Hanafy Hafez

Comparison of toxicity following different conditioning regimens (busulfan/melphalan and carboplatin/etoposide/melphalan) for advanced stage neuroblastoma: Experience of two transplant centers.

The outcome for advanced neuroblastoma has improved with combined modality therapy: induction chemotherapy, surgery, and consolidation with high‐dose chemotherapy/autologous HSCT, followed by local radiation, cisretinoic acid, and recently antibody therapy. In the United States, the most common conditioning regimen is CEM, while in Europe/Middle East, Bu/Mel has been widely used; it remains unclear which regimen has the best outcome. Assess renal, hepatic, and infectious toxicity through Day+100 in 2 different regimens. Retrospective comparison between CEM‐DFCHCC Boston and Bu/Mel‐ CCHE‐57357. Thirty‐five patients, median age 4, in Boston (2007–2011) and 38 patients, median age 3, in Cairo (2009–2011). Renal toxicity; creatinine was significantly higher in CEM than Bu/Mel: 57% (median day+90) vs. 29% (median>day+100), p = 0.004. One CEM patient died from renal dialysis at day+19. Hepatic toxicity was significantly higher in CEM than Bu/Mel: 80% (median day+26) vs. 58% (median day+60), p = 0.04. In infectious complications with CEM 14%, bacteremia (n = 4) and fungemia (n = 1), 3 had culture‐negative sepsis requiring vasopressors. With Bu/Mel 18%, bacteremia (n = 7), none required pressors, p = 0.4. Bu/Mel was associated with less acute hepatic and renal toxicity and thus may be preferable for preserving organ functions.

Prophylactic levofloxacin in pediatric neutropenic patients during autologous hematopoietic stem cell transplantation.

Using fluoroquinolone prophylaxis in pediatric neutropenic patients is a controversial issue due to the concern about emergence of resistant strains in addition to the lack of pediatric studies. This study was performed to assess the effectiveness of levofloxacin prophylaxis in pediatric patients during autologous stem cell transplantation.

Profiling Loss of Heterozygosity Patterns in a Cohort of Favorable Histology Nephroblastoma Egyptian Patients: What is Consistent With the Rest of the World.

According to the Fifth National Wilms Tumor Study (NWTS-5), tumor-specific loss of heterozygosity (LOH) for chromosomes 1p and 16q identifies a subset of patients with Wilms tumor (WT) who despite having favorable histology (FH) have a significantly increased risk of relapse and death. We aimed to find out 1p and 16q LOH frequencies in patients with FH-WT as well as its correlation to survival outcome and epidemiologic and clinical characteristics. Data of patients with FH-WT presenting to the National Cancer Institute, Egypt, were retrospectively analyzed. Paraffin blocks were tested for 1p and 16q LOH using polymorphic loci that span the minimal regions of LOH at this area. The study included 100 patients with a median age of 5 years. Thirty-nine patients (39%) showed LOH at 1p (n = 14), 16q (n = 13), or both (n = 12). LOH was most frequently encountered in patients above 10 years (5/5), advanced stages disease (80% of stage V and 50% of stages IV and III each). The 3-year overall survival (OS) and event-free survival (EFS) were significantly lower in patients with double LOH (75% and 50%, respectively), followed by 16q (92% and 54%), in comparison with 1p (93% each) and negative LOH (97% and 100%) cases, respectively (p = 0.001). Combined LOH (1p+16q), followed by 16q LOH alone, was predictive of poorer outcome and was associated with lower OS and EFS in patients with FH-WT. Our results showed a higher-risk disease that would suggest the need for an intensified upfront therapy in this group of patients.

Hepatoblastoma in Developing Countries; Eight Years of Single Centre Experience

Background and objectives: Although hepatoblastoma (HB) is a rare childhood tumor and constitutes only 0.9% of all pediatric cancers, there was an obvious improvement in risk stratification and prognosis over the last two decades. This study aimed to assess the outcome of HB patients treated in our center and to investigate the impact of different prognostic factors on the survival of these patients. Patients and methods: This was a retrospective study included newly diagnosed patients with HB presented to the Children Cancer Hospital Egypt (CCHE 57357), from July 2007 to June 2015. Patient’s data were analyzed for the clinical characteristics and survival outcome of the included patients. Results: One hundred twenty-four children were included during the study period with a median age of 14 months. The tumor was found occupying the entire liver in 25 patients (20%); while it was confined to one lobe in 80% of them, portal vein thrombosis was diagnosed in 10 patients, and there were 30 patients (24%) had metastatic disease at presentation. Only five patients (4%) underwent primary surgical excision, and all of them were grossly excised (stage I); 77/119 (64.7%) experienced delayed surgery after two to six courses (median, four courses) of C5VD and the overall resection rate was 66%. There were 42 patients (35.3%) failed to do surgical excision either because they still had evident metastatic disease with poor chemotherapy response, or because their tumor remained unresectable after six courses of chemotherapy. The 3-year event-free and overall survivals for the whole studied patients were 45.7% (95% CI, 36.9% - 56.7%), and 66.7% (95% CI, 57.1% - 77.8%) respectively. The 3-year EFS and OS were significantly better in those who underwent surgical excision (68.63% and 80.74% respectively, P-value 0.001). Also, the survival rates were significantly affected by the presence of metastatic disease at presentation, tumor stage and initial risk grouping of the studied patients. Conclusion: Surgical excision, tumor stage and COG risk grouping are the main prognostic variables affecting patients’ outcome. Efforts to achieve resectability of the tumor either by advanced surgical techniques or by developing effective preoperative treatment, especially for advanced and metastatic disease, are mandatory.

Surgical approaches, anaesthetic management and outcome in pediatric superior mediastinal tumors

BACKGROUND Pediatric superior mediastinal tumors are a heterogeneous group of tumors with marked variation in pathology and extension. We reviewed our experience with different surgical approaches to tumors originating from or extending to superior mediastinum in pediatrics. PATIENTS AND METHODS The medical records of all patients who had undergone resection for superior mediastinal tumors in Childrens Cancer Hospital - Egypt, between January 2008 to December 2015, were reviewed for demographic data, clinico-pathological features, radiologic findings, operative techniques and outcome. RESULTS The study included 20 patients. Diagnosis included: germ cell tumors (n=8), neuroblastoma (n=4), soft tissue sarcoma (n=3), thymolipoma (n=2), infantile fibromatosis (n=1), calcifying fibrous tumor (n=1), and thymic carcinoma (n=1). Tumor extension was divided into tumors extending unilaterally to one hemithorax (n=9), tumors extending bilaterally to both hemithoraces (n=4), and cervico thoracic junction tumors (n=7). Extended lateral thoracotomy was used in 8 patients. Other approaches included trapdoor (n=5), clamshell (n=4), cervical approach (n=2) and double level lateral thoracotomy (n=1). There was no perioperative mortality, and postoperative morbidity was 20%. At the end of December 2016, 15 patients were alive free of disease, 5 patients developed local and/ or distant relapse. CONCLUSION Pediatric superior mediastinal tumors could be divided into 3 groups according to tumor extension. Each group has an optimum surgical approach that achieves the best exposure for adequate resection. However, further research is needed to confirm the conclusion as this was a descriptive study and the sample size was too small for valid statistical analysis.

Impact of CYP1A1, GSTP1 and XRCC1 genes polymorphisms on toxicity and response to chemotherapy in childhood acute lymphoblastic leukemia

BACKGROUND Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The interindividual genetic variations in drug metabolizing enzymes and DNA repair genes influence the efficacy and toxicity of numerous chemotherapeutic drugs affecting the treatment outcome. AIM OF THE WORK The aim of the study was to investigate the impact of drug metabolizing CYP1, GSTP1 and DNA repair (XRCC1) genes polymorphisms on the toxicity and response to chemotherapy in childhood ALL. PATIENTS AND METHODOLOGY Ninety seven ALL pediatric patients were genotyped for CYP1A1, GSTP1 ILe105Val and XRCC1 Arg194Tryp single nucleotide polymorphisms (SNPs) using PCR-RFLP. RESULTS No statistically significant differences were observed between the wild and variant (homozygous and heterozygous) genotypes of the polymorphisms studied in CYP1A1, GSTP1 or XRCC1 genes regarding age, total leukocyte count, immunophenotyping, cytogenetic or risk group. The SNPs in CYP1A1, GSTP1 and XRCC1 genes did not show significant association with complete remission (CR) rate, overall survival (OS) or event free survival (EFS). However, XRCC1 Arg194Trp SNP was associated with higher drug toxicity; carriers of variant genotypes (CT and TT) had a significantly higher frequency of myelosuppression compared to those with the wild CC genotype (21/43[48.8%]) compared to (14/54[25.9%]) (p=0.020). The analysis of the combined effect of studied SNPs did not show any significant association with patient outcome. CONCLUSION Our study reported a significant association between the DNA repair gene polymorphism and myelosuppression in childhood ALL patients. Adjustment of the dose of chemotherapeutic agents according to XRCC1 Arg194Trp polymorphism may improve outcome in cases with risk of toxicity.