Yeşim Oymak

Observational study comparing long-term safety and efficacy of Deferasirox with Desferrioxamine therapy in chelation-naïve children with transfusional iron overload

Objectives:  An observational study was conducted to explore postmarketing safety and efficacy of Deferasirox (DFX) in comparison with conventional Desferrioxamine (DFO) in chelation‐naïve children with transfusional iron overload.

The effectiveness of tools for monitoring hemophilic arthropathy.

Introduction: Hemophilic arthropathy is the most important cause of morbidity in patients with hemophilia. The earliest alterations that occur during the development of hemophilic arthropathy can be shown using magnetic resonance imaging (MRI). In addition, various tools have been developed to monitor joint health. Aim: The purpose of this study was to determine the correlation between these tools when used to assess hemophilia patients. Methods: This cross-sectional study enrolled 38 hemophilia patients between 2 and 18 years of age. Hemophilia Joint Health Score (HJHS) and radiologic scores (Pettersson and Arnold-Hilgartner) were used to evaluate the joints of the patients (n=236). Magnetic resonance imaging (MRI) was performed on 46 joints that were pathologic according to the HJHS. These joints were imaged bilaterally; therefore, 14 normal joints were imaged. In addition, the Functional Independence Score in Hemophilia (FISH) was used to evaluate the joints of 33 patients. Results: The HJHS scores were correlated with the MRI and FISH scores. The annual bleeding rate was not correlated with any scores; however, the number of painful joints was correlated with the MRI scores. The radiologic scores were correlated weakly with progressive score and HJHS. Conclusion: The agreement between the HJHS scores and the MRI scores suggests that the HJHS may be used safely as a first-line tool. We recommend that the FISH should be used in the routine follow-up of hemophilia patients as a functional evaluation tool. Painful joints may be useful in deciding to apply MRI, whereas the bleeding frequency may not be useful.

A Single Center's Experience with Candida parapsilosis Related Long-Term Central Venous Access Device Infections: The Port Removal Decision and Its Outcomes

Pediatric cancer patients have an increased risk of potentially life-threatening fungal infections such as Candida parapsilosis, associated with long-term CVADs. The Infectious Diseases Society of America (IDSA) guidelines on Candida catheter-related bloodstream infections recommend systemic antifungal therapy and catheter removal. In this study, we focused on our experience with antifungal failure due to totally implanted catheter-associated C. parapsilosis bloodstream infections. We investigated cases leading to port removal in pediatric malignancy patients and the associated patient outcomes. In the first phase of the study, a retrospective chart review was performed to collect patient information, including primary disease; time from hospitalization to port-related candidemia; antifungal drug choice; and the time at which port removal occurred. During the second phase, antifungal susceptibility tests for C. parapsilosis were performed in our microbiology laboratory. All patients had fevers and were neutropenic at the time of candidemia diagnosis. The mean duration between the first isolation of Candida parapsilosis from the port samples to the port removal was 9.75 ± 5.29 days for 11 patients. Patient fevers lasted for a mean time of 16.22 ± 6.51 days. The median recovery duration from fever after CVC removal was four days (range 2–12 days). The median duration for achieving negative blood cultures, following antifungal treatment was 18 days (range 10–27 days). Our data favored the removal of catheters in the presence of ongoing fever, as suggested by the guidelines, independent of the chosen antifungal treatment. Future studies with large samples are needed to evaluate the effects of catheter removal on mortality rates and patient outcomes.

Antibiotic sensitivity and resistance in children with urinary tract infection in Sanliurfa

OBJECTIVE This study aimed to evaluate antibiotic resistance in the province of Şanliurfa and to observe any difference between antibiotic resistance rates. MATERIAL AND METHODS The study comprised 107 children who presented at the pediatric polyclinic with complaints of urinary tract infection with the diagnosis of urinary tract infection and whose urine cultures exhibited bacterial growth. The patients were analyzed with respect to the frequency of proliferating pathogens, sensitivity to the antibiotics used and the rates of developed resistance to the antibiotics. RESULTS A total of 107 patients aged between 1 year and 15 years were included in the study, encompassing 14 (13.1%) males and 93 (86.9%) females. According to the urine culture results, proliferation of Escherichia coli (E. coli) was observed in 69 (64.5%), Klebsiella spp. in 13 (12.1%), Proteus mirabilis in 9 (8.4%), Staphylococcus aureus in 5 (4.7%), Pseudomonas aeruginosa in 5 (4.7%), Acinetobacter spp. in 3 (2.8%) and Enterococcus spp. in 3 (2.8%) patients. For proliferating E. coli, high resistance rates to ceftriaxone (39.5%), nitrofurantoin (19.7%), ampicillin-sulbactam (64.1%), co-trimoxazole (41.5%), amoxicillinclavulanate (51.7%) and cefuroxime (38.1%) were observed. All of isolated microorganisms were resistant to ampicillin-sulbactam, amoxicillin-clavulanate, co-trimoxazole, ceftriaxone, cefuroxime and cefoxitin in decreasing frequencies. The most effective antimicrobial agents were determined to be imipenem, sulpera-zone, quinolone and aminoglycosides. CONCLUSION In our region, parenteral antibiotics that should be selected for the empirical treatment of UTIs in all age groups are the aminoglycosides and 3(rd) generation cephalosporines. In contrast to other studies, these results suggest that co-trimoxazole should be used for children aged 0-1, and 2(nd) generation cephalosporins should be used for the oral treatment of children aged 1-5 due to the low rate of resistance to nitrofurantoin in patients aged over 5 years.

Refugee children with cancer in Turkey

1 Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies—improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol 2015; 26: 1533–46. 2 Abdel-Fatah TMA, Agarwal D, Liu D-X, et al. SPAG5 as a prognostic biomarker and chemotherapy sensitivity predictor in breast cancer: a retrospective, integrated genomic, transcriptomic, and protein analysis. Lancet Oncol 2016; published online June 13. http://dx.doi.org/10.1016/ S1470-2045(16)00174-1. 3 Johansson I, Ringner M, Hedenfalk I. The landscape of candidate driver genes diff ers between male and female breast cancer. PLoS One 2013; 8: e78299. 4 Cornen S, Guille A, Adelaide J, et al. Candidate target genes of luminal B breast cancers identifi ed by genome, gene expression and DNA methylation profi ling. PLoS One 2014; 9: e81843. 5 Finetti P, Guille A, Adelaide J, Birnbaum D, Chaff anet M, Bertucci F. ESPL1 is a candidate oncogene of luminal B breast cancers. Breast Cancer Res Treat 2014; 147: 51–59. 6 Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004; 351: 2817–26. 7 van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002; 347: 1999–2009. 8 Filipits M, Rudas M, Jakesz R, et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res 2011; 17: 6012–20. 9 Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009; 27: 1160–67. 10 Fischer M, Quaas M, Steiner L, Engeland K. The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes. Nucleic Acids Res 2016; 44: 164–74.

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively. None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

Granulocyte transfusion experience in pediatric neutropenic fever: Splitted product can be an alternative?

The granulocyte transfusion (GTX) has been used for a long time due to uncontrolled neutropenic fever with antimicrobial agents. In some cases, the product needs to be splitted for using in the next 12 hours. The aim of this study is to evaluate the efficacy of splitted product and clinical response to GTX. In this study, 15 patients with malignancy with 19 neutropenic fever, who had received 56 GTX, were included. Seventeen of 56 GTX were splitted and used in maximum 12 hours during infections which did not respond to antibacterial and antifungal therapy in 7 days. The patients were divided in to response groups as a complete, partial and progressive. The predictive factors for response group were evaluated. GTX were well tolerated in all patients. The median granulocyte dose was 1.26 (0.38-5.22) × 10(9)/kg. Total response rate was 89.5%. The infection-related mortality rate was 10.5%. Although the granulocyte doses are the same in both of the product groups, an hour later ANC increment of primer product was higher than that of splitted product (p = 0.001). Among the products, 48.7% of primer product and 17.6% of splitted product had induced ≥ 1000/mm(3) ANC increment after an hour (p = 0.039). Granulocyte transfusion is safe and effective in controlling the febrile neutropenia attack. GTX should be applied in a short time to provide effective ANC increment. For now, main granulocyte product instead of splitted product should be preferred in case of uncontrolled neutropenic fever with antibacterial/antifungal agents.

Congenital amegakaryocytic thrombocytopenia: three case reports from patients with different clinical diagnoses and somatic abnormalities.

The congenital amegakaryocytic thrombocytopenia (CAMT) is a syndrome characterized by preservation of granulocytic and erythroid cells during genesis, with a gradual or progressive decrease in the number of megakaryocytic series of cells in the bone marrow. At later times, most patients develop aplastic anemia. It is important to rule out specific causes of thrombocytopenia that develop in the early stages of CAMT. Typically, there are no specific somatic abnormalities that accompany this deadly disease. Here we present three CAMT cases that presented with different clinical diagnoses, with various physical anomalies in two of those cases. The first patient was examined because of a cytomegalovirus infection. The second patient had been referred with a suspected neonatal alloimmune thrombocytopenia, whereas the third patient presented with chronic immune thrombocytopenic purpura. Subsequently, all three patients were diagnosed with CAMT. Two of the patients had physical anomalies. In particular, the first patient had a duplex urinary system. To our knowledge, this is the first patient with CAMT to have a duplicated collecting sysem. The second patient had a secundum atrial septal defect, an atypical facial appearance, and growth retardation. Since CAMT could also be observed outside the neonatal period, the differential diagnosis for thrombocytopenia should be considered for all age groups. Moreover, it should be considered that CAMT may also be accompanied with somatic abnormalities.

A national registry of thalassemia in Turkey; demographic and disease characteristics of patients, achievements and challenges in prevention

Objective: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. Materials and Methods: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with β-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). Results: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all β-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999. Conclusion: While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.

Varicella-Zoster Virus Infections in Pediatric Malignancy Patients: A Seven-Year Analysis

Primary varicella-zoster virus (VZV) infection is a benign self-limited disease. In this study, we review our experience in focusing on the outcome and treatment of VZV infection in pediatric malignancy patients. During the study period, a total of 41 patients with pediatric malignancy had been hospitalized with the diagnosis of VZV infection. All the patients were treated with intravenous acyclovir for a median of 7 days (ranging from 5 to 21 days). The calculated attributable delay of chemotherapy due to VZV infections was 8 days (ranging from 2 to 60 days). VZV-related complications were observed in 3 of 41 patients (7%) who suffered from acute respiratory distress syndrome, and one of them with hemophagocytic lymphohistiocytosis died due to respiratory failure despite acyclovir and broad-spectrum antimicrobial treatment plus supportive treatment. VZV infections are still important contagious diseases in pediatric cancer patients, because they cause not only significant mortality but also a delay in chemotherapy.