Intensive combination chemotherapy and autologous bone marrow transplantation leads to the reappearance of Philadelphia chromosome-negative in chronic myelogenous leukemia

In chronic myelogenous leukemia (CML), the patient enjoys an average of three to four years of fairly normal active life. This chronic phase is followed by the so-called accelerated and blastic phases during which the patient deteriorates rapidly and generally dies of complications, such as internal bleeding or infection. Chemotherapy can induce a second ''chronic'' phase in patients with accelerated disease, but it is short-lived and relapse occurs after three to nine months. CML is characterized by an unusual genetic finding known as the Philadelphia chromosome. Somewhere in the ancestry of some blood cells, pieces of chromosomes 9 and 22 became interchanged. This translocation, as the geneticists call it, is easily observed under the microscope and is called the Philadelphia chromosome. Evidence suggests that abnormal bone marrow cells with the Philadelphia chromosome are capable of suppressing normal cells. However, there is some indication that the suppressed normal cells are not gone, and researchers have now shown that a combination of chemotherapy and autologous bone marrow transplantation can bring out these normal cells in patients with CML. In autologous bone marrow transplantation, some of the patient's own bone marrow is removed and stored during a period of remission following chemotherapy. When the patient relapses after the remission, a very high dose of chemotherapy may be used; the stored bone marrow may then be used to replace the bone marrow destroyed by the chemotherapy. This method was used in the treatment of 15 patients with CML. One patient died of infection during the treatment. Four patients achieved major cytogenetic responses, which means the percent of the cells with the Philadelphia chromosome was reduced to less than 35 percent. Three of these patients suffered relapses after 3, 4, and 12 months. One patient's response has continued for over 15 months. Curiously, of the seven patients who were known to be insensitive to alpha-interferon therapy before the procedure, three became sensitive to alpha-interferon therapy as a result of the autologous bone marrow transplantation. (Consumer Summary produced by Reliance Medical Information, Inc.)