[Recombinant hematopoietic growth factors in the treatment of various hematologic diseases].
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Biomedical subjects
Publications and source records attributed to S Pawelski.
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In 6 women aged 38 to 68 years with thrombocythaemia during chronic myeloid leukaemia (4 cases), myelofibrosis (1 case), and idiopathic thrombocythaemia (1 case) the effects of recombinant human alpha-interferon (Intron A, rh IFN alpha -2b, Schering) were studied. The drug was given to all patients subcutaneously in one daily dose of 3 x 10(6) u, every day for 3 weeks, and then in the same doses twice weekly for 2 weeks (5 cases) and for 14 weeks (1 case). Intron A caused in all cases a fall of peripheral blood platelet count by 37% to 65.5% (mean 50%) in relation to the initial count (532 - 1,453 x 10(9)/l). The fall of the platelet count occurred usually after 7-10 days of this treatment, and the lowest count was noted usually after 24 days (10 to 42 days). During the treatment in 4 cases the peripheral leucocyte count dropped as well by 20-70%. In no cases exacerbation of chronic myeloid leukaemia was noted, and in the patient with myelofibrosis the enlarged spleen shrunk somewhat. These results of treatment and follow-up of patients with thrombocythaemia treated with Intron A indicate a significant although short-lasting effect of platelet count fall limited, however, to the time of the treatment. Side effects of the drug included mainly febrile conditions, myalgia and arthralgia.
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Low dose Ara-C (10-15 mg/m2) was administered subcutaneously in 1-5 courses of 14 to 21 days to 16 patients with acute nonlymphoblastic leukaemia, mostly in elderly persons and/or with pancytopenia in whom conventional chemotherapy was contraindicated or ineffective. 18 of the 26 patients were females and 8 males. The mean age was 54.9 years ranging from 31 to 81 years. Mean duration of treatment was 15.2 days. Five complete remissions and three partial remissions were obtained. The mean duration of complete remission was 4.7 months and the mean duration of partial remission was 6.7 months. Aggravation of cytopenia during the treatment and hypocellularity of bone marrow aspirates at the end of therapy suggest that low dose Ara-C exerts its main activity by suppression of leukaemic proliferation rather than by induction of differentiation in malignant cells. Our results show that low dose of Ara-C could be valuable alternative treatment in patients with contraindications or ineffectiveness of conventional intensive chemotherapy.
8 patients with severe and 4 with non-severe aplastic anaemia, aged 7 to 46 years, whose suppressor lymphocyte activity was in most cases elevated and who had no histocompatible sibling donor, underwent 1-2 courses of ALG/ATG treatment. 6 patients got CR and 1 PR and during 1-4 years they live with sustaining haemopoiesis, independent of blood transfusion (except one in PR). Among these seven responders increased suppressor lymphocyte activity normalized in 6. The adverse effects of the treatment were granulocyto- and thrombocytopenia, subfebrile states, hepatotoxicity, serum sickness and skin allergy. Five patients died because of early or late complications of the treatment or it's failure. Our results, similar to other authors', are like after BMT and supports the immunological mechanism of A.A. Immunosuppressive treatment with ALG/ATG has many advantages: no need to have identical bone marrow donor, no GVHD, possibility of treatment of patients over 30, even pretreated with blood transfusions, and finally much lower costs and efforts.
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Two groups of AML patients (n1 = 63, n2 = 20) and two groups of ALL patients (n1 = 33, n2 = 15) were treated using polychemotherapy protocols which in each leukaemia subtype differed mainly in adriblastin administration being either in bolus form (30 mg/m2/day i.v.) or fractional form at the beginning 20 mg i.v., then 6 mg/m2 every 6 h. The fractional method of administration was elaborated on experimental data indicating the superiority of continuous infusion of anthracyclines. In AML additional ara-C was given in continuous infusion only on 1 to 3 days, on 4 to 8 days duplicated dose was administered subcutaneously (i.e. 100 mg/m2 every 12 h). In patients given fractional doses of adriblastin and in AML also ara-C in the modified way the statistical analysis revealed a higher CR (ALL - 67%/93%, AML - 46%/60%) and CR + PR rates, a lower rate of infections as the cause of death in the AML group, lower rates of nausea and vomiting as well a lower increase of infections in the course of the induction treatment in the AML group. Another advantage was a lower total dose of adriblastin for remission induction treatment as well as an elevated cumulative dose which allows anthracyclines to be longer used. The efficacy of the modified ara-C administration confirms our earlier observation.
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In a group of 280 patients with chronic lymphatic leukaemia, a coexistence of malignant tumours diagnosed simultaneously with the leukaemia was found in 14 cases or 5.0%. No significant difference was observed between the development of the second malignant neoplasm in the patients studied and the expected incidence in the general population, taking into account also the sex and age of patients and their place of residence. No statistically significant relation was found between the duration of CLL and the occurrence of second malignancies. No significant correlation was found between the total dose of cytostatic drugs, corticosteroids or radiotherapy and the incidence of cancer.
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