Inci Ilhan

Frequency of mtDNA A1555G and A7445G mutations among children with prelingual deafness in Turkey

Considerable differences on the frequencies of the mitochondrial 12S rRNA A1555G and tRNASer(UCN) A7445G mutations have been reported in different populations. Our screening of 168 patients coming from independent Turkish families with prelingual sensorineural non-syndromic deafness revealed three deaf children with A1555G (1.8%) but no examples of A7445G. One proband with the mitochondrial A1555G mutation has also evidence for right parietal infarct on a brain imaging study, for which common thrombotic mutations were found to be negative. Conclusion: This study shows that the mitochondrial A1555G mutation is among the significant causes of prelingual non-syndromic deafness in the Turkish population.

Subcutaneous sacrococcygeal myxopapillary ependymoma

We report an 8-year-old boy with a primary subcutaneous sacrococcygeal ependymoma, a rare tumor that is thought to arise in embryologic rests. The lesion was completely removed in our patient, who has been followed without recurrence for 20 months. Our experience, together with that of the other 15 cases in the world literature, supports surgical excision as the mainstay of treatment.

High-dose ifosfamide in relapsed pediatric osteosarcoma: Therapeutic effects and renal toxicity

Sixteen pediatric osteosarcoma patients, previously treated with conventional chemotherapy (including ifosfamide (IFX), 9 g/m2) were retreated with high‐dose ifosfamide (HD‐IFX, 14 g/m2 per course), following relapse or development of a new bone tumor. The objective was to obtain responses and an improved event‐free survival (EFS).

NASOPHARYNGEAL CARCINOMA IN TURKISH CHILDREN: Review of 33 Cases

A retrospective and prospective analysis is reported of epidemiological, clinical, and therapeutic aspects of 33 children with nasopharyngeal carcinoma who were treated in a single institution over a period of 10 years. Twenty-three male and 10 female children ranging from 9 to 17 years were referred to our center. Histopathology was WHO type 3 carcinoma in 21, WHO type 2 in 8, WHO type 1 in 1, and unclassified in 3 patients. Disease extent was T2a (n = 15), T2b (n = 2), T3 (n = 11), and T4 (n = 5); N1 (n = 5), N2 (n = 12), and N3a (n = 16). Five patients had base of skull invasion. Four patients had M1 disease on admission. Four patients were treated with irradiation only. Three patients received neoadjuvant, 4 patients received adjuvant, and 22 patients received neoadjuvant + adjuvant chemotherapy in addition to radiotherapy. Patients received 50-72 Gy to the primary tumor and involved nodes and 45-50 Gy to uninvolved regions. Chemotherapy consisted of combinations of cisplatin, fluorouracil or Adriamycin, vincristine, and cyclophosphamide. Twenty-nine patients (88%) attained locoregional control. Overall, 10 patients died with progressive disease or infectious complications, and 2 patients are still receiving therapy. Three patients are still living with multiple metastases and stable disease. Eight patients were lost to follow-up. Twelve patients are alive without relapse 3 and 63 months from diagnosis. Seven patients had 6 relapses at distant and 1 relapse at local site. The median time for first relapse was 8 months. Overall, the 5-year survival rate was 63% and disease-free survival rate was 53%. Although the locoregional control rate is high, long-term survival rates will be the real test of the impact of chemotherapy. Further studies are needed to confirm the optimal combination of effective chemotherapeutic agents and radiotherapy.

Hepatitis B vaccination in children with cancer.

Between September 1991 and April 1993 the hepatitis B vaccination with recombinant hepatitis B vaccine was administered in 41 cancer patients following first diagnosis. All patients were under 16 year of age, with negative hepatitis B virus (HBV) serology and normal hepatic function. They received 40 micrograms of vaccine by injection into the deltoid muscle at 0, 1, and 2, months, with a fourth dose planned at the 4th month for nonresponders. At 1 year a booster dose was given. All the patients began vaccination within 1 month following diagnosis, and periodic serologic follow-up was performed immediately after each vaccination and also in the 6th, 9th, and 12th months after vaccination. Patients with production of anti-HBs at a titer equal to or greater than 10 mIU/L were considered seropositive. The seroconversion rates were 12.4%, 21.9%, 41.0%, and 48.7% after the first, second, third, and fourth monthly doses, respectively. Seroconversion rates were 56.0% at 6 months, 67.5% at 9 months, and 70.5% at 12 months. Geometric mean antibody titers were 212 and 373 mI U/L at 9 and 12 months, respectively. No serious side effects were observed. HBV vaccination is recommended for pediatric cancer patients.

Screening the SLC26A4 gene in probands with deafness and goiter (Pendred syndrome) ascertained from a large group of students of the schools for the deaf in Turkey

To the Editor: Pendred syndrome (PS) (OMIM no. 274600), initially described as deafness and goiter, has been reported as the most common form of syndromic hearing loss, with a prevalence of 4–10% among deaf probands (1). Mutations in the SLC26A4 gene, encoding for a chloride-iodide transporter protein, pendrin, are responsible for the syndrome (2, 3), as well as non-syndromic deafness associated with enlarged vestibular aqueduct (EVA) or Mondini dysplasia (4–6). Although two previous reports included two Turkish families with PS (7, 8), a systematic search for the frequency of this syndrome or mutation analysis in the Turkish population has not been reported before. The study was approved by the Ethics Committee at the Ankara University School of Medicine in 2001. We have visited residential schools in cities of Ankara, Amasya, Afyon, Denizli and Isparta; evaluated students for the presence of environmental causes of their hearing loss or syndromic forms of deafness using a standard questionnaire and physical examination form. Pedigrees of all students were also drawn and blood samples were obtained after informed consent forms were signed by parents. A total of 333 probands with pre-lingual-onset severe to profound sensorineural hearing loss (193 males and 140 females; ages ranging from 7 to 25 years), coming from reportedly independent 293 families, were included in the study after exclusion of students where unequivocal evidence was present for an environmental etiology. A palpable goiter was noted in 11 probands (3.3%) coming from eight independent families (3%). None of these students had been diagnosed with PS before. DNA was extracted from peripheral blood using the phenol-chloroform method. Co-segregation of the phenotype with microsatellite markers (D7S496, D7S2459, D7S3074, D7S2456) flanking the SLC26A4 gene within a 0.8-cM region was evaluated with denaturing polyacrylamide gel electrophoresis followed by silver staining. Mutation screening was performed for 21 exons and intron/exon boundaries using SSCP at 4 C followed by silver staining. Previously described primer pairs were used for PCR amplifications (9, 10). Samples with band changes were directly sequenced after cycle sequencing reactions using an automated sequencer (Beckman Coulter CEQ 2000). All samples were also screened and found to be negative for mutations in the GJB2 gene and for the A1555G mutation in the mtDNA with previously described protocols (11, 12). Characteristics of probands included in the screening are summarized in Table 1. In one family (A137), four sibs and a cousin had deafness and goiter (Fig. 1). All four affected siblings in this kindred had short stature, dry skin and hair, and coarse facies, which suggested early onset hypothyroidism. Two older brothers (A137-101 and 102) in this family were students of the school for the deaf and were on thyroid hormone replacement therapy because of hypothyroidism. Two younger siblings (A137103 and 104), however, were diagnosed as having hypothyroidism only after our screening. In the same small village where this family lives, two other families with non-syndromic hearing loss were identified. Questioning for the goiter or the clinical findings of hypothyroidism in other people of this village was negative. Microsatellite analyzes were suggestive of cosegregation of SLC26A4 with the phenotype in family A137 (Fig. 1). Although homozygosity for most of the markers was evident in other probands with parental consanguinity, there Clin Genet 2003: 64: 371–374 Copyright # Blackwell Munksgaard 2003 Printed inDenmark. All rights reserved CLINICALGENETICS ISSN 0009-9163

Irinotecan and Temozolamide Treatment for Relapsed Ewing Sarcoma: A Single-Center Experience and Review of the Literature

Long-term survival in relapsed Ewing sarcoma (ES) is less than 20%. Encouraging results have been reported with irinotecan and temozolomide combinations (IRN/TMZ). We aimed to share our experience and compare it with previously published studies using this combination to treat relapsed ES. We retrospectively evaluated 20 patients treated with a combination of IRN (20 mg/m2/d × 5 for 2 weeks) and temozolomide (100 mg/m2/d × 5). Patients received a total of 97 courses. An objective response was achieved in 11 patients (55%) and maintained for a median of 12 months. Five patients were alive for a median of 12 months. Median time to progression was 5.5 (2–57) months. After the IRN/TMZ treatment, 1-year overall and event-free survival rates were 54.2% and 44.4%, respectively. Grade 3–4 toxicities included diarrhea (9.2%), neutropenia (11.3%), and thrombocytopenia (6.2%). Three retrospective trials were found in our literature review, which used an IRN/TMZ combination to treat ES. There was one other study which retrospectively evaluated the efficacy of vincristine, IRN, and TMZ combination in relapsed ES. A total of 81 patients were treated with IRN/TMZ in four studies including ours. The objective response rate was 55.1%, and median time to progression ranged from 5.5 to 8.3 months. Twenty-six (7.5%) of a total of 346 courses were associated with grade 3–4 diarrhea. Grade 3–4 neutropenia and thrombocytopenia were reported in 9.2% and 7.2% of the courses, respectively. Results showed that an IRN/TMZ combination is effective and tolerable in patients with relapsed ES.

Treatment results of the Ewing sarcoma of bone and prognostic factors

The purpose of this study is to assess the clinical outcome of patients with ESFT of the bone treated with the European Intergroup Cooperative Ewings Sarcoma Study (EICESS)‐92 treatment protocol at a single center, and to identify prognostic factors.

Quantitative thallium-201 scintigraphy in childhood osteosarcoma: Comparison with technetuim-99m MDP and magnetic resonance imaging in the evaluation of chemotherapeutic response.

The aim of this study was to assess early (15 min) and late (2 h) thallium-201 (201Tl) uptake in children with osteosarcoma and to compare these findings with magnetic resonance imaging (MRI) and technetium-99mAu: Technetuim or Technet.Au: Scan page missing. Disk Fellow. Pls. Check. methylenediphosphonate (99mTc MDP), with emphasis on evaluating tumor viability before and after chemotherapy. Fifteen patients with biopsy-proven osteosarcoma received standard preoperative chemotherapy with a combination of cisplatin, Adriamycin, and high-dose methotrexate. Their ages ranged between 7 and 18 years (median 14.5 years). All patients had 201Tl, 99mTc MDP, and MRI studies. Thallium scintigraphy was performed at 15 min and 2 h after IV injection of 92 MBq of thallium. Thallium uptake ratio was calculated by dividing the count density of the lesion (L) by that of the controlateral normal (N) area. The percent reduction of 201Tl uptake ratio (alteration ratio) was calculated by [100 × (prechemotherapy L/N − postchemotherapy L/N)/prechemotherapy L/N]. Pathologic changes were graded on the basis of % tumor necrosis as defined histologically. Scintigraphic comparisons demonstrated a high-degree of correlation with late 201Tl alteration ratio and poor correlation with both early 201Tl and 99mTc MDP alteration ratios. Late 201Tl images were superior to early 201Tl, 99mTc MDP, and MRI in predicting tumor response to chemotherapy as determined by% tumor necrosis (p <. 01). The authors found that late 201Tl was an accurate test for evaluating the response to specific therapeutic regimens and it can be useful planning surgery or choosing alternative chemotherapeutic regimens.

Comparison of Filgrastim and Lenograstim in Pediatric Solid Tumors

Purpose: Chemotherapy-induced febrile neutropenia (FEN), which causes treatment delays or chemotherapy dose reductions, is a serious side effect of cancer treatment. In Turkey, recombinant G-CSF (rG-CSF) has been used since 2000 to control neutropenia. The purpose of this prospective randomized study is to compare the effectiveness, toxicities and the cost of these two drugs in children. Methods: Between April and December 2008, 29 patients were administered 40 courses of chemotherapy in each arm. A randomized crossover study was designed. All patients were administered rG-CSF 24 hours after the last day of chemotherapy as a secondary prophylaxis. Complete blood counts as well as peripheral blood progenitor (CD34+) cell levels were measured before G-CSF treatment and on the fifth and the seventh day of treatment. Results: The median duration of neutropenia, FEN, the length of hospitalization, the incidence of FEN, and documented infection was not different between the two rG-CSF treatment groups. Erythrocyte and platelet transfusion rates were also similar. After 7 days, the mean leukocyte (WBC [white blood cell]) and neutrophil count (ANC [absolute neutrophil count]), hemoglobin and platelet levels were not significantly different. However, the CD34+ cell level was significantly higher in the lenograstim group. Lenograstim was also more expensive than filgrastim. No serious side effects were reported for either rG-CSF treatment. Conclusions: There is no difference following the administration of either lenograstim or filgrastim for the duration of neutropenia, FEN or hospitalization for pediatric cancer patients. For stem cell mobilization, lenograstim was superior to filgrastim.