Prognostic Factors and Treatment Outcome of Relapsing and Refractory Pediatric Mature B-cell Non-Hodgkin Lymphoma, Children's Cancer Hospital Egypt Experience.

BACKGROUND: Relapsed non-Hodgkin lymphoma treated by chemotherapy and hematopoietic stem cell transplantation (HSCT) has a dismal prognosis. PATIENTS: It is a retrospective study, including pediatric patients diagnosed as mature B-cell non-Hodgkin lymphoma who were primarily refractory or relapsed over 8 years at CCHE. The aim of the study was to analyze the prognostic factors and outcomes of this group of patients. Our result is, 53 of 750 (7%) patients were included. Thirty-four (64.2%) patients had Burkitt lymphoma. Forty-eight (90.6%) patients received LMB 96 protocol initially. The median delay of duration between chemotherapy cycles in first-line treatment was 37 days. Thirty-five (66%) patients relapsed, 23 (65.7%) of them relapsed early, whereas 18 (34%) had tumor progression. Thirty-one (58.5%) patients presented with stage IV at the time of relapse. rituximab, ifosfamide, carboplatin, etoposide was the second line of treatment in 42 (79.24%) patients, and complete second remission was achieved only in 13 (24.3%) patients. Allogeneic HSCT was done for 4 (7.5%) patients, and auto HSCT was done for 3 (5.7%) patients. Three years of overall survival for relapsed and progressed patients were 35.3% and 11.1%, respectively, with a P-value of 0.009. Three years overall survival for patients who underwent HSCT was 85.7% compared with 18.1% for no HSCT with a P-value of 0.007. CONCLUSIONS: The relapse rate is higher than literatures because of the delay of duration between chemotherapy cycles in first-line treatment and more advanced stage at time of relapse. Progression of the disease had a worse outcome than relapse. HSCT in patients with the second remission markedly improved the outcome.

Novel strategies of essential oils, chitosan, and nano- chitosan for inhibition of multi-drug resistant: E. coli O157:H7 and Listeria monocytogenes.

Despite the wide range of available antibiotics, food borne bacteria demonstrate a huge spectrum of resistance. The current study aims to use natural components such as essential oils (EOs), chitosan, and nano-chitosan that have very influential antibacterial properties with novel technologies like chitosan solution/film loaded with EOs against multi-drug resistant bacteria. Two strains of Escherichia coli O157:H7 and three strains of Listeria monocytogenes were used to estimate antibiotics resistance. Ten EOs and their mixture, chitosan, nano-chitosan, chitosan plus EO solutions, and biodegradable chitosan film enriched with EOs were tested as antibacterial agents against pathogenic bacterial strains. Results showed that E. coli O157:H7 51,659 and L. monocytogenes 19,116 relatively exhibited considerable resistance to more than one single antibiotic. Turmeric, cumin, pepper black, and marjoram did not show any inhibition zone against L. monocytogenes; Whereas, clove, thyme, cinnamon, and garlic EOs exhibited high antibacterial activity against L. monocytogenes with minimum inhibitory concentration (MIC) of 250-400 µl 100-1 ml and against E. coli O157:H7 with an MIC of 350-500 µl 100-1 ml, respectively. Among combinations, clove, and thyme EOs showed the highest antibacterial activity against E. coli O157:H7 with MIC of 170 µl 100-1 ml, and the combination of cinnamon and clove EOs showed the strongest antibacterial activity against L. monocytogenes with an MIC of 120 µl 100-1 ml. Both chitosan and nano-chitosan showed a promising potential as an antibacterial agent against pathogenic bacteria as their MICs were relatively lower against L. monocytogenes than for E. coli O157:H7. Chitosan combined with each of cinnamon, clove, and thyme oil have a more effective antibacterial activity against L. monocytogenes and E. coli O157:H7 than the mixture of oils alone. Furthermore, the use of either chitosan solution or biodegradable chitosan film loaded with a combination of clove and thyme EOs had the strongest antibacterial activity against L. monocytogenes and E. coli O157:H7. However, chitosan film without EOs did not exhibit an inhibition zone against the tested bacterial strains.

Productivity of 18F-FDG-PET/CT Diagnostic Tool in the Management of Pediatric Lymphoblastic Lymphoma.

BACKGROUND: Lymphoblastic lymphoma (LL) comprises approximately 20% of childhood non-Hodgkin lymphoma (NHL); however, few studies had investigated the role of 18F-FDG-PET/CT in pediatric LL patients. We aim in this study to assess the role of 18F-FDG-PET/CT in the initial staging of newly diagnosed pediatric patients with LL as well as in the assessment of response after induction chemotherapy. PATIENTS AND METHODS: A prospective study enrolled biopsy proven newly diagnosed pediatric LL patients presenting in the Children Cancer Hospital Egypt (CCHE) during the period from October 2014 to October 2016. 18F-FDG-PET/CT was done initially before therapy and after induction chemotherapy in all patients. The patients were followed until the end of April 2018 (mean 23.5 months). RESULTS: All lymphoma involvement lesions (n = 43) were FDG avid and the intensity of nodal FDG uptake was variable. Two patients (11%) had bone marrow (BM) involvement by < 25% blast cells with corresponding positive BM focal uptake in 18F-FDG-PET/CT (SUVmax = 4 and 4.5). Evaluation post induction phase; CT detected 8 residual lesions in 8 patients (44.4%), while 18F-FDG-PET/CT detected only 3 Deauville-positive residual lesions in 3 patients (16.6%). No intensification of therapy was done in all post-induction positive patients. Repeated 18F-FDG-PET/CT at week 18 for post-induction patients revealed cleared all Deauville-positive residual lesions. On the other hand, repeated CT at week 18 detected regression but still residual in 4/8 (50%) post-induction CT lesions with clearance of the rest (50%). CONCLUSION: In initial staging, 18F-FDG-PET/CT is a useful tool for disease extent evaluation of pediatric LL. Moreover, it could provide a diagnostic hint for BM involvement. 18F-FDG-PET/CT done after induction therapy has a good negative predictive value with higher specificity than CT alone, but is not an indication for treatment intensification due to false positive results. However, larger sample size is required for better conclusion.

Prognostic Factors and Treatment Outcome of Pediatric Anaplastic Large Cell Lymphoma Treated at the Children Cancer Hospital Egypt.

INTRODUCTION: The aim of the current study is to report the epidemiologic data, response rate, treatment outcome, and overall survival of anaplastic large cell lymphoma (ALCL) patients during the 8-year period. PATIENTS AND METHODS: A retrospective study included all patients with newly diagnosed ALCL from July 2007 till December 2015. RESULTS: A total of 48 patients were enrolled. The majority (66.7%) were male individuals. Twenty-one patients (43.7%) were low stage I or II, whereas 27 (56.2%) had advanced stage III or IV. Two patients (4.2%) died during induction chemotherapy. Disease status at last follow-up showed 35 patients (72.9%) in complete remission, 5 (10.5%) relapse, and 5 disease progression. The median time to relapse was 17.2 months. Four patients (8.4%) were salvaged by high-dose chemotherapy ifosphamide, carboplatine, etoposide followed by autologous hematopoietic stem cell transplantation, whereas 5 (10.5%) died out of disease progression. The 5-year overall survival and event-free survival were 81.2% and 68.6%, respectively. Median FU period was 58.7 month. Multivariate analysis included age, sex, stage, and response to chemotherapy and showed no statistical significance. CONCLUSION: Treatment of ALCL according to the Children's Oncology Group ANHL 0131 protocol is well tolerated. The relapsing patient could be salvaged by high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

Role of FDG-PET scan in the management of pediatric mature B cell non-Hodgkin's lymphoma. CCHE experience.

AIM OF WORK: To evaluate the sensitivity (Se), specificity (Sp), and predictive values (PV) of PET scan during management of pediatric mature B cell non-Hodgkin's lymphoma (NHL) in comparison with conventional computed tomography (CT) scan. PATIENTS AND METHODS: A retrospective study enrolled on pediatric NHL patients at Children Cancer Hospital Egypt (CCHE) during the period from July 2007 to the end of June 2013. RESULTS: For 115 pediatric patients diagnosed with mature B cell NHL, 152 PET and 152 CT scans were done simultaneously. Median age was 5.7years. They were 85 males (74%) and 30 females (26%). One hundred twenty six scans (82.9%) were done for 100 (87%) Burkitt lymphoma (BL) patients, while 26 scans (17.1%) were done for 15 (13.0%) patients with diffuse large B cell NHL (DLBC). Nineteen examination (12.5%) were done before starting chemotherapy (group 1), 107 (70.3%) at time of evaluation (group 2), and 26 (17.1%) during follow up (group C). Overall sensitivity was 91.6% for PET and 70.0% for conventional CT (p=0.02). Specificity was 84.1% for PET and 58.9% for CT (p<0.001). Positive predictive value (PPV) for PET was 50%, while was 22% for CT scan (p<0.001). Negative predictive value (NPV) for PET was 98%, and 92% for CT (p=0.01). CONCLUSION: PET scan is significantly more sensitive than conventional CT in the management of aggressive pediatric mature B cell NHL. PET negativity is an excellent indicator of tumor response.

Did salvage ICE chemotherapy improve the outcome in primary resistant/relapsing stage III/IV neuroblastoma?

BACKGROUND AND PURPOSE: Neuroblastoma is the most common extracranial and deadly solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at "high risk" of treatment failure. The aim of this study is to evaluate the response rate of salvage chemotherapy by the ICE (Ifosfamide, Carboplatin, and Etoposide) regimen when administered to previously treated primary refractory or progressive high risk neuroblastoma patients. PATIENTS AND METHODS: Sixty-six patients from the National Cancer Institute (NCI), Cairo University and the Children Cancer Hospital Egypt (CCHE) received salvage chemotherapy (ICE) either due to primary resistance in 51/66 (77.2%) or due to disease progression on primary chemotherapy in 15/66 (22.8%). RESULTS: They were 40 males (60.6%) and 26 females (39.4%). Patients' age ranged between 3 months and 12.5 years. The most common tumor site was suprarenal, followed by retroperitoneal mass. Two patients (3%) died from chemotherapy toxicity during ICE administration. Evaluation of tumor response in the remaining 64 patients showed the following: CR/PR in 24 patients (36.5%), SD in 11 patients (16.6%), and PD in 29 patients (43.9%). Fourteen patients (21.2%) were considered eligible for auto BMT, while 50/64 patients (78.8%) failed this second line (salvage) chemotherapy and had palliative lines of therapy. By the end of the study (May 2010), 47/66 (71.2%) of the patients were still alive, while 19/66 (28.8%) were dead. Two out of 14 patients (14.2%) who underwent HSCT died from post transplantation disease progression, while 12/14 (85.8%) were in CCR. CONCLUSION: Chemotherapy by ICE for primary resistant or progressive stage III/IV NB seems well tolerated. With a 36.6% response rate, 18% CCR, and 3% treatment mortality rate, it could be considered a good salvage therapy in the category of patients who are condemned for palliation.

Management Head and Neck Ewing's Sarcoma Family of Tumors: Experience of the National Cancer Institute, Cairo University.

BACKGROUND: Ewing's sarcoma accounts for 4-6% of primary malignant bone tumors and it affects the head and neck in only 1-4% of cases. The purpose of this study was to review the NCI experience with Ewing's sarcoma of the head and neck in children. PATIENTS AND METHODS: A retrospective analysis of patient files with head and neck Ewing's sarcoma treated at the National Cancer Institute, Cairo University, Egypt, during the period from 1997 to 2008 was done. Files were reviewed and data for patients, tumor and treatment profile were extracted. RESULTS: Twenty patients out of 280 with Ewing's sarcoma were identified during an 11-year period. Patients had a median age of 11.5 years (range 5 months - 22 years) with a male to female ratio of 1:1. The most common tumor site was in the mandible (9/20, 45%) followed by a neck mass (4/20, 20%) and a clavicular mass (3/20, 15%). Six patients (30%) were metastatic at presentation. Most of the patients (19/20, 95%) received chemotherapy. Local therapy was in the form of radical radiotherapy for 8 patients (40%), 2 patients (10%) had surgery alone, while five patients (25%) had surgical resection and postoperative radiotherapy. Overall survival ranged from 1 to 128 months, with a median of 36 months. At the end of the study, 9 patients (45%) were alive in CR, 6 (30%) were lost to FU in disease progression, while 5 patients died from disease progression. CONCLUSION: Ewing's sarcoma of the head and neck is a disease of a rare incidence with debate about the optimum local therapy. Small non-metastatic tumors with good response to chemotherapy have abetter outcome. KEY WORDS: Ewing's sarcoma - Head and neck - Management.

AML1/ETO Fusion Gene in de novo Pediatric Acute Myeloid Leukemia: Clinical Significance and Prognostic Implications.

The characterization of leukemia-associated chromosome translocations has contributed relevant insights into our understanding of leukemia pathogenesis and has provided new specific tumor markers essential in prognostic assessment and minimal residual disease studies. The aim of this work is to study the frequency of AML1/ETO fusion gene in a series of Egyptian childhood AML cases. The clinical significance and prognostic implications of this aberration, including CR rate, duration of first CR, extramedullary leukemia (EML), and survival are investigated as well. Peripheral blood and/or bone marrow mononuclear cells were available for analysis from 78 children, all newly diagnosed with AML. AML1/ ETO fusion transcript was detected by the reverse transcriptase- polymerase chain reaction (RT-PCR) technique. Patients with de novo AML were treated by 2 courses of induction chemotherapy, followed by 4 courses of consolidation treatment if the patient achieved complete remission (CR). The marrow status was evaluated after each course in order to check bone marrow cellularity and presence of blasts. Patients with less than 5% blasts by the end of the second course of ADE passed to consolidation chemotherapy. Patients with more than 5% blasts by the end of the second course of ADE were excluded from the study. The AML1/ETO fusion transcript was detected by a singleround RT-PCR reaction and was found to be expressed in 15 out of 78 cases (19.2%). AML1/ETO positive patients were 7 girls and 8 boys, with ages ranging from 5 to 15 years. Seven cases (46.67%) belonged to FAB subtype M1, 7 (46.67%) M2, while only one case (6.67%) belonged to M5a subtype. Their total leukocytic counts ranged from 7.1 to 183.0 x 109/l with a median of 21.0 x 109/l. Their hemoglobin concentrations ranged from 4.8 to 10.3g/dl with a median of 7.4g/dl, while their platelet counts ranged from 6.0 to 96.0 x 109/l with a median of 25.5 x 109/l. Lymph nodes were enlarged in 8/15 cases (53.34%), hepatomegly was observed in 4/15 cases (26.67%), splenomegaly in 8/15 cases (53.34%), purpura in 6/15 cases (40%), while pallor was observed in all fifteen cases.Extramedullary leukemia occurred in 4/15 cases (26.67%). As regards the fate of the positive cases, thirteen cases (86.67%) attained complete remission (CR) following induction chemotherapy. Two patients (13.33%) died during induction in active disease. Eight patients were in complete continuous remission (CCR), four patients (26.67%) relapsed and died during relapse, and one patient (6.67%) died in complete remission due to severe neutropenia and infection. On comparing the AML1/ETO fusion gene status with overall survival, no significant difference was found between AML1/ETO positive and negative cases. Likewise, no difference could be found between positive and negative cases as regards disease-free survival (p=0.354). In conclusion, we report a frequency of 19.2% of AML1/ETO fusion gene in our newly diagnosed pediatric AML cases. Positive cases showed good response to induction therapy, as well as high complete remission rates, which are features of good prognosis. Key Words: Pediatric acute myeloid leukemia , AML1/ETO fusion gene , RT-PCR , Clinical outcome , Prognostic significance.