Continuation of deferiprone therapy in patients with mild neutropenia may not lead to a more severe drop in neutrophil count.

Approximately 6% of patients with thalassemia receiving deferiprone develop neutropenia. Present practice is to monitor absolute neutrophil count (ANC) weekly and to interrupt treatment at the first sign of neutropenia, lest continuation lead to progressive neutrophil reduction. In a 6-month study evaluating the safety and efficacy of a liquid form of deferiprone in 100 children, ANC was initially checked weekly for all patients. For individuals experiencing mild neutropenia, deferiprone was continued but monitoring was increased to daily until resolution. Therapy was to be suspended only if the episode was prolonged or if it worsened. Four patients experienced single episodes of mild neutropenia, and two others each experienced two episodes. All eight episodes resolved within 4-7 d despite continued therapy. (One patient later developed agranulocytosis and had treatment terminated.) This study showed that not all cases of mild neutropenia during deferiprone therapy develop into agranulocytosis, and suggests that many may not be caused by deferiprone. Transient declines in ANC to levels defined as neutropenic are common even in healthy individuals, particularly children; and it could be that the frequent monitoring of ANC mandated during deferiprone therapy may reveal cases of transient neutropenia that would otherwise have gone undetected and resolved on their own without clinical consequences. In patients with thalassemia, several factors increase the probability of a transient fall in ANC. These findings raise the question of whether deferiprone should be routinely stopped in cases of mild neutropenia, provided that such patients have their ANC monitored more frequently during the neutropenic episode.

Hemihydranencephaly syndrome: case report and review.

BACKGROUND: Hemihydranencephaly (HHDNC) is a rare disorder with complete or almost complete unilateral absence of cerebral cortex. METHODS: This study describes a 27 months-old girl presenting with developmental delay and generalized weakness more on the left side. Bilateral blindness was noted since the age of 6 months. RESULTS: Her fundus examination revealed bilateral optic atrophy, dilated tortuous retinal veins with increased intra-ocular tension. She had polyuria and recurrent attacks of dehydration due to neurogenic diabetes insipidus. Her blood protein S was deficient. Her magnetic resonance imaging (MRI) demonstrated HHDNC with nearly complete absence of the right cerebral hemisphere. Her MR-Arteriography demonstrated total occlusion of right middle and anterior cerebral arteries and attenuated and beaded right posterior cerebral artery. Diffusion tensor MR imaging revealed complete absence of right cortico-spinal and optic tracts with deficient left sided tracts. CONCLUSION: In contrast to the good outcome of the few reported cases of HHDNC, this case had severe global disabilities.

N-terminal natriuretic peptide and ventilation-perfusion lung scan in sickle cell disease and thalassemia patients with pulmonary hypertension.

The aim of this study was to determine the prevalence of pulmonary hypertension (PH) in sickle cell disease and thalassemia patients in relation to clinical and laboratory parameters of hemolysis and hemosidersosis, as well as plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP). The study also aimed to define the role of thromboembolic pulmonary artery (PA) obstruction in its etiology. Forty sickle cell disease and 30 thalassemia patients [15 beta-thalassemia major (beta-TM) and 15 beta-thalassemia intermedia (beta-TI)] were screened for PH defined as tricuspid regurgitant velocity (TRV) >2.5 m/sec and evaluated for PA obstruction using ventilation-perfusion lung scan (V/Q), together with measurement of their plasma levels of NT-pro-BNP. Patients were prospectively followed up for a mean of 18 +/- 6.1 months. The prevalence of PH was 37.5, 40.0 and 26.7% in sickle cell disease, beta-TI and beta-TM patients, respectively. Pulmonary hypertension patients were older, had longer disease duration, higher serum ferritin, serum lactate dehydrogenase (LDH) and NT-pro-BNP with lower hemoglobin (Hb) levels compared to patients without PH. N-terminal pro-BNP was positively correlated with duration of illness, TRV, LDH, serum ferritin, and negatively correlated with Hb levels. The strongest predictor for TRV was serum ferritin followed by the NT-pro-BNP level. Forty-six-point-seven percent of sickle cell disease patients with PH had either high or intermediate probability V/Q scan results compared to 10% of thalassemic patients with PH who had high probability V/Q scan results. Pulmonary hypertension is highly prevalent in young sickle cell disease and thalassemia patients, where elevated serum ferritin and NT-pro-BNP are the main indicators.

Management of CML in the Pediatric Age Group: Imatinib Mesylate or SCT.

BACKGROUND: Management of CML has changed markedly since the introduction of tyrosine kinase inhibitors (TKIs). However stem cell transplantation (SCT) remains a valid therapeutic modality especially in developing countries due to its relatively lower cost. We aim to compare between imatinib mesylate and SCT as regard outcome in CML in the pediatric age group. METHODS: Forty-eight patients with newly diagnosed CML in the chronic phase, aged 3 to 18 years were enrolled in this prospective study. Patients without a matched donor (Group I; N=30) were assigned to receive imatinib mesylate at a dose of 340mg÷m2÷day, while patients with a fully matched related donor (Group II; N=18), were offered SCT. Response (hematologic, cytogenetic and molecular), side effects and survival were analyzed. RESULTS: Complete hematologic response was obtained in 97% of the patients in group I and 94% in group II. Major cytogenetic response (CyR) was obtained in 80% of patients in group I and 100% in group II. Complete CyR was 57% in group I and 64% in group II. Major molecular response (MMR) was 36% in group I and 50% in group II with no significant difference between both groups. Six years overall survival (OS) was 87% in the 1st group and 61% in the 2nd group (p<0.01), while eventfree survival (EFS) was 66% in the 1st group and 50% in the 2nd group with a highly significant difference between both groups (p<0.01). Side effects were generally rare and mild in the imatinib arm, while adverse events were more severe and common in the SCT group (55% had GVHD and 78% had infection). CONCLUSION: Imatinib mesylate has a superior OS and EFS than SCT in children. It is generally safe and well tolerated. Imatinib mesylate should be the 1st line treatment of pediatric patients with CML in the chronic phase. KEY WORDS: CML- Imatinib- SCT- Pediatrics.

Randomized trial of anti-D immunoglobulin versus low-dose intravenous immunoglobulin in the treatment of childhood chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Chronic idiopathic (immune) thrombocytopenic purpura (ITP) develops in approximately 20% of children with acute ITP. Six years ago, low-dose intravenous immunoglobulin (IVIG) treatment of childhood ITP was started at the Pediatric Hematology Unit, Ain Shams University, while intravenous anti-D has been introduced in Egypt in 2001. OBJECTIVES: To assess the efficacy and safety of intravenous anti-D compared to low-dose IVIG in the treatment of children with chronic ITP. PATIENTS AND METHODS: This randomized trial comprised 34 patients with chronic ITP (18 boys and 16 girls) with recurrent bleeding episodes. Median age of the patients was 6.5 years, duration of thrombocytopenia was > 6 months, and platelet count (PC) was < 30 x 10(9)/l (30 K). The patient cohort was divided into two subgroups: group A comprised 18 patients treated with anti-D in a dose of 50 microg/kg i.v. initially, and in 12 of them repeated doses (50 microg/kg) were given every 4 weeks, and group B consisted of 16 children who received IVIG in a dose of 250 mg/kg for 2 consecutive days. Bleeding manifestations, complete blood cell and reticulocyte counts were assessed at baseline and 3, 7, 14 and 28 days after infusion. RESULTS: Clinically, more than 80% of the patients (82.3%) showed good control of bleeding. On day 3, 33.3% of group A versus 37.5% of group B, and on day 7: 66.6% of group A versus 75% of group B patients demonstrated a good response (PC > 50 K and/or doubling of baseline PC). On days 14 and 21, no significant changes in PCs were observed between both groups. However, only 11.1% of group A and 12.5% of group B patients could maintain PC > 100 K on day 28, while 38.8 versus 37.5% of group A and group B, respectively, still had PC > or = double the initial count. The peak response to anti-D was noticed 7 and 14 days following infusion and to IVIG on days 3 and 7. Repeated doses of anti-D could maintain PC > 50 K (or > double the baseline PC) in 75% of patients 1 week after infusion, and in 60% of them by day 28, with good control of bleeding. Splenectomy was postponed and/or avoided in 4 (33.3%) patients on anti-D maintenance therapy who experienced recurrent severe bleeding episodes before starting therapy. The safety of anti-D was judged by the degree of intravascular hemolysis. The mean hemoglobin decrease was 0.8 +/- 0.4 g/dl; in 61.1% of patients the Hb level dropped but none of them experienced a drop of more than 3 g/dl or required transfusion. CONCLUSION: Both single intravenous anti-D and low-dose IVIG effectively increased PC in children with chronic ITP at risk of bleeding or those with previous bleeding episodes. Repeated doses of anti-D could maintain PC above the critical values or double baseline counts in nearly two thirds of the patients showing good control of bleeding and may serve as an alternative to splenectomy in these patients.

5- to 16-year follow-up following splenectomy in chronic immune thrombocytopenic purpura in children.

UNLABELLED: The long-term outcome after splenectomy in children with chronic immune thrombocytopenic purpura (ITP) has not been widely analyzed. We reviewed the medical records of 288 children and adolescents with chronic ITP between 1980 and 1996: 112 were splenectomized; 59 were steroid resistant and 42 were steroid dependent, and 11 were managed with repeated courses of intravenous immunoglobulin (IVIG). All had platelet counts (PCs) <30 x 10(9)/l with frequent bleeding episodes or persistent thrombocytopenia <10 x 10(9)/l. Ninety-eight patients (88%) were evaluated; 58 (60%) patients had never received immunotherapy for ITP following splenectomy. At 5 years, 44 (45%) remained in complete response (CR) and 34 (35%) in partial response (PR). In multivariate analysis, steroid-resistant patients were more likely to relapse after an initial CR (RR 5.2). CONCLUSION: The long-term CR was 45%; 60% had stable PCs >30 x 10(9)/l not requiring therapy. Most postsplenectomy relapses occurred during the 1st year. Initial response to steroids and IVIG prior to splenectomy was a predictor of long-term response to splenectomy.