Lale Atahan

Reduced incidence of the somnolence syndrome after prophylactic cranial irradiation in children with acute lymphoblastic leukemia

A prospective double blind randomized trial comparing two different dose schedules of continuous steroid coverage during prophylactic cranial radiotherapy (CRT) in leukemic children was conducted to find out the optimum dose to be prescribed to reduce the incidence of Somnolence Syndrome (SS). Between April 1994 and February 1996, 32 patients with acute lymphoblastic leukemia received CRT of 18 Gy in 10 fractions. Patients were randomized to receive oral dexamethasone of 2 or 4 mg/m2 during radiotherapy. The diagnosis of SS was made clinically based on symptoms of somnolence. All patients were followed for a minimum of 8 months. The overall incidence of SS was 40%. The development of SS was steroid dose dependent. In low dose steroid arm the incidence of SS was 64.3% (9/14), compared to 17.6% (3/17) in high dose arm with statistically significant difference (P = 0.008). The median time to development of SS was 4 weeks. The most common symptom of SS was drowsiness followed by anorexia, headache, nausea, vomiting, decreased activity, irritability, fever and ataxia, respectively. The duration of symptoms ranged from 2 to 14 days. The development of SS was not related to the presence of acute reactions, age at the time of CRT and sex. In all cases the symptoms subsided completely and spontaneously. Our results suggest that steroid coverage at a dose of 4 mg/m2 during CRT reduces the incidence of SS. However, a multicentric prospective randomized trial is needed to determine the role and the optimal dose of steroid.

Extrahepatic Hodgkin’s Disease with Intrahepatic Cholestasis: Report of Two Cases

Liver is involved in about 5–8% of newly diagnosed Hodgkin’s disease (HD) cases. The incidence reaches up to 50–60% in postmortem studies. In the literature only a few cases of idiopathic cholestatic jaundice have been described without an apparent cause and a paraneoplastic etiology has been suggested. We report 2 cases with HD presenting with obstructive jaundice without obvious liver involvement. The first case died soon after diagnosis; the second case received chemotherapy and radiotherapy, and she is well at 26 months’ follow-up. Extrahepatic HD with intrahepatic cholestasis is an extremely rare situation without an established approach. Such cases like the present ones may help to understand the pathogenesis of the liver involvement of HD and determine the best management of these cases.

Hodgkin's disease in Turkish children : Clinical characteristics and treatment results of 210 patients

Although Hodgkins disease (HD) is one of the common malignancies in childhood, there is limited information from developing countries in English literature. The aim of this study is to give epidemiologic features and treatment results of 210 previously untreated children with HD from a developing country. Between 1 June 1984 and 31 December 1992, all children seen who were younger than 18 years old with newly diagnosed, untreated, biopsy-proven Hodgkins disease were included in this study. A clinical staging system was used to determine the dissemination of the disease. While patients with stage I-II disease received canapé treatment protocol (three cycles COPP [cyclophosphamide, vincristine, procarbazine, prednisolone] or ABVD [doxorubicin, bleomycine, vinblastine, dacarbazine] plus low-dose involved-field radiotherapy), patients with stage III-IV disease were treated by sandwich protocol (six cycles COPP plus low-dose involved-field radiotherapy). A total of 210 patients with a median age of 8 years were eligible for this study. Male to female ratio was 3:1 and 37 (17.6%) were less than 5 years of age. The major histologic subtype was mixed cellularity (69.6%). Overall survival rates were 91.5 and 87.7%, and event-free survival rates were 71.5 and 70.5% at 5 and 10 years, respectively. No secondary malignancy has been observed so far. The prevalence of Hodgkins disease in young children is higher and the distribution of histologic subtypes is also different from many Western countries. Canapé and sandwich treatment protocols could be used safely in clinically staged childhood HD with tolerable toxicity.

A comparison of the effect of high-dose methylprednisolone with conventional-dose prednisolone in acute lymphoblastic leukemia patients with randomization.

In this preliminary study the efficacy of high-dose methylprednisolone (HDMP) during remission-induction chemotherapy was evaluated on 166 children with acute lymphoblastic leukemia (ALL). The St. Jude Total Therapy Study XI protocol with minor modifications was used in this trial. Patients were randomized into two groups. Group A received conventional-dose (2 mg/kg/day orally) prednisolone, and group B received high-dose methylprednisolone (HDMP, Prednol-L, 900-600 mg/m2 orally) during remission-induction chemotherapy. Complete remission was achieved in 97% of the children. For the 80 patients who were followed up for 3 years, median follow-up was 44 (range 5-60) months and the 3-year event-free survival (EFS) rate was 68.5%) overall, 58.6% in group A and 78.4% in group B. The EFS among patients in group B was significantly higher than in group A (p=0.05). When we compared the 3-year EFS of groups A and B in the high-risk groups and high-risk subgroups with white blood cell (WBC) counts > or = 50 x 10(9)/l and age > or = 10 years, the survival rates were 45% versus 77.2%, 33% versus 78% and 45% versus 89%, respectively. During the follow-up of 162 patients, relapses were significantly higher in group A. Bone marrow relapses in 162 patients, and also in a subgroup of patients > or = 10 years of age were significantly higher in group A. These results suggest that HDMP during remission-induction chemotherapy improves long-term EFS, particularly for high-risk patients.

A comparative study of technetium-99m sestamibi and technetium-99m tetrofosmin single-photon tomography in the detection of nasopharyngeal carcinoma

The intention of this prospective study was to compare the diagnostic potential of technetium-99m sestamibi (MIBI) and a novel radiotracer,99mTc-Tetrofosmin (Tetro), for the assessment of primary nasopharyngeal carcinoma (NPC) and the differentiation of residual disease from post-therapy changes. A total of 38 patients underwent MIBI and Tetro single-photon emission tomography (SPET) imaging at initial presentation (n=22) or following therapy (n=16). The findings were correlated with computed tomography or magnetic resonance imaging (MRI) on a site-by-site basis. Tumour/background (Tm/Bkg) ratios were obtained on coronal sections. Biopsy (nine patients) and/or 12- to 24-month clinical follow-up data were available in the post-therapy group. All primary disease sites were accurately detected by both imaging studies. Although there was no statistical difference between the two imaging techniques in the detection of primary disease, MIBI was superior to Tetro in the detection of regional lymph node metastases (sensitivity: 95% vs 79%). Tetro and MIBI SPET were true-positive in all patients (n=7) with proven residual/recurrent diseuse. In nine patients who had no evidence of residual/recurrent tumour, MRI was false-positive in five while Tetro and MIBI SPET were false-positive in two and three patients, respectively. Tm/Bkg ratios were ≤1.7 in all false-positive cases except one. Tetro, MIBI and MRI had specificities of 78%, 67% and 44%, and accuracies of 87.5%, 81% and 69%, respectively. The results of Tetro and of MIBI SPET were rot statistically different from one another with regard to the prediction of residual/recurrent or metastatic NPC.

Cavoatrial tumor extension in children with wilms tumor: a retrospective review of 17 children in a single center.

The aim of this study was to evaluate the clinical characteristics and treatment results of 17 children with cavoatrial tumor extension of Wilms tumor. Of the 360 Wilms tumors diagnosed between 1980 and 2000, 17 patients with intracaval thrombus were identified from the medical records at the pediatric oncology department of Hacettepe University. The following data were collected and reviewed: age, sex, presenting symptoms, tumor site, presence of anaplasia, stage, associated congenital anomalies, localization of tumor thrombus, radiologic findings, type and duration of preoperative chemotherapy, response to preoperative chemotherapy, recurrences, and survival. The frequency of cavoatrial extension in this group was 4.7% (15 in the inferior vena cava and 2 in the right atrium). Fourteen patients received preoperative chemotherapy consisting of two-drug regimen (vincristine and actinomycin D) ranging from 1 to 12 weeks (median 4 weeks). Since intravascular invasion is often asymptomatic, a careful radiologic examination to detect tumor thrombus before surgery is essential. There is no need for aggressive surgery in the presence of tumor thrombus. It may be resolved by preoperative chemotherapy. Surgical removal of the thrombus should be considered in the presence of life-threatening tumor thrombosis at diagnosis and in patients who had residual thrombus after chemotherapy.

High-dose methylprednisolone for children with acute lymphoblastic leukemia and unfavorable presenting features

Abstract:  In an attempt to improve treatment outcome high‐dose methylprednisolone (HDMP, 20–30 mg/kg, once a day orally) was used instead of a conventional dose of steroid (2 mg/kg/d, in 3 divided doses) in children with acute lymphoblastic leukemia (ALL) with increased risk factors. HDMP combined with cytotoxic agents (vincristine and l‐asparaginase) resulted in an improved complete remission rate (94%) in 48 newly diagnosed children with ALL compared to 81% in 86 historical controls receiving standard dose steroid combined with the same treatment regimen. The bone marrow relapse rate was lower in patients who received HDMP (31%) than in controls (56%). Treatment was discontinued in 56% of 48 patients receiving HDMP and in 35% of 86 controls. The difference was significant (p<0.05). The 5‐yr continuous complete remission rate was significantly greater in patients received HDMP compared with the control patients (60% vs. 43%, p<0.05). HDMP treatment was well tolerated without significant adverse effects. Moreover, during induction therapy the duration of leukopenia (< 2 × 109/L) was shorter in patients receiving HDMP. We conclude that HDMP combined with other antileukemic agents increased the CR rate and prolonged the duration of remission in children with ALL who had increased risk factors. However, the optimal dosage of HDMP and its role in maintenance therapy should be determined in future, randomized studies.

TREATMENT OF WILMS TUMOR: A Report from the Turkish Pediatric Oncology Group (TPOG)

Aim: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey. Methods and patients: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III–IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II–IV UH tumors, VCR + Act-D + ADR + etoposide + RT. Results: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases ≤2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV. Conclusions: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.

The treatment of childhood Hodgkin lymphoma: Improved survival in a developing country

Background. To evaluate the clinical characteristics, treatment regimens, and outcome of children with Hodgkin lymphoma in a developing country over a period of 34 years. Methods. This paper retrospectively evaluates the treatment and prognosis of 614 children with Hodgkin lymphoma disease between 1971 and 2005. All patients were treated with chemotherapy, and also received radiotherapy. Results. There were 452 males and 162 females with a median age of 8 years (2 to 21); 183 patients had B symptoms. There were 165, 185, 145, and 119 patients in stage I, II, III, and IV, respectively. Histopathologic subtypes were mixed cellularity (344 patients), nodular sclerosis (90), lymphocytic predominance (62), lymphocytic depletion (46), unclassified types (69), and nodular lymphocyte predominant Hodgkin lymphoma (3). Overall (OS) and event-free survival (EFS) rates were 83 and 60%, though OS rates varied according to chemotherapy protocol; age; presence of B symptoms, leukocytosis, anemia, and extranodal involvement; and stage at diagnosis. Over the years, the median age of patients increased, as did the frequency of the nodular sclerosing type of disease. Conclusions. This is one of the largest series in a single center. The increase in the median age and in the frequency of the nodular-sclerosing type are thought to be related to the development status of Turkey. The ABVD protocol yielded the best survival rates and should be used for treatment of patients with Hodgkin lymphoma.

Improved survival of children with wilms tumor.

To analyze changes in the overall survival (OS) rate of children with Wilms tumor treated in a single institute over nearly 30 years. This study included 327 children with a newly diagnosed Wilms tumor. Their median age was 3 years, and the male:female ratio was 1.1. Survival rates were analyzed according to the stage of disease, histopathology, and different treatment regimens used between 1972 and 1999. At diagnosis, 51.1% of patients had advanced stage disease. Ten patients had anaplasia, and; 97% (317 patients) of the tumors had favorable histopathology. The 10-year OS rate was 60.6% for the entire group, but varied according to the years in which the patients were treated, the chemotherapy regimen, and stage of disease. Patients treated during the periods of 1972 to 1979, 1980 to 1989, and 1990 to 1999 had 10-year OS rates of 48.5%, 64.3%, and 72.8%, respectively. The 10-year OS rate in children treated with actinomycin only was 36.7% compared with 48% for children treated with the actinomycin-D+vincristine regimen with a 3-month interval, 67% for the actinomycin-D+vincristine regimen with a 1.5-month interval, 54.5% for the poor-risk regimen (actinomycin-D, vincristine, cyclophosphamide, and adriamycin), and 53.4% for the SIOP-9 protocol. Children with stage I to IV disease had 10-year OS rates of 75%, 77.1%, 54.4%, and 30.4%, respectively. The 10-year OS rates for children with stage III and IV disease increased from 46.4% and 13.4% for patients treated between 1972 to 1979 period to 75% and 54.5% for children treated during 1990 to 1999. The 10-year OS rate for children with Wilms tumor improved as treatment strategies evolved, illustrating that pediatric oncology in Turkey is developing parallel to the Western world.