Eltrombopag in pediatric chronic and refractory ITP: data from a retrospective multicenter study from Lebanon.

About 20% to 30% of pediatric patients with immune thrombocytopenia (ITP) develop chronic or refractory disease lasting 12 months or more that can be challenging to treat. Eltrombopag is being used after failure of previous lines of therapy with good results at tertiary healthcare centers in Lebanon, a developing country with available multidisciplinary treatment modalities. This is a retrospective multicenter observational study that analyzed data on pediatric patients with chronic or refractory ITP who were given eltrombopag as second- or third-line therapy in 6 large referral hospitals in Beirut (country capital located in mid Lebanon), South, North, and Mount Lebanon between October 2016 and May 2020. The primary end point of the study was a proportion of patients achieving platelet counts of ≥ 50 × 109/L for at least 6 weeks without requiring rescue therapy during the observation period. Data from 36 patients treated for chronic and refractory ITP, 20 (55.6%) males and 16 (44.4%) females, were analyzed. The median age at the eltrombopag dose was 11 years (2-18 years). All the patients had failure of the first-line therapy with steroids, 3 patients received eltrombopag as second-line therapy, and the remaining patients had failure of at least 2 previous lines of therapy, including steroids. The primary end point was achieved in 21 (58.3%) of 36 patients. The treatment was discontinued in 3 patients due to no response. Hepatotoxicity and all other adverse events (headache, weakness, and diarrhea) were mild and transient. All the patients who achieved the target platelet count of ≥ 50 × 109/L maintained the response for the treatment duration, which was a minimum of 5 months up to 3 years, with median/mean observation periods of 12 months and 14 months, respectively. This study confirms the findings of randomized controlled trials that eltrombopag as second- or third-line therapy in pediatric patients with chronic and refractory ITP is effective and safe, reinforcing its role in the real-world management of these patients.

DNMT3B deficiency presenting as severe combined immune deficiency: A case report.

Immunodeficiency, Centromeric instability and Facial anomalies (ICF) syndrome is a group of rare autosomal recessive disorders. The immune disease in the ICF syndrome consists mainly of humoral immunodeficiency. T-cell dysfunction has previously been suspected to be part of the syndrome's spectrum. However, patients with ICF display, at a young age, a normal number of T cells that tend to decline throughout disease progression due to apoptosis. Biallelic mutations in the DNMT3B gene account for around 50% of ICF cases (ICF type 1). The remaining half may be linked to ZBTB24, CDCA7 or HELLS. Here we report a novel homozygous DNMT3B mutation (NM_ 006892; p.R826H) in a Lebanese family presenting in early infancy with severe combined immune deficiency (SCID). This work expands the clinical spectrum of the ICF syndrome and confirms the importance of tailoring therapeutic approaches for each patient with ICF syndrome, according to the clinical manifestations of his disease.

Spontaneous splenic rupture in a patient with factor XIII deficiency and a novel mutation.

We report a novel mutation in factor XIIIA gene that caused severe congenital factor XIII deficiency in a 6 year and 8 month old male. The mutation is a GA deletion in the core domain leading to a premature stop at codon 502. The child had severe deficiency with two episodes of intracerebral hemorrhage. He also developed spontaneous splenic rupture, an unusual complication of this disorder.

Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial.

BACKGROUND: Despite the high prevalence of hypovitaminosis D in children and adolescents worldwide, the impact of vitamin D deficiency on skeletal health is unclear. METHODS: One hundred seventy-nine girls, ages 10-17 yr, were randomly assigned to receive weekly oral vitamin D doses of 1,400 IU (equivalent to 200 IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in a double-blind, placebo-controlled, 1-yr protocol. Areal bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine, hip, forearm, total body, and body composition were measured at baseline and 1 yr. Serum calcium, phosphorus, alkaline phosphatase, and vitamin D metabolites were measured during the study. RESULTS: In the overall group of girls, lean mass increased significantly in both treatment groups (P < or = 0.05); bone area and total hip BMC increased in the high-dose group (P < 0.02). In premenarcheal girls, lean mass increased significantly in both treatment groups, and there were consistent trends for increments in BMD and/or BMC at several skeletal sites, reaching significance at lumbar spine BMD in the low-dose group and at the trochanter BMC in both treatment groups. There was no significant change in lean mass, BMD, or BMC in postmenarcheal girls. CONCLUSIONS: Vitamin D replacement had a positive impact on musculoskeletal parameters in girls, especially during the premenarcheal period.

Sex differences in the effect of body-composition variables on bone mass in healthy children and adolescents.

BACKGROUND: Prophylactic interventions against osteoporosis require a determination of the factors that influence the accumulation of bone mass during growth. OBJECTIVE: The objective was to determine the independent sex-specific contribution of lean mass and fat mass to bone mineral content (BMC), after adjustment for anthropometric variables and lifestyle factors, in healthy children and adolescents. DESIGN: Healthy schoolchildren (184 boys and 179 girls) aged 10-17 y (x+/- SD: 13.0 +/- 2.1 y) participated in this cross-sectional study. Total and regional (lumbar spine, femoral neck, and distal one-third of the radius) BMC and body composition were measured by dual-energy X-ray absorptiometry. RESULTS: A significant effect of anthropometric variables and lifestyle factors on BMC was observed at all skeletal sites. Lean mass and fat mass showed robust correlations with BMC, even after adjustment for anthropometric variables and lifestyle factors. Lean mass contributed to 6-12% of the variance in BMC in boys and to 4-10% in girls. Fat mass accounted for 0.1-2% of BMC variance in boys and to 0.1-6.5% in girls. CONCLUSIONS: Both lean mass and fat mass are consistent predictors of BMC at multiple skeletal sites in healthy children and adolescents. The contribution of lean mass to BMC variance was larger in boys than in girls. In both sexes, the highest contribution of lean mass to BMC was observed at the femoral neck.

Bone mineral density by age, gender, pubertal stages, and socioeconomic status in healthy Lebanese children and adolescents.

Gender, ethnicity, and lifestyle factors affect bone mass acquisition during childhood, thus the need for age- and sex-adjusted Z scores using ethnic-specific data for bone mineral density (BMD) measurement. This study aimed at establishing normative data for BMD in healthy Lebanese children and adolescents. Three hundred sixty-three healthy children aged 10 to 17 years (mean+/-SD: 13.1+/-2.0) were studied. BMD, bone mineral content (BMC), and lean mass were measured by dual-energy X-ray absorptiometry (DXA) using a Hologic 4500A device, and apparent volumetric BMD (BMAD) of the lumbar spine and the femoral neck were calculated. BMD, BMC, and BMAD were expressed by age groups and Tanner stages for boys and girls separately. There was a significant effect of age and puberty on all bone parameters, except at the femoral neck BMAD in boys. BMC and BMD were higher at cortical sites in boys, including subtotal body and hip; whereas, in girls, it was higher at a site more enriched in trabecular bone, namely the lumbar spine. At several skeletal sites, girls had significantly higher BMD adjusted for lean mass than boys. By the end of puberty, adolescents had a mean BMD that was 43-66% higher at the lumbar spine and 25-41% higher at cortical sites than pre-pubertal children, depending on the gender. Mean BMD values in the study group were significantly lower (P<0.01) than Western normative values, with Z scores ranging between -0.2 and -1.1. In both genders, children of lower socioeconomic status tended to have lower BMD than those from a higher socioeconomic background. This study allows additional insight into gender dimorphism in mineral accretion during puberty. It also provides a valuable reference database for the assessment of BMD in children with pubertal or growth disorders who are of Middle Eastern origin.