A comparison of hypersensitivity reactions between intravenous and intramuscular applications of native E. coli asparaginase in children with acute lymphoblastic leukemia.

INTRODUCTION: Asparaginase is an indispensable drug in treating childhood acute lymphoblastic leukemia (ALL). Hypersensitivity reactions (HSR) are the most common side effects and interfere with the antineoplastic activity of the drug. This study aims to compare the intramuscular (IM) and intravenous (IV) administration routes of Native Escherichia coli Lasparaginase (L-ASNase) in terms of hypersensitive reactions. METHODS: L-ASNase was randomly administered IV or IM to newly diagnosed ALL patients and HSR was monitored in all patients for 1 h following the end of the IV infusion and for 2 h following the end of the IM administration of L-ASNase. Based on a retrospective review of clinical charts, reactions were identified. In order to determine the severity of each allergic reaction, we used the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for allergic reactions. RESULTS: A total of 1032 doses of L-ASNase were administered to 85 patients (42 males and 43 females) during the study period. Among 85 patients, 30 reactions were recorded, which means that 35% of the patients reacted. According to the CTCAE, twenty-nine out of 30 reactions (97%) were grade 2, while one (3%) was grade 4. In terms of individual doses, there was a non-significant trend toward increased incidence of reactions with IV administration (3.8% versus 0.9%, p = 0.064). The rate of reactions was higher in patients who received all IV doses (n: 60) as compared to those who received all IM doses (n: 25) (31.7% vs. 3.5%; chi-square= 8.415, p value=0.04). Based on the risk groups and HSR incidence, it was found that high risk group (HRG) patients were significantly more likely to develop HSR compared to the standart risk group (SRG) and intermediate risk group (MRG) patients (chi-square p = 0.003, CI: 95%; odds ratio: 3.12 and 5.91, respectively). CONCLUSIONS: In conclusion, IM administration of L-ASNase causes significantly less HSR to L-ASNase than the IV route. Patients with HRGALL have a higher risk of HSR. Since L-ASNase is still used in many developing countries and there are problems in the supply of Erwinia chrysanthemi ASNase (Erwinia), LASNase can be administered IM to reduce the frequency of HSR.

Improvement in cardiac structure and functions early after transcatheter closure of secundum atrial septal defect in children and adolescents.

We sought to assess the effects of transcatheter closure of atrial septal defect (ASD) on right and left ventricular form and functions, as well as atrial volumes and pulmonary venous flows. We enrolled 25 patients (mean age: 9.02) prospectively who underwent successful transcatheter closure of secundum ASD. We performed transthoracic echocardiography, including two-dimensional, pulsed wave Doppler, M-mode echocardiography, and tissue Doppler imaging before the procedure and 1 day, 1 month, 3 months and 6 months after the procedure. Serum brain natriuretic peptide (BNP) levels were measured prior to the procedure, and 1 day, 1 month, and 3 months there after. Mitral inflow early diastolic wave increased significantly, while isovolumetric relaxation time and deceleration time did not change during the follow-up. The E/E' was also increased significantly during follow-up. After the closure, right ventricular size and right atrial volume reduced, while left ventricular size increased significantly. There was a statistically significant improvement in left and right ventricular Tei indices. Pulmonary vein systolic velocity and the ratio of systolic to diastolic wave decreased, while atrial reversal wave (ARW) velocity increased immediately after the procedure. Although the concentration of BNP was increased on the first day after the procedure, its levels reduced and had reached the pre-procedure values at 1 month of follow-up. In the study, a significant improvement in the right and left ventricular functions was detected after transcatheter closure of secundum ASD in the short-term follow-up. In addition, we found a significant reduction in right heart sizes with corresponding global functional improvement in the right ventricle after the procedure.