Amal El Beshlawy

UNLABELLED: Background Following a clinical evaluation of deferasirox (Exjade) it was concluded that, in addition to baseline body iron burden, ongoing transfusional iron intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an iron chelator, is the first to evaluate whether fixed starting doses of deferasirox, based on transfusional iron intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation in patients (aged >or=2 years) with transfusional hemosiderosis from various types of anemia.

DESIGN AND METHODS: The recommended initial dose was 20 mg/kg/day for patients receiving 2-4 packed red blood cell units/month and 10 or 30 mg/kg/day was recommended for patients receiving less or more frequent transfusions, respectively. Dose adjustments were based on 3-month serum ferritin trends and continuous assessment of safety markers. The primary efficacy end-point was change in serum ferritin after 52 weeks compared with baseline.

RESULTS: The 1744 patients enrolled had the following conditions; thalassemia (n=1115), myelodysplastic syndromes (n=341), aplastic anemia (n=116), sickle cell disease (n=80), rare anemias (n=43) and other transfused anemias (n=49). Overall, there was a significant reduction in serum ferritin from baseline (-264 ng/mL; P<0.0001), reflecting dosage adjustments and ongoing iron intake. The most common (>5%) adverse events were gastrointestinal disturbances (28%) and skin rash (10%). Conclusions Analysis of this large, prospectively collected data set confirms the response to chelation therapy across various anemias, supporting initial deferasirox doses based on transfusional iron intake, with subsequent dose titration guided by trends in serum ferritin and safety markers (clinicaltrials.gov identifier: NCT00171821).

Patient-reported outcomes of once-daily oral deferasirox (Exjade) in iron-overloaded patients with beta-thalassemia not achieving successful chelation with prior deferoxamine and/or deferiprone were investigated in a prospective, open-label, 1-year, multicenter study in the Middle East (ESCALATOR). The initial dose of deferasirox was 20 mg/kg/day, with subsequent dose adjustments. At baseline and the end of study (EOS), patients (n = 237) completed a 5-point rating scale for treatment satisfaction and convenience, and recorded time lost to treatment. At EOS, 90.7% of patients were 'satisfied'/'very satisfied' with their iron chelation therapy (ICT) versus 23.2% at baseline. 92.8% (EOS) versus 21.5% (baseline) of patients considered their therapy to be 'convenient'/'very convenient'. Time lost to therapy for daily activities was substantially reduced (3.2 +/- 8.6 [mean +/- SD; EOS] vs. 30.1 +/- 44.2 [baseline] h/month). Patients reported greater satisfaction and convenience, and lower impact on daily activities, with deferasirox than with previous ICT. This may help improve adherence to lifelong ICT in iron-overloaded beta-thalassemia patients.

OBJECTIVES: Cell populations residing in waste tissues (cord blood, umbilical cord, and placenta) may be collected without any medical or ethical contraindications concerning the mother or newborn baby. Cord blood hematopoietic stem cells are routinely used for clinical transplants; however, the low cell dose of the graft limits their therapeutic efficacy as it is associated with increased delayed or failed engraftment. The cell dose can be increased, and the efficacy of cord blood transplant potentially improved, by ex vivo expansion before transplant.

MATERIALS AND METHODS: Twelve umbilical cord blood samples were included. The effect of cord blood storage at -80 degrees C on CD34+ cell count (mean -/+ standard deviation [SD]), cell viability (mean -/+ SD percent), and cell cycle status (percent quiescent versus dividing) was estimated. Ex vivo culture of cord blood mononuclear cells was done before storage, and after 1 week of freezing, and after 2 weeks of freezing. Ex vivo liquid culture was performed with media supplemented with stem cell factor, interleukin-3 (IL-3), and both.

RESULTS: The count of CD34+ cells in pre-expansion aliquots decreased from 15.00 +/- 9.96 x 106 cells before freezing to 7.70 -/+ 3.20 x 106 cells after 2 weeks of freezing (P = .024). Cell viability in pre-expansion aliquots decreased from 99.5% -/+ 1.0% before freezing, to 52.5% -/+ 27.5% after 1 week of freezing (P = .013) and to 32.5% -/+ 9.5% after 2 weeks of freezing (P = .001). Mean fold of cell expansion and proportion of quiescent versus dividing cells did not change significantly from before to after freezing, and was not significantly different for culture with stem cell factor, IL-3, or both.

CONCLUSION: Although freezing decreased cell count and viability, it did not impair the expansion potential of cord blood hematopoietic cells. Whether IL-3 or stem cell factor should be considered as essential components of expansion media is uncertain.

OBJECTIVE: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20-30 mg/kg/d reduces iron burden, depending on transfusional iron intake.

METHODS: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients > or =2 yr with beta-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of > or =3 mg Fe/g dry weight (dw) if baseline LIC was > or =10 mg Fe/g dw, or final LIC of 1-7 mg Fe/g dw for patients with baseline LIC of 2 to <10 mg Fe/g dw.

RESULTS: Overall, 233/237 enrolled patients completed 1 yr's treatment. Mean baseline LIC was 18.0 +/- 9.1 mg Fe/g dw, while median serum ferritin was 3356 ng/mL. After 1 yr's deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment.

CONCLUSIONS: The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with beta-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden.

Hemoglobin (Hb) disorders are common, potentially lethal monogenic diseases, posing a global health challenge. With worldwide migration and intermixing of carriers, demanding flexible health planning and patient care, hemoglobinopathies may serve as a paradigm for the use of electronic infrastructure tools in the collection of data, the dissemination of knowledge, the harmonization of treatment, and the coordination of research and preventive programs. ITHANET, a network covering thalassemias and other hemoglobinopathies, comprises 26 organizations from 16 countries, including non-European countries of origin for these diseases (Egypt, Israel, Lebanon, Tunisia and Turkey). Using electronic infrastructure tools, ITHANET aims to strengthen cross-border communication and data transfer, cooperative research and treatment of thalassemia, and to improve support and information of those affected by hemoglobinopathies. Moreover, the consortium has established the ITHANET Portal, a novel web-based instrument for the dissemination of information on hemoglobinopathies to researchers, clinicians and patients. The ITHANET Portal is a growing public resource, providing forums for discussion and research coordination, and giving access to courses and databases organized by ITHANET partners. Already a popular repository for diagnostic protocols and news related to hemoglobinopathies, the ITHANET Portal also provides a searchable, extendable database of thalassemia mutations and associated background information. The experience of ITHANET is exemplary for a consortium bringing together disparate organizations from heterogeneous partner countries to face a common health challenge. The ITHANET Portal as a web-based tool born out of this experience amends some of the problems encountered and facilitates education and international exchange of data and expertise for hemoglobinopathies.

Thalassemia patients with persistently high levels of fetal globin typically have less severe anemia, have milder clinical syndromes, and are often transfusion independent. Therefore, the search for molecules exhibiting the property of inducing gamma-globin gene expression and fetal hemoglobin (HbF) production is of great interest. Different pharmacological agents have been studied, namely erythropoietin, short chain fatty acids and cytotoxic agents, azacytidine, and hydroxycarbamide. Hemoglobin F inducers from natural plants, such as angelicin and resveratrol, are powerful inducers of erythroid differentiation and increase HbF in erythroid progenitors of thalassemia patients. Induction of HbF in beta-thalassemia patients is expected to be crucial for developing countries unable to sustain the high cost of clinical management of beta-thalassemia patients.

The hemoglobin disorders are the most common clinically serious single gene disorders in the world. In Egypt, beta-thalassemia is the most common type with a carrier rate varying from 5.3 to > or =9% and a gene frequency of 0.03. So, it was estimated that 1,000/1.5 million per year live births will suffer from thalassemia disease in Egypt (total live births 1,936,205 in 2006). beta-Thalassemia creates a social and financial burden for the patients' family and the Egyptian government. The high frequency of beta-thalassemia carriers with increasing rate of newly born cases is a pressing reason for the importance to develop prevention program for beta-thalassemia in Egypt. Sickle-cell disease (SCD) is not frequent in Egypt except in the Oases where the carrier rate varies from 9 to 22%. Our objectives were to provide an in-depth analysis of the current status of hemoglobinopathies in Egypt and what we need for prevention of these diseases.

Patients with thalassemia major requiring regular blood transfusions accumulate iron that is toxic to the heart, liver, and endocrine systems. The following prospective, randomized trial was carried out to determine the effectiveness, in children and young adults, of combined deferiprone (DFP) and deferoxamine (DFO) in reducing transfusional iron overload compared to either drug alone and to assess the safety and tolerability of DFP. Sixty-six patients were randomized into three treatment arms: daily DFP combined with DFO twice weekly; daily DFP only; and DFO only 5 days/week. Fifty-six patients completed the 54 weeks and were assessed by different indices. A significant reduction of liver iron concentration and serum ferritin was observed in all three arms while significant reduction of liver iron score was observed in patients on combination therapy only. Cardiac function did not significantly change in any arm. Compliance improved in patients who received combined therapy. Toxicity of DFP was mild to moderate and acceptable; most commonly, transient arthropathy and nausea/vomiting were observed. Thus, combination therapy has shown to be effective in reducing iron overload in thalassemia patients.

OBJECTIVE: To investigate puberty in a group of thalassemic patients with delayed or arrested pubertal development and to compare the effects of hormonal and L-carnitine therapy on puberty in those patients.

PATIENTS: Thirty-two -thalassemic patients with arrested or failure of puberty were enrolled for 1 year in this study.

METHOD: Clinical pubertal assessment and laboratory investigations were done for all patients at the beginning, 6 months later clinical pubertal assessment was done. Patients were divided into two groups (16 each): first group received L-carnitine therapy, while the second group received hormonal therapy. Pubertal and laboratory assessment were done 6 months after hormonal and L-carnitine therapy.

RESULTS: Failure of puberty was confirmed in 71.4% of boys and 33.3% of girls, while arrested puberty was observed in 28.6% of boys and 66.7% of girls. All girls had amenorrhea, primary amenorrhea in 88.9% and secondary amenorrhea in 11.1%. Menses occurred in 20% of female patients after L-carnitine therapy and in 37.5% of them after hormonal therapy. Improvement of pubertal staging was observed in 50% of males after L-carnitine therapy compared to 75% of them after hormonal therapy. While improvement of pubertal staging was seen in 90% of females after L-carnitine therapy compared to 100% of females after hormonal treatment. However, these results showed no significant difference between both groups.

CONCLUSION: Delayed puberty in beta-thalassemia major is either due to failure of gonads or failure of the whole hypothalamic pituitary gonadal axis. L-carnitine as well as hormonal replacement therapy had a positive effect on puberty in the thalassemic patients. Further studies are needed to clarify the role of L-carnitine on puberty in these patients.

Cardiac complications, such as pulmonary hypertension (PHT), are the leading cause of death in beta-thalassemia patients. L-Carnitine, due to its role in fatty acid oxidation, might help control the elevation in pulmonary artery systolic pressure (PASP). The objectives of this study were to assess the prevalence of PHT in beta-thalassemia major patients, identify clinical predictors for its development, and determine the potential effects of L-carnitine. In total, 32 patients with beta-thalassemia major were recruited; 16 age- and sex-matched children constituted the control group. Cardiac evaluation was performed by using echocardiography. The patients with PHT received 50 mg/kg/day L-carnitine orally for 3 months and were then reevaluated. Based on PASP, the patients were divided into group A without PHT and group B with PHT. The prevalence of PHT was 37.5%. The other echocardiographic measurements were not significantly different between groups A and B. PASP did not have any significant correlation with the following variables: age, total number of blood units received, splenic status, serum ferritin level, and ejection fraction. Following the administration of L-carnitine, there was a significant decrease in the mean PASP from 33.96 +/- 7.85 to 24.11 +/- 7.61. All cardiac dimensions decreased following L-carnitine, but the changes were not statistically significant. Even though beta-thalassemia major resulted in an elevation in the PASP in only a fraction of the patients, it seems to have an impact on the heart dimensions and function of all patients. No clinical predictors were identified. Oral administration of L-carnitine appears to significantly improve PASP.

The splicing mutation in intron 1 of beta-globin gene (IVS1-110) is the most common mutation in Egyptian thalassemics that causes aberrant splicing of pre-mRNA and deficient beta-globin chain synthesis. Antisense oligonucleotides (ASONs) are compounds that redirect pre-mRNA splicing and modify gene expression. Our aim was ex vivo correction of the aberrant splicing of beta-globin110 pre-mRNA by ASON against the 3' aberrant splice site. Peripheral blood mononuclear cells of 10 thalassemic patients with IVS1-110 mutation were duplicated and 1 was treated with 20 micromoL/mL morpholino ASON targeted against the 3' aberrant splice site. The level of total hemoglobin (Hb), fetal Hb, and mRNA were estimated in the duplicate samples. Five cases (50%) showed correction with ASON treatment, of which 2 cases showed the appearance of corrected mRNA band with absence of the aberrant band and 3 cases showed an increased ratio of the corrected to the aberrant mRNA band from 2:1 to 3:1, and 4:1. The total Hb showed significant increase in the 5 corrected cases. In conclusion, ASON can restore correct splicing of beta-globin pre-mRNA leading to correct gene product in cultured erythropoietic cells. These results suggest the applicability of ASON for the treatment of thalassemia.

Poor physical fitness is a common problem among thalassemic patients. L-Carnitine plays an essential role in fatty acid beta-oxidation, a process especially important in the organs that preferentially use fatty acid as a source of energy such as the myocardium and the skeletal muscles. The main objective of this study is to assess the effect of the administration of oral L-carnitine on exercise tolerance and physical fitness in patients with thalassemia major. Thirty patients followed up at the New Cairo University Children Hospital were included in this study. Clinical, laboratory, and cardiopulmonary exercise testing were performed before and after 6 months of oral L-carnitine therapy (50 mg/kg/day). The oxygen consumption, cardiac output, and oxygen pulse at maximal exercise significantly increased after L-carnitine therapy (p<0.001, p=0.002 and p<0.001, respectively). However, there was no significant change in minute ventilation and ventilatory equivalent of carbon dioxide (p=0.07 and p=0.06, respectively). A weak but positive correlation between the age of the patients and the degree of improvement in exercise parameters was noted. There was also significant increase in the blood transfusion intervals after L-carnitine administration (p=0.008). However, there was no significant change in hemoglobin concentration (p=0.4). L-Carnitine seems to be a safe and effective adjunctive therapeutic approach in thalassemic patients. It improves their cardiac performance and physical fitness. The younger the patients are, the higher is the degree of improvement in their exercise parameters.

Iron overload is a potentially fatal complication in thalassemia patients. Accurate assessment of body iron is of utmost importance for these patients. The available methods for iron stores evaluation have limitations. We assessed biochemically the skin iron concentration (SIC) and determined the relation between the hepatic and skin iron level in thalassemia major patients to develop a simple, sensitive, quantitative measure of the body iron stores. Thirty-one cases with thalassemia major were assessed for iron overload. Liver and skin biopsies were performed for the patients and skin biopsies were taken from the 31 controls. The biopsies were subjected to biochemical assay of iron and histologic sections were examined. The SIC of the studied cases was significantly higher than that of the control group with a mean of 2.705 +/- 1.14 and 0.275 +/- 0.13 mg/g dry skin weight, respectively, p < 0.001. There was significant correlation between the SIC and the liver iron concentration (LIC) (r = 0.43, p = 0.01). The amount of liver iron is equivalent to [(3.5 x SIC) + 12.9]. With the use of this equation, we could reliably estimate an LIC value as high as 21.2 mg/g dry liver weight with a standard error of 4.07. Biochemical assay of the skin iron concentration is a reliable quantitative indicator of the body iron stores in patients with thalassemia major.

The aim of this study was the molecular characterization of beta-thalassemia (thal) mutations in a group of 95 Egyptian thalassemic patients from Fayoum in Upper Egypt, Cairo, Alexandria and Tanta in Lower Egypt and the Nile Delta. To identify these anomalies, the polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) technique was used, complemented by direct DNA sequencing for uncharacterized cases. In 80 of the 95 patients, the beta-thal mutation was detected by PCR-ARMS. The most common allele encountered in our study was IVS-I-6 (T-->C) (36.3%); the second most common mutation was IVS-I-110 (G-->A) (25.8%). In addition, we report three homozygous cases for the promoter region -87 (C-->G) allele with a frequency of 3.2%. DNA sequencing of uncharacterized cases (14 cases, 15 alleles) revealed six cases (six alleles) of codon 27 (G-->T), and three cases (three alleles) of the IVS-II-848 (C-->A) mutation. Codon 37 (G-->A) in the homozygous state was found in one patient with positive consanguinity. The frameshift codon 5 (-CT) mutation was detected in two of our uncharacterized cases. The codon 15 (TGG-->TGA) mutations was detected in one patient (one allele, 0.5%). All studied cases were fully characterized by this strategy. Screening for beta-thalassemic mutations using ARMS-PCR for the seven most frequent alleles in Egypt succeeded in determining the beta-globin genotype in 84.2% of our patients (91.6% of the expected alleles). To improve the efficiency of routine screening, the PCR-ARMS mutation panel should be updated to include the reported rare alleles. Direct DNA sequencing is an additional way to allow a full characterization of beta-thal patients in the Egyptian population.

BACKGROUND: Thrombopoietin (TPO) is a growth factor that controls platelet production. Despite the known association of chronic hypoxia and acute asphyxia with hematologic changes, TPO had not been studied in neonatal asphyxia.

OBJECTIVE: To assess TPO concentrations in the serum of asphyxiated and nonasphyxiated neonates, and examine any correlation with the severity of asphyxia.

DESIGN/METHODS: This prospective study was carried out on 32 asphyxiated neonates and 30 control subjects admitted at Cairo University Medical Center. Asphyxia was defined if two of the following were found: (1) Apgar score /=-10 and (3) clinical evidence of perinatal asphyxia. Encephalopathy was classified clinically according to Sarnat's stages during the first day of life. Platelet count and TPO level (pg/ml) were measured at 1st, 3rd and 7th day of life.

RESULTS: : TPO measured on the first day of life did not differ between cases and controls (900.2+/-526.4 vs 726.6+/-441.9 pg/ml, p=0.2). It increased on the 3rd day of life and was significantly higher in asphyxiated infants compared to controls (1291.4+/-627.9 vs 885.5+/-400.3 pg/ml, respectively; p=0.004). This difference remained significant in a logistic regression model controlling for birth weight, sex and mode of delivery (regression coefficient=476.9+/-146.8; p=0.002). In asphyxiated infants (n=32), encephalopathy was classified as mild (n=17), moderate (n=10) and severe (n=5). TPO correlated with the degree of clinical severity on the 7th day of life (r=0.59, p=0.003). TPO did not differ between survivors (n=24) and nonsurvivors (n=8) within the asphyxia group (1197.1+/-596.8 vs 1613.1+/-605.9 pg/ml; p=0.09). Platelet counts correlated negatively with TPO measured on day 1 (r=-0.415; p=0.02), day 3 (r=-0.64; p=0.001) and day 7 (r=-0.562; p=0.007).

CONCLUSIONS: TPO increased and correlated with severity of asphyxia at 3 and 7 days of life. It correlated negatively with the platelet count at all times.

As no physiological mechanism exist for excreting transfusional iron overload in thalassemia, chelation therapy is the mandatory way to remove iron to prevent end organ damage and prolong survival. Desferoxamine (DFO) has been the major iron chelating agent used extensively worldwide for more than three decades for treatment of transfusional iron overload. However compliance has been a major obstacle in achieving an optimal therapeutic results. During the last 20 years the search for an affective oral iron chelators alternatives to Sc. DFO has been intensive. Different compounds have been studied, most of them although effective in animals have shown unacceptable toxicity with the exception of Deferiprone (L1) and ICL670.

OBJECTIVE: The aim of this study was to clarify the effect of hypoxia on the physiologic inhibition system of coagulation including protein S, protein C, and antithrombin III and to study their effect on thromboembolic accidents of hypoxic newborns.

DESIGN: Clinical study including ten hypoxic-ischemic neonates and ten normal neonates as a control group.

DATA SOURCES: MEDLINE, pediatric textbooks, neonatal intensive care unit, Department of Paediatrics, Faculty of Medicine, Cairo University.

RESULTS: The results of this study revealed a marked decrease in the level of the physiologic inhibition system of coagulation including antithrombin III, protein C, and protein S in 100% of the hypoxic-ischemic neonates compared with the control group (p <.001) before the occurrence of thromboembolic complications. Fifty percent of the hypoxic-ischemic neonates developed disseminated intravascular coagulation and died, 40% developed necrotizing enterocolitis and rectal bleeding, 20% developed hematuria, 30% developed hematemesis, 20% developed intracranial hemorrhage, and 100% had convulsions.

CONCLUSIONS: In this study, we evaluated the effect of asphyxia on the physiologic inhibition system of coagulation in neonates. Care providers should suspect hypoxia resulting from any obstructed labor and perform the necessary laboratory investigations for coagulation, including antithrombin III, protein C, and protein S levels, to help prevent thromboembolic accidents in asphyxiated neonates, including disseminated intravascular coagulation, necrotizing enterocolitis, and intracranial hemorrhage. Based on the development of antithrombin III and protein C concentrates, which are commercially available, require minimal monitoring, and have very few side effects, the time is ripe for evaluation of optimal treatment for thromboembolic accidents after neonatal asphyxia. This could be even more important if successful neuroprotectant strategies are also developed.

INTRODUCTION: Heart disease secondary to chronic anemia and hemosiderosis remains the major cause of morbidity and mortality in thalassemic patients. Chronic anemia and the tissue hypoxia it induces impair free fatty acid oxidation and ATP production in myocardial cells. The use of L-carnitine, a butyric acid derivative, may help overcome some of these defects.

OBJECTIVE: To investigate the effect of L-carnitine therapy on cardiac function in thalassemia major patients.

MATERIALS AND METHODS: Cardiac function was evaluated in 30 patients attending our clinic. The mean (+/-SD) age was 15.87 +/- 3.19 years. The studies we performed included echocardiography, Doppler and multigated equilibrium radionuclide angiography (MUGA). Systolic and diastolic function was evaluated before starting L-carnitine treatment and after 6 months of oral L-carnitine (50 mg/kg/day).

RESULTS: Echocardiography studies revealed no significant changes in systolic and diastolic function after L-carnitine therapy (p > 0.05). Analysis of the data taken by MUGA performed in 20 of the patients, however, showed a significant improvement of diastolic function after 6 months of L-carnitine therapy. The mean peak filling rate (end-diastolic volume/s) increased from 3.15 +/- 1.06 to 3.61 +/- 1.68 (p < 0.03). The time to peak (during filling) decreased significantly from 143.45 +/- 42.04 to 117.70 +/- 24.40 s (p < 0.02). Systolic function showed a significant increase in the left ventricular ejection fraction from 58.25 +/- 9.92 to 63.95 +/- 10.11% (p = 0.0001).

CONCLUSION: L-carnitine may be an effective drug for improving the cardiac status of thalassemic patients. MUGA is the most accurate technique of those used here for assessing left ventricular function in these patients.

OBJECTIVE: Diamond-Blackfan anemia is a rare congenital hypoproliferative anemia of infancy and early childhood. Treatment with corticosteroids is commonly used, but with limited success. Trials with cyclosporin-A (CSA) are not frequently reported. Therefore, in this study we analyzed our results in the management of this rare disease by different medical treatments.

DESIGN: The results of 22 patients diagnosed at our Hematology Center in the New Cairo University Children's Hospital during the period 1991-2001 were retrospectively analyzed. Our patients first received prednisolone (2 mg/kg/d) for different courses according to their response. Since the year 2000, the steroid nonresponders received CSA (3-12 mg/kg/d) for 6 months unless treatment complications developed.

RESULTS: The age at the onset of the disease ranged from 1 to 24 months (median: 2.5 months). The mean values of the hemoglobin, the reticulocyte count, and the myeloid/erythroid ratio at the onset of the disease were 4.75 +/- 1.79 g/dL, 0.14 +/- 0.16, and 39.4 +/- 27.08, respectively. Patients received prednisolone from 0.25 to 10 years (median: 2 years). Ten patients were nonresponders (45.5%), and 5 patients (22.7%) responded to corticosteroid therapy. Two of 5 responders are off treatment with a hemoglobin level of >9 g/dL, and 3 of 5 are currently corticosteroid-dependent. Of 10 patients not responding to steroids, 8 received CSA for 6 months. Four patients (50%) responded to CSA therapy. A significant positive association was found between CSA dose and response.

CONCLUSION: CSA therapy should be tried in steroid-resistant Diamond-Blackfan anemia patients before blood transfusion or corticosteroid therapy complications are instituted.