In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were randomized to receive hydroxyurea or busulfan. Of these, 90.7% were Philadelphia positive; 25.7% were low, 38.2% intermediate, and 36.2% high risk patients according to Sokal's score. The median survival of the busulfan treated Philadelphia-positive patients is 45.4 months and of the hydroxyurea group 58.2 months (P = .008). The survival advantage for the hydroxyurea treated patients is recognized in all risk groups. Sixty four patients reached therapy resistance before blast crisis and were crossed over to the alternative drug. The 23 patients with primary hydroxyurea had a median survival of 5.6 years, the 41 patients with primary busulfan therapy a median survival of 2.7 years (P = .02). Adverse reactions were less frequent with hydroxyurea with no severe adverse effects (lung fibrosis, long lasting bone marrow aplasia). The analysis of white blood cell counts in the course of treatment showed lower counts in the hydroxyurea patients. We conclude that hydroxyurea is superior to busulfan in therapy of CML in chronic phase and should be used as first line therapy. Busulfan may have a role as secondary therapy after hydroxyurea resistance or intolerance.

Summary.In an attempt to evaluate the role of thrombopoietin (TPO) in the pathobiology of aplastic anaemia (AA), we have examined TPO levels in sera from 54 AA patients and 119 healthy controls. A total of 92 samples were collected from AA patients: 43 samples were harvested at diagnosis, 23 samples in the cytopenic period after treatment, and 26 samples when patients were in partial (n ¼ 10) or complete remission (n ¼ 16) following immunosuppressive treatment. TPO serum levels were assessed by a sandwich-antibody ELISA that utilized a polyclonal rabbit antiserum for both capture and signal. Serum samples from normal donors revealed a mean TPO level of 95·3 Ϯ 54·0 pg/ ml (standard deviation). Mean TPO levels in AA sera collected at diagnosis and before onset of treatment were 2728 Ϯ 1074 pg/ml (P < 0·001 compared to normal controls; mean platelet count at that time: 27 × 10 9 /l). TPO serum levels of AA patients in partial or complete remission after immunosuppressive treatment were significantly lower than TPO levels at diagnosis (P < 0·001). However, despite normal platelet counts (mean 167 × 10 9 /l), TPO levels remained significantly elevated in complete remission (mean TPO 1009 Ϯ 590 pg/ml, P < 0·001 compared to normal controls). There was a significant inverse correlation between serum TPO levels and platelet counts in AA patients who were not transfused for at least 2 weeks prior to sample collection (coefficient of correlation (r) ¼ ¹0·70, P < 0·0001).In summary, TPO levels were highly elevated in sera of patients with AA. Thus there is no evidence to suggest an impaired TPO response contributing to thrombocytopenia in AA. Thrombopoietin did not return to normal levels in remission, indicating a persisting haemopoietic defect in remission of AA. We hypothesize that elevated levels of TPO may be required to maintain normal or near normal platelet counts in remission of AA.

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During the past decades sickle cell disease and the thalassemias have come to Northern Europe with migrants from the Mediterranean area and Sub-saharan Africa. There are relatively few sickle cell patients in Germany, Switzerland and Austria compared to our neighbors who had colonies in Africa and most physicians do not treat more than 1-2 patients. Due to progress in prophylaxis and therapy, 85 - 90% of children with sickle cell disease in the USA and Europe reach adult age. With increasing age patients suffer chronic organ damage in addition to episodes of acute organ failure which predominate in childhood. Taking care of sickle cell patients is a challenge and requires a large amount of knowledge and experience. In order to give optimal treatment to our patients we need to make use of the experience and study results of colleagues abroad. In this paper the most important clinical manifestations of the disease are discussed and available information sites are presented.