Hydroxyurea therapy in thalassemia.

The clinical effectiveness of Hydroxyurea in thalassemia is still controversial. The present paper puts together the authors' experience in two groups of patients with thalassemia intermedia and sickle cell/beta-thalassemia treated with varying dosages of hydroxyurea over several months. A third group received hydroxyurea along with recombinant human erythropoietin. Our observations are summarized in that treatment with hydroxyrea results in a significant increase of fetal hemoglobin with no change of the total hemoglobin levels. The drug causes also a considerable increase of the erythrocyte volume and hemoglobin content while the MCHC values remain unchanged. As a rule, and without objective criteria so far, patients state feeling better and having more energy. The authors postulate that this feeling may reflect the significant decrease of ineffective erythropoiesis resulting by the replacement of the poorly hemoglobinized, prematurely dying erythroid progenitor and red cell population by another population of cells with higher hemoglobin content and longer survival, the regeneration of which requires less energy and consumption. As expected, patients with sickle cell/beta-thalassemia have also fewer crises and painful episodes. The above findings are in keeping with the few available reports in the literature.

The clinical phenotype of beta and delta beta thalassemias in Greece.

Based on precise evaluation of hematological findings and clinical manifestations, the relationship between genotype and clinical phenotype was studied in 475 Greek patients with beta and delta beta thalassemias. Almost all known genotypes are included in this series, but the most frequent was homozygous beta th high A2 (71.6%), beta th/beta th silent (7.4%), beta th/delta beta oth high F (6.3%) and beta th/beta th Dutch (6.3%). In general, the phenotype was related to the genotype, though clinical heterogeneity was detected among patients with the same genotype. The severe type of thalassemia major was most commonly found in homozygous beta th patients mainly of beta o/beta o and beta o/beta + genotypes while homozygous beta + patients had milder clinical manifestation. Furthermore a small group of patients, characterized as homozygous beta ++ (HbF less than 30%) had mild thalassemia intermedia. In addition mild thalassemia intermedia was principally related with homozygous delta beta oth, and compound heterozygous beta th/beta th silent I, and less frequently with other genotypes such as compound heterozygous with beta th/beta th Dutch, beta th/beta th silent II, beta th/delta beta oth high F or Lepore. It was shown that precise genetic characterization and clinical evaluation is of primary importance in predicting the prognosis and formulating the proper treatment for the individual patient with thalassemia.

Developmental changes in hemoglobin F levels during the first two years of life in normal and heterozygous beta-thalassemia infants.

To study the developmental pattern of hemoglobin F (HbF) during the first two years of life, levels of HbF were estimated in two groups of infants: 117 normal infants and 98 heterozygotes for beta-thalassemia, all aged between 1 and 24 months. The results may be summarized as follows: (1) Levels of HbF in beta-thalassemia heterozygotes were significantly higher than those of normal infants of the same age (P less than .01). (2) A reference curve for the decline of HbF in infants with beta-thalassemia trait was established to facilitate the diagnosis of heterozygotes during this period of life. (3) Hemoglobin A2 (HbA2) was also higher in beta-thalassemia heterozygotes than in normal infants of the same age. HbA2 increases with increasing age, reaching normal adult values at age 5 to 6 months. It is postulated that the higher level of HbF in heterozygous infants during the first two years of life is associated with the presence of the beta-thalassemia gene, which influences the increased synthesis of HbF in red cell.