Baseline CD3+CD56+ (NKT-like) Cells and the Outcome of Influenza Vaccination in Children Undergoing Chemotherapy.

Background: In children undergoing chemotherapy yearly influenza vaccination is recommended by treatment protocols. We investigated the relationship between cellular immunity and the antibody response to inactivated influenza vaccines. Methods: 25 patients (age: 2-18 years) undergoing chemotherapy for different malignancies participated in our study. Flow cytometric detection of peripheral blood lymphocyte subpopulations together with hemagglutination inhibition antibody titers were measured before and 21-28 days after vaccination. We examined the ratio and total numbers of CD3+, CD4+, CD8+ T cells, activated helper (CD3+CD4+CD25low), regulatory (CD3+CD4+CD25high), naive (CD3+CD45RA+) and memory (CD3+CD45RO+) T cells, CD56+NK, and CD3+CD56+ (NKT-like) cells. Relationships between specific antibody responses (seroprotection, seroconversion, geometric mean titer (GMT), geometric mean fold increase (GMFI)) and the ratios and counts of lymphocyte subpopulations were evaluated using one-way ANOVA and the paired sample t test after dichotomization according to age-related reference values. Results: Patients with CD4+ lymphocyte levels in the normal age-specific range showed significantly better response regarding postvaccination GMT elevation for H1N1 and H3N2 strains (97.52 vs. 19.2, p=0.019, 80 vs. 14.43, p=0.021, respectively). GMFI results were significant only against B strain (2.69-fold vs. 1.23-fold, p=0.046). Prevaccination CD3+CD56+ (NKT-like) cells above predicted values according to age showed significant associations both in postvaccination GMT elevation (H1N1: 75.11 vs. 14.14, p=0.010; H3N2: 62.18 vs. 11.22, p=0.012; B: 22.69 vs. 6.67, p=0.043) and GMFI against all three strains (H1N1: 3.76-fold vs. 1.06-fold, p=0.015; H3N2: 2.74-fold vs. 1, p=0.013; B: 2.57-fold vs. 1, p=0.008). By one-way ANOVA, we found a positive relation between absolute lymphocyte cell count above 1000/µl and the postvaccination GMT elevation against H3N2 (12.81 vs. 56.56, p=0.032), and GMFI regarding H1N1 (1.22-fold vs. 3.48-fold, p=0.044). Conclusions: In addition to verifying the predictive value of absolute lymphocyte count above 1000/µl, our results suggest an association between NKT-like cell counts and the specific antibody response against all three investigated influenza strains in highly immunosuppressed patients. Furthermore, prevaccination CD4+ lymphocyte levels in the normal age-specific range may influence seroresponse.

Pharmacogenetics of the Central Nervous System-Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia.

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations' matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.

Assessment of the results and hematological side effects of 3D conformal and IMRT/ARC therapies delivered during craniospinal irradiation of childhood tumors with a follow-up period of five years.

BACKGROUND: Craniospinal irradiation (CSI) of childhood tumors with the RapidArc technique is a new method of treatment. Our objective was to compare the acute hematological toxicity pattern during 3D conformal radiotherapy with the application of the novel technique. METHODS: Data from patients treated between 2007 and 2014 were collected, and seven patients were identified in both treatment groups. After establishing a general linear model, acute blood toxicity results were obtained using SPSS software. Furthermore, the exposure dose of the organs at risk was compared. Patients were followed for a minimum of 5 years, and progression-free survival and overall survival data were assessed. RESULTS: After assessment of the laboratory parameters in the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side effects during the IMRT/ARC and 3D conformal treatments. Laboratory parameters decreased significantly compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival or overall survival, and no signs of serious organ toxicity due to irradiation were observed during the follow-up period in either of the groups. CONCLUSION: The RapidArc technique can be used safely even in the treatment of childhood tumors, as the extent of the exposure dose in normal tissues and the amount of acute hematological side effects are not higher with this technique.

Urothelial Papilloma of the Urinary Bladder in Children: Report of Two Cases.

Urothelial neoplasms of the bladder (UNB) are considerably rare throughout the pediatric population. UNB develops from the urothelial tissue in the form of a benign disease, generally favoring a successful prognosis in the majority of cases. The authors present the diagnosis and treatment regarding two medical case reports in which urothelial papilloma was diagnosed and effectively treated. Case 1 : A 15-year-old male patient was presented to our clinic complaining of a painless yet distinctive, macroscopic form of hematuria. Following a routine examination, which included ultrasound (US) and intravenous pyelography, the urethrocystoscopy revealed an intravesical solitary lesion positioned in the vicinity of the left ureteral orifice. Additionally, histology confirmed urothelial papilloma. During the follow-up, laboratory, urinary control tests, and US results all proved negative. Case 2 : A 13-year-old male patient was admitted to our clinic and examined, in regard to complaints associated with recurrent abdominal pain. The pathology was discovered incidentally on abdominal US. Preoperative US and magnetic resonance imaging (MRI) studies ensued, resulting in a scheduled MRI, followed by urethrocystoscopy, which confirmed an intravesical solitary lesion positioned near the right ureteral orifice. Histology revealed urothelial papilloma. During the follow-up control cystoscopy, one resection was repeated due to the presence of a residual tumor. Today, 10 years since the presence of uroepithelial papilloma, both patients are asymptomatic and tumor-free. If there is likely suspicion of recurrence, cystoscopy is recommended.

Chondromesenchymal Hamartoma in Ectopic Thyroid Tissue in a Neonate.

A full-term male neonate presented with a left sided cervical lump at the level of the thyroid gland. Magnetic resonance imaging (MRI) showed a benign heterogeneous solid mass with lobulated margins. The tumor underwent complete excision. Histology revealed the diagnosis of chondromesenchymal hamartoma in ectopic thyroid tissue.