to sixty. The onset of the disease is slow and insidious, with the patient generally coming to the conclusion that something is truly wrong after about three to six months. Enlargement of the liver, spleen, and lymph nodes occurs in over half of patients. Laboratory studies show a white blood cell count ten to twenty times normal. These white cells and those in the bone marrow are more mature in appearance than they are in the acute leukemias. Anemia and bleeding problems are frequent, as is a curious increase in the level of vitamin B12.
Enzyme and chromosomal studies are important in the diagnosis of chronic granulocytic leukemia.

These testing methods are used to follow the progress of the disease and the response to chemotherapy. The so-called "Philadelphia" chromosome, the first abnormal chromosome found in the leukemias, occurs in over 90 percent of patients with this disease. Intensive therapy can reduce the number of white cells that display the Philadelphia chromosome, and successful reduction is closely correlated with the duration and completeness of remission.

Without treatment, chronic granulocytic leukemia pursues a slow course with progressive anemia, bleeding, enlargement of organs, and infection. Treatment is based completely on chemotherapy, involving four drugs busulfan, cyclophosphamide, L-PAM, and hydroxurea, each used as a single agent. Although these drugs are relatively ineffective in the acute leukemias, they can induce a complete remission in 90 percent of chronic granulocytic patients. They exert their beneficial action without many of the troublesome effects that accompany multidrug therapy.

Complete remission usually lasts two to four years, after which the disease accelerates and increases in severity. The white cell count mounts, and more immature-looking cells are found displaying chromosomal abnormalities. Clinical signs cannot predict when the disease will enter the accelerated stage. The patient will initially feel worse, lose weight, and have fever, but not so remarkably as to signal the onset of the new phase clearly. A "blast crisis" may occur, with high numbers of circulating immature white blood cells. More intensive therapy using several anti-cancer drugs in combination can induce a remission for another three to six months, but no treatment is satisfactory for this stage of disease. Irradiation of the bone marrow and surgical removal of the enlarged spleen have not improved results. Bone marrow transplantation has been unsuccessful, except in the rare cases when an identical twin was available as a completely compatible donor. Newer techniques of chemotherapy and possibly monoclonal antibodies could offer an improved prognosis in the future.