Cardio-protective effect of regular transfusion in children with non-transfusion dependent thalassemia (NTDT): A cohort study.

BACKGROUND AND AIM OF THE WORK: Cardiac complications occur in patients with non-transfusion dependent thalassemia (NTDT). The study aimed to evaluate transfusion effect on systolic and diastolic cardiac function in young NTDT patients.  Methods:  Study design: Cohort study. Seventeen regularly-transfused patients with NTDT (12.5±5.3 years; group 1) and 15 none/minimally transfused patients (13.2±4.8 years; group 2) were followed up for 5 years and compared as regards their clinical parameters, echocardiographic and Tissue-Doppler-Imaging. RESULTS: Group 2 patients had significantly higher peak late-diastolic velocity of the left-ventricular-inflow Doppler (Am). Mitral-valve A-wave duration/pulmonary-veins, A-wave duration-ratio and pulmonary-vein S/D velocities-ratio were larger in group 2 as well (p = < 0.01). The diameters of right and left outflow-tract were larger with a higher cardiac-index in patients of group 2. Systolic-function was similar in the 2 studied groups. CONCLUSION: Diastolic function assessment revealed indicators of an abnormal relaxation of left-ventricle in non-transfused patients, which suggests a diastolic dysfunction. An increase in the diameter of the outflow-tract is likely attributed to high cardiac-output status in non-transfused NTDT patients as they have a higher cardiac index. Early start of regular transfusion for NTDT patients might prevent serious long-term cardiac complications.

Low-dose immune tolerance induction therapy in children of Arab descent with severe haemophilia A, high inhibitor titres and poor prognostic factors for immune tolerance induction treatment success.

INTRODUCTION: Immune Tolerance Induction (ITI) is the first-choice therapy to eradicate Factor VIII (FVIII) neutralizing antibodies in patients with haemophilia A (HA). There is limited published data on ITI from East Mediterranean countries. AIM: To assess the effectiveness of a low-dose ITI regimen to eradicate FVIII neutralizing antibodies in children with severe HA and high-titre inhibitors. METHODS: A prospective, single-arm study was conducted in children with HA (FVIII < 1 IU/dl), high-titre inhibitors and poor prognostic factors for successful ITI. Patients were treated with ∼50 IU/kg plasma-derived FVIII containing von Willebrand factor (pdFVIII/VWF) concentrate (Koate-DVI, Grifols) three times a week. Time to achieve tolerance, total and partial success were analysed after ITI. Annual bleeding rate (ABR), number of target joints, FVIII recovery and school absence were compared before and after ITI. RESULTS: Twenty patients with median (range) age of 6.2 (3-12) years and pre-ITI inhibitor titre of 36.5 (12-169) BU were enrolled. ITI lasted ≤12 months (early tolerization) in 45% of patients. Median follow-up was 12 months (3-22) and total response rate was 80% (60% total success; 20% partial success). Patients with two and three poor prognosis factors achieved overall success rate of 60% and 50%, respectively. ABR, target joints and school absence were reduced after ITI by 60%, 50% and 44.1%, respectively. In successful ITI tolerized patients, FVIII recovery was 90 (60-100)%. CONCLUSION: A low-dose ITI therapy using a pdFVIII/VWF concentrate achieved at least partial tolerance in 80% of patients, and reduced annual bleeds in children with high inhibitor titres and at least one poor prognosis factor for ITI treatment success.

Management of children with glucose-6-phosphate dehydrogenase deficiency presenting with acute haemolytic crisis during the SARs-COV-2 pandemic.

BACKGROUND AND OBJECTIVES: Shortage of blood during the severe acute respiratory syndrome-COV-2 (SARs-COV-2) pandemic impacted transfusion practice. The primary aim of the study is to assess management of acute haemolytic crisis (AHC) in glucose-6-phosphate dehydrogenase(G6PD)- deficient children during SARs-COV-2 pandemic, and then to assess blood donation situation and the role of telemedicine in management. METHODS: Assessment of G6PD-deficient children attending the Emergency Department (ER) with AHC from 1 March 2020 for 5 months in comparison to same period in the previous 2 years, in three paediatric haematology centres. AHC cases presenting with infection were tested for SARs-COV-2 using RT-PCR. Children with Hb (50-65 g/L) and who were not transfused, were followed up using telemedicine with Hb re-checked in 24 h. RESULTS: A 45% drop in ER visits due to G6PD deficiency-related AHC during SARs-COV-2 pandemic in comparison to the previous 2 years was observed. 10% of patients presented with fever and all tested negative for COVID-19 by RT-PCR. 33% of patients had Hb < 50 g/L and were all transfused. 50% had Hb between 50 and 65 g/L, half of them (n = 49) did not receive transfusion and only two patients (4%) required transfusion upon follow up. A restrictive transfusion strategy was adopted and one of the reasons was a 39% drop in blood donation in participating centres. CONCLUSION: Fewer G6PD-deficient children with AHC visited the ER during SARs-COV-2 and most tolerated lower Hb levels. Telemedicine was an efficient tool to support their families. A restrictive transfusion strategy was clear in this study.

Preoperative transfusion versus no transfusion policy in sickle cell disease patients: a randomized trial.

BACKGROUND: Many children with sickle cell disease (SCD) indicated for adenotonsillectomy receive pre-operative transfusion therapy, either simple or exchange transfusion, in order to reduce surgical and sickle cell disease-related complications. SUBJECTS AND METHODS: This is a prospective randomized controlled clinical trial aiming to compare between preoperative simple transfusion and no transfusion in pediatric patients with sickle SCD admitted in Sultan Qaboos University Hospital, Muscat, Oman for adenotonsillectomy during the period from January 2014 through June 2018. They were randomly assigned into two arms (simple transfusion and no transfusion). RESULTS: Postoperative SCD-related complications have been encountered in 6 out of 138 patients (4.3%). There was no statistically significant difference between the two studied groups as regards the development of surgical or SCD-related complications (p = 0.6 and 0.8 respectively). The length of postoperative hospital stay was comparable in the two groups. (p = 0.607). SCD-related complications occurred exclusively in cases with homozygous sickle anemia (4 out of 81 = 4.9%). CONCLUSION: Sickle cell disease patients with a hemoglobin level above 7.5 g/dL do not need PRBCs transfusion prior to adenotonsillectomy. This approach did not increase the risk of postoperative surgical or SCD-related complications.

Renal iron deposition by magnetic resonance imaging in pediatric ß-thalassemia major patients: Relation to renal biomarkers, total body iron and chelation therapy.

BACKGROUND: The reciprocal of multiecho gradient-echo (ME-GRE) T2* magnetic resonance imaging (MRI) R2*, rises linearly with tissue iron concentration in both heart and liver. Little is known about renal iron deposition in ß-thalassemia major (ß-TM). AIM: To assess renal iron overload by MRI and its relation to total body iron and renal function among 50 pediatric patients with ß-TM. METHODS: Serum ferritin, serum cystatin C, urinary albumin creatinine ratio (UACR), and urinary ß2-microglobulin (ß2 M) were measured with calculation of ß2 M/albumin ratio. Quantification of liver, heart and kidney iron overload was done by MRI. RESULTS: Serum cystatin C, UACR and urinary ß2 microglobulin as well as urinary ß2m/albumin were significantly higher in ß-TM patients than the control group. No significant difference was found as regards renal R2* between Patients with mean serum ferritin above 2500 µg/L and those with lower serum cutoff. Renal R2* was higher in patients with poor compliance to chelation therapy and positively correlated to indirect bilirubin, LDH, cystatin C and LIC but inversely correlated to cardiac T2*. CONCLUSION: kidney iron deposition impairs renal glomerular and tubular functions in pediatric patients with ß-TM and is related to hemolysis, total body iron overload and poor compliance to chelation.

A randomized multicenter study: safety and efficacy of mini-pool intravenous immunoglobulin versus standard immunoglobulin in children aged 1-18 years with immune thrombocytopenia.

BACKGROUND: Because there is a global shortage of intravenous immunoglobulin, there is a need for new products to fill the gap. STUDY DESIGN AND METHODS: This was a multicenter, open-label study investigating the safety and efficacy of a newly developed mini-pool intravenous immunoglobulin G for children with immune thrombocytopenia. Seventy-two patients ages 1 to 18 years with newly diagnosed (<1 month) immune thrombocytopenia who had platelet counts from 5 to 20 × 109 /L with no serious bleeding were recruited from four centers in Egypt. Eligible patients were randomized into three groups 1:1:1. Group A (n = 24) received blood group-specific mini-pool intravenous immunoglobulin in a dose equivalent to immunoglobulin 1 g/kg over 6 to 8 hours, Group B (n = 24) received standard intravenous immunoglobulin (approximately 1g/kg) as a single dose, and Group C (n = 24) did not receive any platelet-enhancing therapy. Parents signed informed consent. RESULTS: Of the patients who received mini-pool intravenous immunoglobulin, 14 achieved a complete response (CR) (58.8%), and four had a response (16.6%). Of the patients who received intravenous immunoglobulin G, 16 achieved a complete response (66.6%), and four had a response (16.6%). In Group C, eight patients achieved a complete response (33.3%), and four had a response (16.6%). The median time to response was 8, 9, and 21 days in Group A, B, and C, respectively, which was significantly higher in Group C than Groups A and B (p < 0.001). Patients in Groups A and B reported 16 adverse drug reactions. CONCLUSION: Mini-pool intravenous immunoglobulin G was well tolerated, presented no safety issues, and was effective in the treatment of immune thrombocytopenia, with efficacy comparable to that of the standard intravenous immunoglobulin G group, and it was significantly more effective than no treatment.

Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young ß-thalassemia intermedia patients.

OBJECTIVE: To assess the efficacy and safety of combined hydroxyurea (HU) and recombinant human erythropoietin (rHuEPO) in ß-thalassemia intermedia (TI) patients compared with single HU therapy. METHODS: An interventional prospective randomized study registered in the ClinicalTrials.gov (NCT01624038) was performed on 80 TI patients (≤ 18 yr) divided into group A (40 patients received combined HU and rHuEPO) and group B (40 patients received single HU therapy). Baseline serum EPO levels were measured, and both groups were followed up for a mean period of 1 yr with regular assessment of transfusion requirements, blood pressure, ferritin, liver and renal functions, hemoglobin, and HbF. Quality of life (QoL) was assessed at the start and end of the study. RESULTS: Transfusion frequency and index were significantly decreased, while QoL was increased in group A compared with group B where 85% of patients showed improvement on combined therapy compared with 50% of patients on HU. Hemoglobin and HbF were significantly increased in both TI groups; however, this was more evident in group A than in group B. Also, 37.5% of patients in group A became transfusion-independent compared with 15% in group B. EPO levels were negatively related to increments of hemoglobin and HbF. Splenectomized patients and those with initial HbF% >40% had the best response to combined therapy. No serious adverse events necessitating discontinuation of therapy in both groups. CONCLUSIONS: HU was effective in management of TI; however, combination with rHuEPO gave a superior therapeutic effect resulting in the best clinical and hematological responses without adverse events.