INTENSIVE TREATMENT IN ORDER TO MINIMIZE THE PH-POSITIVE CLONE IN CHRONIC MYELOGENIC LEUKEMIA

Several studies indicate that interferon (IFN) treatment, intensive ch emotherapy and autologous bone marrow transplantation (ABMT) effective ly reduce the Ph-positive clone in Chronic Myelogenic Leukemia (CML). In the present study on patients less-than-or-equal-to 55 years, we ha ve combined these three treatment modalities. The aim of the study was to eliminate or minimize the Ph-positive clone to see whether a statu s of minimal residual or Ph-negative disease could be maintained for a longer period of time. After diagnosis, patients received interferon (IFN-a-2b) and hydroxyurea (HU) to keep the white blood cell (WBC) and platelet count below 2-4 and 100-150 x 10(9)/l, respectively. After s ix months of treatment, Ph-analysis was performed. Patients with Ph-po sitive cells in bone marrow then received 1-3 courses of intensive che motherapy. In patients Ph-negative after two courses, bone marrow was harvested and used for ABMT. After a third course, patients with up to 50% Ph-positive metaphases were accepted for ABMT. As of January 1, 1 993, 97 patients were registered in the study. Six months of IFN+HU re duced the percentage of Ph-positive metaphases in 57% of the patients (7% became Ph-negative). The corresponding figures after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were auto transplanted. Seven have relapsed with Pb-positivity 3-22 months after ABMT, while nine are Ph-negative at 1-32+ months after ABMT (two not yet analyzed). Seventeen patients are alive and well, while one died o ne month after ABMT due to interstitial pneumonia. Of the remaining 79 patients, 32 are in continuous chronic phase, 34 were allotransplante d and 13 have died (three during Daunorubicin Ara-C [DA]) treatment, o ne refusing transfusions, nine in blastic transformation). We conclude that intensive treatment effectively reduces the Ph-positive clone in CML. Bone marrow can remain Ph-negative for 32+ months after ABMT. A long follow-up is needed to see whether this treatment prolongs time t o metamorphosis.