Is FLT3 internal tandem duplication an unfavorable risk factor for high risk children with acute myeloid leukemia? : Polish experience

According to the AML-BFM 2004 Interim, a treatment protocol used in Poland since 2005, presence of FLT3 internal tandem duplication (FLT3/ITD) qualifies a patient with acute myeloid leukemia (AML) to a high-risk group (HRG). The present study was aimed to identify the prevalence of FLT3/ITD in children with AML in Poland and to evaluate its prognostic significance in the HRG patients. Out of 291 children with de novo AML treated in 14 Polish centers between January 2006 and December 2012, samples from 174 patients were available for FLT3/ITD analysis. Among study patients 108 children (61.7%) were qualified to HRG. Genomic DNA samples from bone marrow were tested for identification of FLT3/ITD mutation by PCR amplification of exon 14 and 15 of FLT3 gene. Clinical features and treatment outcome in patients with and without FLT3/ITD were analyzed in the study. The FLT3/ITD was found in 14 (12.9%) of 108 HRG children. There were no significant differences between children with and without FLT3/ITD in age and FAB distribution. The white blood cells count in peripheral blood at diagnosis was significantly higher (p <0.01) in the children with FLT3/ITD. Over 5-year overall survival rate for FLT3/ITD positive children was worse (42.4%) comparing to FLT3/ITD negative children (58.9%), but the statistical difference was not significant. However, over 5-year survivals free from treatment failures were similar. The FLT3/ITD rate (12.9%) observed in the study corresponded to the published data. There was no significant impact of FLT3/ITD mutation on survival rates, although further studies are needed on this subject

Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

Background: Activated phosphoinositide-3-kinase d syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. Objectives: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain of-function (GOF) disease; and identify predictors of severity in APDS. Methods: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. Results: The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. Conclusions: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients. (J Allergy Clin Immunol 2023;152:984-96.

The effect of clomiphene citrate on osteoporosis in ovariectomized rats

PubMed ID: 18193254Objective: The aim of this study was to investigate whether clomiphene citrate (CC) administration could be a new therapeutic agent in case of contraindication of estrogen therapy for hormone-dependent osteoporosis and to show the changes in bone structure by histomorphometric analysis in ovariectomized rats administered CC. Study design: This study was carried out in the Experimental Surgery Laboratory of the Brain Research Centre of the Medical Faculty of Ege University. Four-month-old Sprague-Dawley rats were used for the experiment. The study was carried out on six groups of animals each consisted of eight rats. Four groups of rats were ovariectomized and 2 groups of rats were used as control group. For 6 weeks every day, rats were injected physiological saline solution (1 ml/kg), clomiphene citrate (1 or 10 mg/1 ml/kg, Organon), 17ß-estradiol (50 µg/1 ml/kg, within susame oil, Sigma) or susame oil (1 ml/kg, Sigma). Drug administrations were carried out according to the weekly weight measurements. Group 1(PSS), n = 8, non-ovariectomized, were injected with physiological saline solution. Group 2(CC-1), n = 7, non-ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 3(OVX + CC-1), n = 7, ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 4(OVX + CC-10), n = 6, ovariectomized, were injected with CC (10 mg/1 ml/kg). Group 5(OVX + E), n = 8, ovariectomized, were injected with 17ß-estradiol (50 µg/1 ml/kg). Group 6(OVX), n = 8, ovariectomized, were injected with susame oil (1 ml/kg) Bone-specific serum alkaline phosphatase (ALP) levels were measured and statistical analyses were made by Kruskal Wallis test. Left femur bone histomorphometric studies were done. The uteri were dissected out to measure their weight and ANOVA was used to show the intergroup differences. Results: The level of ALP in group 3 was significantly higher than the other five groups. Bone histomorphometric examination showed that total bone volume in group 3, 4, and 5 was higher than group 6, and group 4 had the highest level of bone volume compared to the rest of the groups. Uterus weights in group 1 were significantly higher than group 3 and 6 (P = 0.02, P = 0.01) and uterus weights in group 5 were significantly higher than group 3 and 4 (P = 0.00, P = 0.01) Conclusions: In ovariectomized rats, treatment with CC is seen as effective as estrogen treatment in preventing osteoporosis, without causing uterin hyperstimulation. Nevertheless, further investigations on more rats are needed to assess whether it is an alternative treatment method to estrogen. © 2007 Springer-Verlag

Assessment of hepatitis B immunization status after antineoplastic therapy in children with cancer

BACKGROUND AND OBJECTIVES: Hepatitis B is a disease that is preventable with vaccination. Antibody levels after vaccination may be affected by suppression of the immune system due to cancer therapy. Children with cancer have a high risk of hepatitis B virus (HBV) infection. We aimed to assess the pretreatment immunization status against HBV infection and the rate of continuity of immunization after therapy in children with cancer