Efficacy and toxicity of IFN-alpha2b combined with cytarabine in chronic myelogenous leukaemia.

Newly diagnosed chronic myelogenous leukaemia (CML) patients (n = 65) were treated with interferon (IFN)-alpha2b (5 x 106 IU/d s.c.) combined with monthly courses of cytarabine (20 mg/d s.c. for 14 d). Median age of patients enrolled was 45 years. The endpoints of the study were clinical efficacy and toxicity. The survival rates at 3 years and 5 years were 77% and 56%, respectively. The rate of complete haematological response was 60%. Evaluation of cytogenetic response was available in 29/65 patients. A complete cytogenetic response was seen in 3/29 patients (10%). W.H.O. toxicity grade 3-4 occurred in only 22/523 evaluable treatment cycles. Since the study protocol required intermittent or definitive discontinuation of cytarabine in case of moderate leucopenia (white blood cells (WBC) <5 x 109/l), combined cytopenia (WBC < 5 x 109/l, platelets <100 x 109/l), and isolated moderate thrombocytopenia (<100 x 109/l), the drug had to be discontinued temporarily or definitively in 200 cycles and the dose of cytarabine had to be reduced in 35 cycles. Thus, only 25% of the planned dose of cytarabine could be administered. At this dosage it would appear that cytarabine had no effect on survival and did not improve remission rates. We conclude that a clinical benefit for the addition of cytarabine to the treatment of CML with IFN might only be achieved by the administration of a higher cumulative dose of cytarabine, suggesting that lower leucocyte counts of 2-4 x 109/l have to be tolerated.

[Chronic idiopathic thrombocytopenic purpura. Current therapy concept and introduction to pathophysiologic, clinical and diagnostic aspects]. / Die chronische idiopathische thrombozytopenische Purpura. Aktuelles Therapiekonzept und Einführung in Pathophysiologie, Klinik und Diagnostik.

PATHOPHYSIOLOGY: Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by platelet destruction due to an antiplatelet autoantibody, usually of the IgG class, which coats autologue platelets and leads to their elimination by the reticuloendothelial system (RES). While in childhood ITP is more usually an acute and self-limiting problem which needs no drug treatment, adult ITP is a relatively common chronic hematological disease. TREATMENT: Treatment aimes at inhibition of antibody-production and binding on thrombocytes and thrombocyte phagocytosis by the RES. Therapy should result in a platelet count of > 100,000/microliter or at least in stabilization of the platelet count without bleeding. Therapeutic approaches were divided into emergency and long-term treatment. In patients who require non-emergency treatment conventional-dose corticoids (1 to 2 mg/kg/d prednisone) are recommended as initial treatment, whereas pulsed high-dose dexamethason is recently reported to be effective in refractory ITP. After unsuccessful splenectomy or if treatment with gammaglobulins fails alternative and partly experimental therapies may have to be used. CONCLUSION: Treatment of adult ITP includes established medical, immunological and surgical measurements. Their application depends on diseases progression as well as imminent or manifest complications. Remission is achieved in up to 75% of all patients. Alternative treatments remain for refractory cases.

[Oligosymptomatic sprue--report of 4 cases]. / Oligosymptomatische Sprue--ein Bericht über 4 Fälle.

In the last 5 years we observed four cases of oligosymptomatic celiac disease. All patients presented isolated manifestations of malabsorption, but we did not find the typical symptoms of celiac disease, like diarrhea or steatorrhea. Three patients showed an iron deficiency anemia refractory to therapy and one patient a distinct osteomalacia with spontaneous bone fractures. In all these cases we were able to point out the typical microscopic feature and tissue antibodies of the celiac disease. Treating the patients with a gluten-free diet, the symptoms disappeared. These observations demonstrate the importance of the small bowel biopsy in cases of causative unknown isolated manifestations of malabsorption, which possibly belong to the celiac disease.

MACOP-B chemotherapy for the treatment of high grade and intermediate grade non Hodgkin's lymphoma.

Between Nov. 1985 and Nov. 1988, sixty-three patients with high grade malignant (hg) and intermediate grade malignant (img) Non Hodgkin's Lymphoma (NHL) were treated with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin). Thirty-seven patients received MACOP-B as an upfront treatment modality, whereas twenty-six patients had relapsed disease and received MACOP-B as a salvage protocol. Four weeks after termination of therapy, 75% of patients with de novo NHL and 72% of the patients with relapsed NHL were in complete remission (CR). In the group of newly diagnosed NHL, 22% achieved partial remission (PR) and 3% no change (NC), whereas in the group with relapsed disease 14% had PR and 14% had progressive disease (PD). At a medium follow-up of 12 months (range 1 month to 33 months), 74% of patients with de novo NHL continued to be in CR whereas the continuous CR rate in patients with relapsed disease was 35%. Overall survival after 30 months of observation for the patient group with de novo NHL was 75% and 40% for patients with relapsed NHL. The mean duration for completion of the projected 12 chemotherapy cycles, given in weekly intervals, was 12.9 and 13.5 weeks in upfront or salvage therapy, respectively. With low incidence of major toxicities, application of drugs on an outpatient basis, and high efficacy, MACOP-B shows substantial advantages for therapy of de novo and relapsed NHL.