Summary. Myelofibrosis with myeloid metaplasia (MMM) isan uncommon disorder in young individuals, for whom haemopoietic stem cell transplantation offers the only possibility of cure. However, although the latter procedure is associated with significant morbidity and mortality, the clinical course of MMM is variable, with some patients surviving for less than a year and others showing an indolent course. Selection of young MMM patients for transplantation or other newer therapies is currently difficult since no prognostic data exists for this subgroup. In the present collaborative study a number of initial clinical and laboratory parameters have been evaluated for prognosis in 121 MMM patients aged 55 years or less. Median survival of the series was 128 months (95% CI 90-172). In the Cox proportional hazard regression model three initial variables were independently associated with shorter survival: Hb <10 g/dl (P < 0·0001), the presence of constitutional symptoms (fever, sweats, weight loss) (P ¼ 0·001), and circulating blasts у 1% (P ¼ 0·003). Based on the above three criteria, of the 116 patients with complete data, two groups were identified: a 'low-risk' group, characterized by 88 patients with up to one adverse prognostic factor, in whom MMM had an indolent course (median survival 176 months, 95% CI 130-188), and a 'high-risk' group, including 28 patients with two or three factors, who had a more aggressive disease (median survival 33 months, 95% CI 20-42). The above prognostic scoring system showed a high positive predictive value, sensitivity and specificity to predict survival in the series, and could be of help in making treatment decisions in young patients with MMM.

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Summary. Congenital anaemias due to ineffective erythropoiesis may be associated with excessive iron absorption and progressive iron loading. We investigated whether the soluble transferrin receptor (TfR) level was related to the degree of iron overload in 20 patients with thalassaemia intermedia, six patients with congenital dyserythropoietic anaemia type II (CDA II) and four patients with X-linked congenital sideroblastic anaemia (XLSA). All but two patients had increased serum ferritin levels (median 601 mg/l, range 105±2855 mg/l). Multiple regression analysis showed that 62% (P < 0´0001) of the variation in serum ferritin was explained by age and by changes in soluble TfR.Keywords: anaemia, erythropoiesis, erythropoietin, iron overload, soluble transferrin receptor.Congenital anaemias due to ineffective erythropoiesis can be associated with excessive iron absorption and progressive iron loading (Finch, 1994). Life-threatening iron overload may occur in non-transfused patients with thalassaemia intermedia (Pippard et al, 1979), congenital dyserythropoietic anaemia type II (CDA II) (Cazzola et al, 1983) and X-linked congenital sideroblastic anaemia (XLSA) (Cazzola et al, 1983;Peto et al, 1983). The degree of anaemia has been shown to be a poor predictor of iron loading, which correlates better with erythroid marrow activity. In fact studies of erythropoiesis and iron balance in anaemic patients have shown that expanded erythropoiesis is associated with increased iron absorption (Pootrakul et al, 1988).The mechanism by which the erythroid marrow expansion induces a positive iron balance is unknown (Finch, 1994). Recent observations suggest that HFE, an MCHrelated protein which is mutated in genetic haemochromatosis (Feder et al, 1996), may regulate iron homeostasis by interacting with transferrin receptor (TfR). HFE protein, in fact, binds to TfR with high af®nity and decreases binding of diferric transferrin . In addition, soluble TfR and HFE bind tightly at the basic pH of the cell surface, but not at the acidic pH of intracellular vesicles (Lebron et al, 1998).A soluble form of TfR, probably representing a truncated form of tissue receptor, is present in human plasma (Huebers et al, 1990). The erythroid marrow is its main source and the soluble TfR concentration is increased in conditions with erythroid hyperplasia. We investigated whether the level of soluble TfR was related to the degree of iron overload in a group of patients with congenital anaemia due to ineffective erythropoiesis. PATIENTS AND METHODSWe studied 20 patients with thalassaemia intermedia, six patients with CDA II and four patients with XLSA who had received no or only occasional blood transfusions; their ages ranged from 7 to 66 years. The 20 patients with thalassaemia intermedia were followed at the Haematology Department of the Istituto di Clinica e Biologia dell'Eta Á Evolutiva, University of Cagliari, Sardinia, Italy. All were of Sardinian descent and ful®lled accepted criteria for a diagnosis of thalassaemia intermedia. The six patie...