Association of CEP72 rs924607 TT Genotype with Vincristine-induced Peripheral Neuropathy Measured by Motor Nerve Conduction Studies.

Vincristine is at the core of many treatment protocols for childhood malignancies. The major dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN) which may cause morbidity and disrupt curative treatment. Several studies have tried to identify pharmacogenetic biomarkers for susceptibility to vincristine-induced toxicity (Egbelakin A et al., Pediatr Blood Cancer 2011; 56: 361-367. Aplenc R et al., Br J Haematol 2003; 122: 240-244. Diouf B et al., JAMA 2015; 313: 815-823. Zgheib NK et al., Pharmacogenet Genomics, 2018; 28: 189-195. Gutierrez-Camino A et al., Pharmacogenet Genomics 2016; 26: 100-102. Wright GE et al., Clin Pharmacol Ther 2019; 105: 402-410. Kayilioglu H et al., J Pediatr Hematol Oncol 2017; 39(6): 458-462). A major limitation of these studies is that VIPN is difficult to measure objectively using only clinical examination and clinical scales. This is especially true for children, who are often unable to report or grade symptoms such as paresthesia, numbness, and pain. Furthermore, some studies are questioning the validity of currently available neuropathy grading scales (Postma TJ et al., Ann Oncol 1998; 9: 739-744). Our group recently showed that electrophysiological studies can be used with great accuracy for early detection of VIPN (Kavcic M et al., J Pediatr Hematol Oncol 2017; 39: 266-271). In the previous study, we found that VIPN presents with primary axonal involvement and is more pronounced on motor neurons (Kavcic M et al., J Pediatr Hematol Oncol 2017; 39: 266-271).

Parvovirus B19-associated Hemophagocytic Lymphohistiocytosis in a Patient With Glucose-6-phosphate Dehydrogenase Deficiency.

We report a case of a 12-year-old male with glucose-6-phosphate dehydrogenase deficiency presenting with clinical signs of sepsis and pancytopenia. Investigations revealed parvovirus B19 (PVB19)-associated hemophagocytic lymphohistiocytosis (HLH). The patient recovered fully and quickly with symptomatic treatment. Current evidence suggests that PVB19-associated HLH has a favorable prognosis. Mild undiagnosed cases of HLH may be the cause of pancytopenia in PVB19 infections.

Pediatric-Inspired Regimens in the Treatment of Acute Lymphoblastic Leukemia in Adolescents and Young Adults: A Systematic Review.

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have significantly worse outcomes than their younger counterparts. Current treatment guidelines rely mostly on non-randomized retrospective studies. We performed a systematic review of studies published within the last 15 years comparing pediatric-inspired regimens (PIR) versus adult-type regimens or performing an age-stratified analysis of outcomes in the AYA population. Due to the heterogeneity of data, a meta-analysis was not possible. However, the gathered data show a trend toward improvement in outcomes and an acceptable toxicity profile in patients treated with PIRs compared to conventional adult-type regimens. There is still room for further improvement, as older patients within the AYA population tend to perform poorly with PIR or conventional adult-type chemotherapy. Further randomized studies are needed to develop an optimal treatment strategy for AYA with ALL.

Micronized, Microencapsulated Ferric Iron Supplementation in the Form of >Your< Iron Syrup Improves Hemoglobin and Ferritin Levels in Iron-Deficient Children: Double-Blind, Randomized Clinical Study of Efficacy and Safety.

A major problem of oral iron supplementation efficacy in children is its tolerability and compliance. We aimed to determine the safety and efficacy of a novel food supplement >Your< Iron Syrup in the replenishment of iron stores and improvement of hematological parameters in iron-deficient children aged nine months to six years. We randomized 94 healthy children with iron deficiency in a ratio of 3:1 to either receive >Your< Iron Syrup or placebo. A 12-week supplementation with >Your< Iron Syrup resulted in a significant increase in ferritin and hemoglobin levels as compared to placebo (p = 0.04 and p = 0.02). Adverse events were reported with similar frequencies across both study arms. >Your< Iron Syrup represents an effective, well-tolerated, and safe option for the management of nutritional iron deficiency in children.

Potential protective role of a NOD2 polymorphism in the susceptibility to multiple sclerosis is not associated with interferon therapy.

Pattern recognition receptors, such as specific nucleotide-binding oligomerization domain protein 2, and their polymorphisms may be involved in the pathogenesis of multiple sclerosis (MS). They may also play a role in the formation of neutralizing antibodies against interferon-ß (INF-ß), and may exhibit lowered efficacy. Identification of these polymorphisms may be useful for early identification of potential non-responders and to allow for modification of treatment regimens earlier. The differences in genotype distribution and allele frequency of the rs3135499 and rs2066842 NOD2 polymorphisms between patients with MS and healthy controls were analysed in the present study. The group of patients were divided into responders and non-responders to INF-ß therapy to evaluate the association of both polymorphisms with response to therapy. No differences in the genotype frequencies between the responder and non-responder groups were observed. However, a statistically significant difference in genotype frequencies of TT homozygotes for rs2066842 between patients with MS and healthy controls was observed (χ2=11.8; P=0.003). A recessive genotype model and allele distribution in rs2066842 suggest that the genotype TT and allele T itself are protective against MS. The odds ratio of 0.12 represents an 8.33x lower risk for MS if an individual has a TT genotype. The significantly lower incidence of the TT genotype of rs2066842 in patients with MS suggests that the TT genotype and T allele may be a protective genetic factor against MS.

Centrosomal protein72 rs924607 and vincristine-induced neuropathy in pediatric acute lymphocytic leukemia: meta-analysis.

AIM: We examined the utility of the rs924607 TT genotype of the centrosomal protein 72 (CEP72) as a potential biomarker for predilection toward vincristine-induced peripheral neuropathy in children treated for acute lymphoblastic leukemia. MATERIALS & METHODS: We conducted a random-effects meta-analysis of data from four studies comprising 817 patients. We tested for an association using a recessive model where a one-sided p-value < 0.05 was considered statistically significant. RESULTS & CONCLUSION: We were unable to confirm the association between the rs924607 TT genotype and neurotoxicity (odds ratio: 1.99; p = 0.16; 95% CI: 0.76-5.25) in our global meta-analysis. Analysis of the continuation phase (following induction) studies showed significantly higher odds for neuropathy in CEP72 rs924607 TT homozygotes (odds ratio: 2.28; p = 0.02; 95% CI: 1.16-6.87).