Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

BACKGROUND AND OBJECTIVE: Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. DESIGN AND METHODS: A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb <= 100 g/L or receiving transfusions and serum erythropoietin <= 250 U/L. These patients were treated with subcutaneous rHuEpo (300 U/kg) three times a week for 8 weeks. In the case of partial response (PR) or no response (NR) subcutaneosly administered G-CSF (1 microg/kg) three times a week was added to the rHuEpo for 8 more weeks. If the patient achieved complete response (CR) or PR in the second phase, he was included in a follow-up phase of 24 weeks in which the dose of growth factors was tapered down. Several variables, including the score published by the Scandinavian-American group, were used as possible predictive variables. RESULTS: An erythroid response was observed in 16 patients (50%); in 12 it was a CR and in 4 it was a PR. During the period of rHuEpo administration, 7 CR and 4 PR (34.4%) were documented. Of the 14 patients in whom G-CSF was added to rHuEpo, 7 (50%) responded (3 CR and 4 PR). No major side-effects associated with growth factors were observed. The multivariate analysis showed that of the different variables evaluated only the Scandinavian-American response score was significant with a relative probability of response of 11.8 (95% confident intervals: 2.5-53) when this score was > +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. INTERPRETATION AND CONCLUSIONS: Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

Red blood cell phenotypes in alpha-thalassemias in the Spanish population.

BACKGROUND AND OBJECTIVE: alpha-thalassemia is very common on all thalassemic geographical regions. The present work aimed at analyzing the relationship between the degree of microcytosis and hematological parameters and the type of alpha-thalassemic mutation. DESIGN AND METHODS: Five hundred and thirty-six subjects with 4 kinds of alpha-thalassemia were examined using established techniques that determined all hematological parameters, and globin synthesis and molecular biological techniques to study the DNA of globin genes by Southern blotting. RESULTS: Adult carriers of alpha (+)-thalassemia (-alpha/alpha alpha) present very few hematological alterations. In a statistical comparison with normal individuals (alpha alpha/alpha alpha), significant differences were found between the hemocytometric data and the MCV and MCH of heterozygous alpha + thalassemia and the heterozygous alpha zero or homozygous alpha + genotype. Hb H disease was detected in 15 patients, presenting a severe degree of anemia, a significant increase in RDW and globin chain synthesis with an alpha/beta ratio of 0.5 +/- 0.1. INTERPRETATION AND CONCLUSIONS: These data provide reference values for geographical areas where alpha + thalassemia is common. These hematocytometric data, together with hemoglobin analysis, could be useful as a future reference data for new patients diagnosed with alpha-thalassemia.

Family history as an independent risk factor for ischaemic heart disease in a low incidence area (Galicia, Spain).

It has been suggested that a family history positive for coronary heart disease (CHD) increases the risk of CHD. We studied this association to determine the degree of risk, the independence of this association and the presence of interaction of a family history of CHD with the major known risk factors in a low incidence area. One hundred and six hospital cases (85 males and 21 females) of CHD and 106 hospital controls individually matched with each case for sex, age and place of residence (rural-urban) were studied. From every participant, information was collected on their personal and family history of cardiovascular disease and risk factors; height, weight, lipid profile and blood pressure were measured, and an electrocardiogram was recorded. Conditional logistic regression was used in the analysis. The observed odds ratio of patients suffering from CHD among those with, compared to those without, a positive family history of CHD was 4.95 (95% confidence interval = 1.27-19.28) after adjusting for the major known risk factors in each individual and their families (no interaction term remained in the model). The results support the hypothesis that a family history of CHD, acting through mechanisms other than known risk factors or their familial aggregation, is an independent risk factor for CHD even in a low incidence area. No interaction effect was observed between family history and the presence of the three major risk factors of CHD. This should help to identify individuals at greater risk of CHD.

[A case-control study of risk factors of acute cerebrovascular disease]. / Estudio de casos y controles de factores de riesgo de accidente cerebrovascular agudo.

BACKGROUND: Stroke is the cardiovascular disease which causes the greatest number of deaths in Galicia, mortality, particularly in women, being higher than in the rest of Spain. The aim of this study was to investigate the risk factors of stroke and its importance in Galicia. METHODS: A hospitalary study of cases and controls was performed including 76 patients with stroke and 76 controls individually paired for age, sex, population habitat and date of admission with anamnesis, weight, height and blood pressure, analysis and electrocardiogram being carried out in all. RESULTS: An association was found between the disease and family history of stroke (odds ratio = 3.6, confidence interval 95% = 1.2-13.3), personal history of stroke (17.9; 4.0-79.1), personal history of atrial fibrillation (15.0; 3.3-68.3), high blood pressure (4.5; 1.9-11.6) and ingestion of alcohol greater than or equal to 80 g/day in comparison with abstemious patients adjusted for the effect of high blood pressure (2.5; 1.1-5.7). An association was also observed with serum cholesterol levels greater than or equal to 250 mg/dl (6.46 mmol/l) (3.3; 1.2-8.8, in comparison with cholesterol less than 200 mg/dl). No association was found with the cigarette smoking (1.2; 0.7-2.3). CONCLUSIONS: The results observed for high blood pressure and the ingestion of alcohol regardless of the same are of importance in primary prevention due to being modifiable risk factors. The association with family history of stroke and auricular fibrillation reinforce the needs for primary prevention measures in these subpopulations while having had a stroke or a transitory ischemic attack is the characteristic with the most risk reinforcing the need for secondary prevention measures which have found to be effective. The controls presented abnormally low cholesterol levels that do not reflect those of the population from which they originate, thus existing the possibility that the association observed is spurious.

Hereditary hemorrhagic telangiectasia: analysis of platelet aggregation and fibrinolytic system in seven patients.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder characterized by the presence of generalized mucocutaneous and visceral telangiectasias associated with recurrent bleeding. In order to analyze the mechanism of bleeding in HHT we studied the hemostatic system and platelet in vitro aggregation in 7 unrelated patients suffering from HHT. Unlike the authors of previous reports, we could not find any significant alteration of the parameters measured suggesting a possible local role of the affected endothelial cells.

[The modified "pink test" in the diagnosis of hereditary spherocytosis]. / El "pink test" modificado en el diagnóstico de la esferocitosis hereditaria.

Hereditary spherocytosis is still difficult to diagnose in some situations due to the existence of subclinical expressions and the lack of an accurate test with high sensitivity and specificity. Recently, Vettore et al. described the so-called 'Pink test' as an easy method with the highest reproducibility and sensitivity. Herein, we present our experience with the 'Pink test' in the diagnosis of 16 previously diagnosed hereditary spherocytosis patients comparing the results with those obtained in 96 healthy controls, 41 beta-thalassaemias, 9 autoimmune haemolytic anaemias, 8 chronic hemoproliferative syndromes and 2 patients with pyruvate kinase deficiency. We also present a modification of the original 'Pink test' in which a small sample of blood (200 microL) obtained by finger-prick (or heel puncture in newborns and infants) is mixed with the hemolyzing solution of the 'Pink test' within the first three hours after blood drawing. Elevated correlation coefficients (r = 0.75-0.96) between both methods have been obtained comparing the percentage of final haemolysis in 25 healthy controls, 21 beta-thalassaemia minor and 9 hereditary spherocytosis patients.