ABSTRACT
PURPOSE: To evaluate the efficacy of the combination, alpha-interferon (IFN)-hydroxyurea (HU) in the treatment of patients with Philadelphia positive chronic myelogenous leukaemia (Ph'-CML). PATIENTS AND METHODS: A prospective study was started in 1988 in which 30 patients with chronic phase, low-risk Ph'-CML, according to Kantarjian's staging system, were included. They were treated with IFN at a dose of 5 MU/m2 subcutaneously twice a week plus HU in doses between 0.5 and 3 g/m2/day. The clinic and biologic controls performed twice a month included granulocyte alkaline phosphatase, and cytogenetic studies of bone-marrow and peripheral blood were carry out every third month. The quality and duration of haematologic and cytogenetic remissions were evaluated, along with the untoward effect of the treatment. Survival was estimated in accordance to the Kaplan Meier method. RESULTS: The mean age was 49 years (range: 17-70) and the M/F ratio was 18/12. The median follow-up was 51 months (range: 8-89). Twenty patients were in early- and four late-chronic phase. Complete haematological remission (CHR) was achieved in 26 patients (87%) with a median of 52 months and an estimated global median survival of 81 months. Cytogenetic response was seen in 11 patients (52%) of the 21 who were evaluable after 11 months of treatment. Disappearance of Ph' (complete cytogenetic response) was seen in 6 cases (28%). The incidence of early blast crisis in the first three years was, respectively, 0%, 3% and 6%. The treatment toxicity was negligible in most cases, having to suppress the treatment only in one patient due to persistent fever. CONCLUSIONS: The association of IFN and HU is effective and well tolerated in patients with low-risk CML, and it improves survival in CHR and overall survival.
Subject(s)
Hydroxyurea/therapeutic use , Immunologic Factors/therapeutic use , Interferon-alpha/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Leukemia, Myeloid, Chronic-Phase/therapy , Adolescent , Adult , Aged , Combined Modality Therapy , Female , Fever/chemically induced , Humans , Hydroxyurea/adverse effects , Immunologic Factors/adverse effects , Interferon-alpha/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myeloid, Chronic-Phase/drug therapy , Leukemia, Myeloid, Chronic-Phase/mortality , Male , Middle Aged , Prospective Studies , Remission InductionABSTRACT
Serum copper levels (SCL) which are concomitantly related to red blood cell free copper are significantly increased in some malignant lymphomas in the phase of activity. This results in a profound inhibition of red cell key glycolytic enzymes, hexokinase (Hx) being the most sensitive. Fifteen patients (eight with Hodgkin's disease and seven with non-Hodgkin's lymphoma) were studied for serum and red cell copper concentrations and Hx activity. The mean red cell life span was determined using 51Cr labelled red cells. The resulting data shows that in active disease an increase in SCL was associated with a decrease in Hx activity and a shortened red cell survival. In these cases there was no evidence of autoimmune phenomena or of direct bone marrow involvement by the disease. It is suggested that the increase in copper levels results in a shortened red cell life span through a copper-induced inhibition of red cell Hx.
