Assessment of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Multicenter Study From Turkey.

Assestment of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) is of utmost importance both for risk classification and tailoring of the therapy. The data of pediatric ALL patients that received treatment with Berlin-Frankfurt-Münster (BFM) protocols were retrospectively collected from 5 university hospitals in Turkey. Of the 1388 patients enrolled in the study 390 were treated according to MRD-based protocols. MRD assestment was with real time quantitative polymerase chain reaction (qPCR) in 283 patients and with multiparametric flow cytometry (MFC)-MRD in 107 patients. MRD monitoring had upstaged a total of 8 patients (2%) from intermediate risk group to high-risk group. Univariate analysis revealed age 10 years or above, prednisone poor response, PCR-MRD ≥10-3 on day 33 and on day 78 as poor prognostic factors affecting event-free survival (EFS). Detection of >10% blasts on day 15 with MFC (MFC-high-risk group) was not shown to affect EFS and/or overall survival (log-rank P=0.339). Multiple logistic regression analysis revealed PCR-MRD ≥10-3 on day 78 as the only poor prognostic factor affecting EFS (odds ratio: 8.03; 95% confidence interval: 2.5-25; P=0.000). It is very important to establish the infrastructure and ensure necessary standardization for both MRD methods for optimal management of children with ALL.

Dinutuximab beta plus conventional chemotherapy for relapsed/refractory high-risk neuroblastoma: A single-center experience.

Background: Relapsed/refractory high-risk neuroblastoma has a dismal prognosis. Anti-GD2-mediated chemo-immunotherapy has a notable anti-tumor activity in patients with relapsed/refractory high-risk neuroblastoma. The purpose of this study was to analyze the efficacy and safety of the combination of immunotherapy with dinutuximab beta (DB) and chemotherapy in patients with relapsed/refractory high-risk neuroblastoma. Methods: All patients received the Turkish Pediatric Oncology Group NB 2009 national protocol for HR-NB treatment at the time of diagnosis. Salvage treatments were administered after progression or relapse. The patients who could not achieve remission in primary or metastatic sites were included in the study. The most common chemotherapy scheme was irinotecan and temozolomide. DB was administered intravenously for 10 days through continuous infusion with 10 mg/m2 per day. The patients received 2 to 14 successive cycles with duration of 28 days each. Disease assessment was performed after cycles 2, 4, and 6 and every 2 to 3 cycles thereafter. Results: Between January 2020 and March 2022, nineteen patients received a total of 125 cycles of DB and chemotherapy. Objective responses were achieved in 12/19 (63%) patients, including complete remission in 6/19 and partial response in 6/19. Stable disease was observed in two patients. The remaining five patients developed bone/bone marrow and soft tissue progression after 2-4 cycles of treatment. The most common Grade ≥3 toxicities were leukopenia, thrombocytopenia, hypertransaminasemia, fever, rash/itching and capillary leak syndrome, respectively. Conclusion: Our study results suggest that DB-based chemo-immunotherapy seems to be suitable with encouraging response rates in patients with relapsed/refractory high-risk neuroblastoma.

Investigating the risk factors for antibiotic lock therapy failure in pediatric cancer: a single center retrospective analysis.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is one of the most common complications of central lines. Data concerning the effectiveness and safety of antibiotic lock therapy (ALT), especially in pediatric hematology and oncology patients, have not yet reached sufficient levels of evidence. We aimed to share our center`s experience on ALT in pediatric cancer and to investigate the causes of ALT failure. METHODS: All cases with CRBSI and treated with ALT administiration in children with cancer between January 2015 and May 2019 were reviewed. Patients characteristics, laboratory and clinical findings, treatments, outcome of ALT, recurrences and reinfections were recorded. Patients with successful and unsuccessful ALT outcomes were compared in order to identify the risk factors for ALT failure. RESULTS: Sixteen eligible CRBSI treated with adjunctive ALT were identified. The most common pathogens were coagulase negative staphylococci (8/16, 50%). Treatment failure was observed in 31.2% (5/16). Younger age alone was an independent risk factor for treatment failure (0.9 vs 6.8 years, p = 0.038). Recurrence and reinfection rates were 23.1% and 16.7%. Mild bleeding occured in two cases (12.5%) and occlusion causing catheter removal was seen in one (6.3%). CONCLUSIONS: ALT was found to be a safe modality with a success rate of 68.8% in children with cancer at our center and younger age was an independent risk factor for treatment failure. Future studies with larger sample sizes are needed to determine the factors affecting the ALT outcome, especially in childhood malignancies.

Frequency of Celiac Disease and Spontaneous Normalization Rate of Celiac Serology in Children and Adolescent Patients with Type 1 Diabetes

Objective: The prevalence of celiac disease (CD) varies between 1% and 10% in patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the frequency of spontaneous recovery of celiac serology and the biopsy-proven CD (BPCD) frequency in patients with T1DM. Methods: The data of 668 patients with available celiac serology tests from a total of 779 patients who were followed for the last 10 years with the diagnosis of T1DM were retrospectively evaluated. Results: Positive serology was detected in 103 out of 668 (15.4%) patients. There was spontaneous normalization in 24 (23.3%), fluctuation in 11 (10.7%) and permanently positive serology in 68 (66%). In 46 out of 53 (86.8%) patients with positive serology and biopsy, CD diagnosis was confirmed by biopsy (BPCD). The frequency of BPCD was 6.9%, and the serology in 76.1% was positive at the time of diagnosis of T1DM. The weight, height and body mass index-standard deviation score at diagnosis were lower in patients with BPCD compared to the group without CD. An anti-tissue transglutaminase-IgA (anti-TTG-IgA) level of 11.8 times the upper limit of normal was the most sensitive (93%) and specific (90%) cut-off for BPCD (area under the curve: 0.95; 95% confidence interval: 0.912-1; p<0.001). Conclusion: In our cohort, the frequency of positive serology for CD was 15.4%, while the rate of BPCD was 6.9%. The majority (97.8%) of cases were diagnosed within the first five years of T1DM. In 23.3% of cases, positive anti-TTG-IgA spontaneously resolved without a gluten-free diet (GFD). Therefore, serological follow-up instead of immediate duodenal biopsy or GFD therapy, particularly for patients with asymptomatic and mild anti-TTG IgA level, is warranted.

A novel diagnostic tool for the evaluation of hypothalamic-pituitary region and diagnosis of growth hormone deficiency: pons ratio.

Backgrounds Limitations in the evaluation of the pituitary size and changes according to pubertal status make its validity questionable. Recently, in a small-scale study, pons ratio (PR) has been suggested as a more sensitive tool for diagnosis and etiological evaluation of growth hormone deficiency (GHD). The aim of the study is to evaluate the diagnostic value of PR in the diagnosis of GHD. Methods We retrospectively evaluated the pituitary magnetic resonance imaging (MRI) of 133 patients with a diagnosis of GHD. Primary axis (PA) was assigned as a line crossing the mid-sagittal dorsum sella and fourth ventricle. PR was defined as the pons height above the PA divided by total pons height. The PR of patients with GHD was compared to subjects without GHD. Results Study included 133 patients with GHD and 47 controls. In total, 121 (91%) patients had isolated GHD and 12 (9%) patients had multiple pituitary hormone deficiency. The PR of the patient group (mean: 0.32 ± 0.89; range: 0.14-0.63) was significantly higher than controls (mean: 0.26 ± 0.067; range 0.19-0.44) (p: 0.000). The optimal cut-off value of PR for GHD diagnosis was 0.27 (sensitivity 71% specificity 56%). There was a negative correlation between anterior pituitary height (APH)-SDS and PR (p: 0.002; r: -0.27). APH was increased, but PR remained unchanged in pubertal patients (p: 0.089). Conclusions PR measurement is a noninvasive, practical method with a cost-benefit clinical value. As it is not affected by pubertal status, PR is potentially a more sensitive tool for evaluation of pituitary gland in GHD patients compared to APH.

Evaluation of the Final Adult Height and Its Determinants in Patients with Growth Hormone Deficiency: A Single-centre Experience from the South-Eastern Region of Turkey

Objective: The aim was to determine the final adult height (FAH) achieved by recombinant human growth hormone (rhGH) treatment, the factors affecting FAH and the success of attaining the genetic potential. Methods: Data of 133 patients treated with rhGH therapy were reviewed retrospectively. Patients were grouped according to diagnosis, either isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD), and by sex, and pubertal status at the beginning of treatment. Results: The mean age of initiation of treatment was 12.3±2.18 years, and the mean duration of rhGH treatment was 3.65±1.5 years. The mean height standard deviation score (SDS) at diagnosis was -3.11±0.75 SD. All patients received a standardized GH dose of 0.033 mg/kg/day. Mean FAH-SDS was -1.8±0.77 and delta height-SDS (the change in height SDS between the beginning and end of treatment) was 1.28±0.94 SD. FAH-SDS was -1.79±0.86 SD in males; -1.82±0.64 in females (p=0.857); -1.94±0.71 at the beginning of treatment in pubertal patients and -1.68±0.81 in prepubertal patients (p=0.056); -1.84±0.89 in patients with IGHD and -0.47±0.2 in patients with MPHD (p˃0.05). In multiple regression analysis, First year delta height-SDS was the most predictive factor for both FAH-SDS and delta height-SDS. Conclusion: The majority of our patients achieved a final height compatible with their genetic potential as well as population standards when treated with rhGH even having started at a relatively late age. First year delta height-SDS was a predictive factor for FAH.