Felicia Di Gregorio

SURVIVAL AND CAUSES OF DEATH IN THALASSAEMIA MAJOR

Survival and causes of death were studied in 1087 Italian patients with thalassaemia major who were born on or after Jan 1, 1960. At the age of 15 years, the Kaplan-Meier estimate of survival after the first decade of life was 80.6% for subjects born in 1960-64, 84.2% for those born in 1965-69, and 96.9% for those born in 1970-74. At the age of 20 years, survival from the age of 10 was 59.1% for patients born in 1960-64, and 70.2% for those born in 1965-69; at 25 years, survival from the age of 10 was 40.7% in the 1960-64 cohort. Overall survival from birth for patients born in 1970-74 was 97.4% at 10 years, and 94.4% at 15 years. The most common cause of death was heart disease, followed by infection, liver disease, and malignancy.

Survival and Disease Complications in Thalassemia Major

Abstract: We studied survival and disease complications in 1,146 patients with thalassemia major, born from January 1, 1960 to December 31, 1987. At last follow‐up, in March 1997, probability of survival to age 20 years was 89% and to age 25 years was 82% for patients born in the years 1970‐1974. Patients who died had a serum ferritin level, measured the year before death, significantly higher than those who survived. Diabetes was present in 5.4% of the patients; heart failure in 6.4%; arrhythmias in 5.0%, thrombosis in 1.1%, hypothyroidism in 11.6%, HIV infection in 1.8%. Hypogonadism was diagnosed in 55% of 578 patients who had reached pubertal age: 83.5% of hypogonadic females and 78.6% of males were receiving substitutive hormonal therapy. In conclusion, the survival of patients with thalassemia major is good and improving, but the prevalence of severe complications is still high.

An alternative to continuous subcutaneous infusion of desferrioxamine in thalassaemic patients

Sixteen patients with thalassaemia major were treated with subcutaneous desferrioxamine (DF) 50 mg/kg/d, 5 consecutive days a week, for 8 weeks. Every other week the total dose was administered by 12 h infusion pump or by rapid injection of the same dose (25 × 2 mg/kg) twice a day. The two methods of DF administration produced no significant differences in urinary iron excretion. No significant changes in serum ferritin levels were observed at the end of the study. Compared with continuous infusion, rapid injection is equally efficacious, does not induce serious side‐effects, is better accepted by the patients, and can improve their compliance to the iron‐chelating therapy.

Effect of Alpha-interferon on Natural Killer Cell Activity and Lymphocyte Subsets in Thalassemia Patients with Chronic Hepatitis C

The variation of natural killer (NK) cell activity and lymphocyte subsets 20 h after a single test dose of alpha-IFN, was studied in 17 thalassemic patients with chronic hepatitis C. All patients had suspended the alpha-IFN therapy at least 12 months before the study: 10 were considered responders and 7 nonresponders. Also NK cell cytotoxicity after in vitro incubation with alpha-IFN was studied. The administration of a single dose of alpha-IFN increased NK cell cytotoxic activity significantly in the group of responders and in non-responders; moreover the NK cell cytotoxic activity after alpha-IFN in vitro incubation increased both in responders and nonresponders, but to a lesser degree than in healthy controls. Absolute values of CD4+ and CD8+ lymphocytes decreased significantly only in responders. In conclusion, our data suggest that the variation of NK cytotoxic activity and lymphocyte subsets after a test dose of alpha-IFN can be considered a parameter related to IFN biological effects.

Interferon-α Therapy in Sicilian and Sardinian Polytransfused Thalassaemic Patients with Chronic Hepatitis C

AbstractObjective: Our study was designed to evaluate the effects of 2 dosage schedules of recombinant interferon (IFN)-α (IFNα-2a and IFNα-2b) in reducing serum ALT and eradicating serum hepatitis C virus (HCV) RNA in β-thalassaemic patients with chronic hepatitis C. Design: 38 Sicilian β-thalassaemic patients (22 males and 16 females) received intramuscular IFNα-2a (Roferon-A®; Roche) 5 MU/m2 3 times weekly for 6 months, followed by 3 MU/m2 3 times weekly for a further 6 months. 13 Sardinian β-thalassaemic patients (7 males and 6 females) received intramuscular IFNα-2b (Intron®; Schering-Plough) 3 MU/m2 3 times weekly for 12 months. Parallel control groups (n = 20 and n = 8, respectively) did not receive IFNα. All patients received continuous subcutaneous desferoxamine infusion. Results: 24 (63%) Sicilian patients had a positive clinical response to IFNα-2a therapy. Two different patterns of response were apparent: (i) early and progressive decrease in ALT values until stable normalisation; and (ii) slower reduction of ALT values, which fluctuated on the way to normalisation. Five (21%) patients relapsed during the 12-month follow-up period. ALT levels decreased early in 5 (38%) Sardinian patients and one patient (20%) relapsed during the 12-month follow-up period. In the control groups, ALT values spontaneously normalised in 3 (10%) untreated patients. None of the patients treated with IFNα developed anti-IFNα antibodies. Viral clearance was demonstrated in 19 (50%) of 38 patients in the Sicilian group and 4 of 13 patients (31%) in the Sardinian group. Conclusion: Treatment with intramuscular recombinant IFNα-2a 5 MU/m2 3 times weekly for 6 months, followed by 3 MU/m2 3 times weekly for 6 months, appeared to be more effective than intramuscular IFNα-2b 3 MU/m2 3 times weekly for 12 months.

Desensitization treatment for anaphylactoid reactions to desferrioxamine in a pediatric patient with thalassemia.

Desfernoxamine (DF), which is used to reduce iron overload in patients with thalassemia major, has been reported to elicit untoward reactions. A bibliographic search revealed that anaphylactoid reactions have been reported in four adult patients with thalassemia who were receiving DF for a long period and who were successfully treated by rapid desensitization. TM An anaphylactoid reaction to DF has been r eported in onty one child, who d id not receive rapid desensitization, but was treated with calcium diethylenetriami ne-pentaacetic acid. » In three cases 1-3 no immunologic studies were performed, but in the fourth case 4 a careful immunologic analysis was carried out. We report a case of anaphylactic reactions to DF in a very young child with thalassemia who underwent successful desensitization. We also report results of an immunologic study of the case.

Febrile and afebrile convulsions: a clinical follow-up

A joint study was performed on 204 children who suffered separate febrile (FS) and afebrile seizures (aFS) within a short space of time to evaluate the risk of subsequent convulsive crises. The data obtained revealed frequent recurrence of seizures and high risk of subsequent convulsive afebrile crises in these children.

Clinical and Molecular Heterogeneity of δ, β‐Thalassemia in Sicilya

6, P-Thalassemia is a heterogeneous group of hemoglobin disorders, characterized by the absence of 6 and P chains that is partially compensated by the increased production of y chains.”’ Homozygous patients generally show the clinical picture of P-thalassemia intermedia and their hemoglobin is composed only of Hb F.e9 Heterozygotes are clinically asymptomatic, having between 4 and 20% of Hb F irregularly distributed among their red cells and normal Hb A, Nevertheless, both homozygous and heterozygous conditions present the same red cell alteration of P-thalassemia. Studies on aand P-chain synthesis indicate that the degree of globin chain imbalance in 6, P-thalassemia is less than that seen in P-thalassemia.”-” The molecular defect has been identified in the deletion of 6 and P genes within the non-a-globin complex on chromosome 11.’”” 6, P-Thalassemia has been divided into two groups depending on the amount of gene deletion and the structural analysis of Hb F. One has both G, and k, chains (G,, A,.-& P-thalassemia) while only G, chains are produced (G,6, 0-thalassemia) in the other.’”’’ Consequently the phenotypic effects of 6, P-thalassemia correlate with the position and extension of the gene deletion: the cluster of four closely linked genes being in the order 5’G74-6/3-3’ on chromosome 11. Recently, both Cao et aL in Sardiniam and our group” simultaneously in Sicily described a new form of 6, 0-thalassemia (h-GP-Th), where the molecular defect did not seem due to either 6 and P gene deletion, or to gross rearrangement within the non-a-globin cluster.*’ The heterozygous condition is different from the standard G, and G,, A,6, P-thalassemia because of its lower synthesis of Hb F (8%), which is irregularly pancellularly distributed in the red cells.