Mohamed Fawzy

Presence of Human Herpes Virus 6 (HHV6) in pediatric lymphomas: impact on clinical course and association with cytomegalovirus infection

BackgroundActivation of herpes virus 6 (HHV6) has seen in Hodgkins and non-Hodgkins Lymphoma (HL&NHL) as a result of lymphoma associated immunosuppression. Multiple studies have suggested an association between both HHV6 and cytomegalovirus CMV for development of CMV disease affecting the pathogenesis of lymphoma. Therefore, this study investigated the frequency of HHV6, its impact on clinical manifestations of lymphoma and its possible association with risk for development of CMV infection in pediatric lymphoma patients.MethodsPresence of HHV6 DNA and CMV DNA was investigated by PCR assay in both WBCs and plasma samples from 50 patients diagnosed with HL or NHL. CMV antibody titer was also determined in sera obtained from each patient. Twenty apparently healthy siblings were used as a control group.ResultsIn a study group of 50 patients diagnosed with HL or NHL, 23/50 (46%) were found to be positive for herpes virus DNA (HHV6 or CMV) in WBCs or plasma by PCR assay and this was significantly higher than its presence in the pediatric control group 2/20 (10%) (p = 0.005). Ten out of these 23 (43%) were found to have active CMV infection. Fifty six percent of patients with CMV infection were found among NHL cases with B- subtype. The presence of both herpes viruses DNA was significantly associated with more frequent episodes of febrile neutropenia (median 3 episodes), absolute neutrophil count (< 0.8), lymphocytes (< 0.5), and low hemoglobin level (< 9.1), (p < 0.05).ConclusionThe presence of HHV6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection which may result in a severe outcome among pediatric lymphoma patients.

Intraspinal neuroblastoma: Treatment options and neurological outcome of spinal cord compression

Malignant spinal cord compression (MSCC) is a common complication of cancer. Paraspinal neuroblastoma (NB) in the thoracic, abdominal and pelvic regions may extend into the neural foramina causing compression of nerve roots and even the spinal cord. The prompt initiation of specific treatment can improve the neurological outcome. The aim of the present study was to review the clinical features, the management received and the factors that may affect the outcome of patients with MSCC caused by paraspinal NB. During a period between July 2007 and December 2012, a total of 576 NB patients were treated at the Children’s Cancer Hospital (Cairo, Egypt). Intraspinal disease extension was present in 51 patients (9%). The children with intraspinal disease extension were reviewed for disease pattern, neurological manifestations and treatment outcome. Children with intraspinal disease extension had an equal male to female ratio (1:1), and approximately two-thirds of patients (34/51) had a clinically manifested cord compression. The duration of neurological manifestations was >4 weeks in 58.8% (20/34) of symptomatic patients and ≤4 weeks in 41.2% (14/34). Subsequent to starting treatment, neurological manifestations showed a complete recovery in 16 patients (47.1%), partial in 11 (32.4%), and stationary course was found in 7 (20.6%). Manifestations of ≤4 weeks in duration carried an improved outcome compared with longer time compression, with a complete recovery in 78.6%, versus 25% for patients with a longer symptom duration (P=0.008). The upfront treatment, patient age and site of the primary tumor did not significantly affect the neurological outcome. Spinal cord compression in NB can be effectively managed with upfront chemotherapy. Initial surgical decompression should be reserved for benign variants only, including ganglioneuroma. Neurological manifestations of <4 weeks duration upon presentation are usually reversible.

Role of Neuropilin-1 and its expression in Egyptian Acute Myeloid and Acute Lymphoid Leukemia patients

Neuropilins are expressed in tumors vasculature and cells. Their expression is thought to be correlated with tumor angiogenesis and progression. In this study, we analyzed NRP-1 expression level in 40 acute leukemia patients [20 acute myeloid leukemia (AML) and 20 acute lymphoblastic leukemia (ALL)] and 10 healthy controls using Real-Time Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RTQ-PCR) aiming to show Neuropilin-1 (NRP-1) gene expression pattern in acute leukemia patients and its role in disease severity and progression. NRP-1 was expressed in 80% and 95% of ALL and AML respectively with levels higher in patients than controls and in ALL than AML patients. NRP-1 levels were significantly correlated with blast percentage and complete remission. We conclude that NRP-1 is significantly associated with acute leukemia and that its level might serve as an indicator for disease severity and progression. NRP-1 signaling may represent a novel therapeutic approach for the treatment of acute leukemia subsets.

Assessment of hypotension during dialysis as a manifestation of myocardial ischemia in patients with chronic renal failure

Introduction: Intradialytic hypotension (IDH) remains to be a major complication of hemodialysis occurring in nearly 25% of dialysis sessions. It is a significant independent factor affecting mortality in hemodialysis patients. Autonomic nervous system dysfunction, blood sequestration in the setting of hypovolemia, cardiovascular diseases and increased plasma level of end products of nitric oxide metabolism are possible causes. In this controlled prospective study we examined patients with chronic renal failure and intradialytic hypotension to evaluate the relationship between this hypotension and myocardial ischemia after controlling other possible causes. Materials and methods: Thirty patients with chronic renal failure who are on regular dialysis were enrolled. Before dialysis, patients were subjected to history taking and clinical examination. Echocardiography and several lab tests were done. Glomerular filtration rate (GFR) was calculated using Cockcrofts and Gault formula. Autonomic dysfunction was also assessed. The dialysis session was standardized in all patients. Intradialytic blood pressure was monitored and hypotension was classified as mild (SBP > 100 mmHg), moderate (SBP 80–100) or severe (SBP < 80). After dialysis, myocardial ischemia was assessed using stress myocardial perfusion imaging (MPI) (Pharmacologic stress testing using Dipyridamole) and is further classified as mild, moderate or severe ischemia. Patients with sepsis, hemoglobin level less than 9 g/dL, diabetes mellitus, low cardiac output, coronary artery disease, significant valvular lesion or body weight below the dry weight of the patient were excluded from the study. Bronchial asthma, emphysema and severe COPD are contraindications to Dipyridamole and thus were also excluded from the study. Results: Twenty patients had no or mild intradialytic hypotension whereas ten patients had moderate or severe hypotension. Among the first group, only two patients (10%) were found to have myocardial ischemia, while in the latter group, seven patients (70%) had myocardial ischemia thats mostly moderate (p = 0.002). Stress induced LV dysfunction was also significantly prevalent in patients with moderate or severe intradialytic hypotension as opposed to other group (p = 0.002) LVED. Conclusions: Patients with CKD and regular hemodialysis who experience moderate or severe intradialytic hypotension have significantly higher prevalence of myocardial ischemia and stress induced myocardial dysfunction, than those who experience no or mild intradialytic hypotension.

Epstein-Barr virus and cytomegalovirus infections and their clinical relevance in Egyptian leukemic pediatric patients

BackgroundEpstein-Barr virus (EBV) and human cytomegalovirus (CMV) infections are environmental risk factors affecting the outcome of cancer due to an impairment in the cell-mediated immunity. Therefore, this study aimed to detect the frequency of EBV and CMV DNA and their association with clinical characteristics and outcome of pediatric leukemic patients.MethodsSamples of 50 immunocompromised pediatric leukemic patients and 30 apparently healthy children were subjected to the amplification of EBV DNA by one version of PCR targeting the Bam H1 W region of the genomic region of EBV, and the amplification of CMV DNA by targeting the CMV UL97 genomic region by a second round PCR. All investigations were performed on WBCs and sera. Results were correlated with the clinical and laboratory characteristics of the disease, and with overall survival.ResultsEBV and CMV DNA were detected in 20 and 54% of leukemic patients, respectively. Nine out of ten patients with EBV DNA (90%) were positive for CMV DNA in their sera. The presence of EBV DNA or CMV DNA was associated with neutropenia and a low total leukocyte count (TLC) (p = 0.02, 0.03, respectively). The presence of severe CMV disease, longer duration of febrile neutropenia, neutropenia, lymphopenia, thrombocytopenia and the presence of EBV DNA in patients’ sera were significantly associated with worse overall survival.ConclusionThe detection of CMV disease and EBV DNA is relatively common in leukemic children and is significantly associated with a decline in the overall survival.

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt

AIM The study aims to evaluate survival outcome in newly diagnosed pediatric intermediate risk neuroblastoma patients treated at the Children Cancer Hospital - Egypt and their relation to various clinical and pathological factors. METHODS The study included stage 3 patients <1.5 years, children 1.5 years or older with stage 3 disease and favorable histopathological features, infants (<1 year) with International Neuroblastoma Staging System (INSS) stage 4 disease, stage 4 children 1-1.5 years with favorable biology, and infants stage 4 s (with unfavorable biologic features). Patients received systemic chemotherapy, in the form of etoposide and carboplatin alternating with cyclophosphamide, doxorubicin and vincristine, administered at 3-week intervals, with a total of 6 or 8 cycles guided by reaching objective overall response (complete/very good partial/partial response). RESULTS The study included 136 patients, 67 males and 69 females. 101 patients had abdominal primary tumors, 28 had mediastinal masss and 7 with masses in the neck; 68% were stage 3 and the remaining (n = 44) had metastatic disease. The three-year overall survival (OS) and event-free survival (EFS) estimates were 94% ± 2% and 90.9% ± 2.5%, respectively. OS and EFS by gender, age, pathology and INPC were all statistically not significantly different. Moreover, OS for patients having surgery versus no surgery (inoperable residual only) was statistically significant (98.4% ± 1.6% & 88.7% ± 5.3%, respectively, p = .034). CONCLUSION A very high rate of survival is currently achievable in patients with intermediate risk neuroblastoma by chemotherapy or chemotherapy and surgery. In addition to response, our plan is to adopt biologically-based treatment to reduce treatment-induced complications among survivors.

Abstract 3991: Increased expression of cancer stem cells markers (CD44, CD90 and CD133) contributes to disease progression and reduced survival in hepatoblastoma patients from Egypt: four years survival data

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Hepatoblastoma (HB) is an embryonal tumor of the liver that occurs in infants and young children. Complete surgical resection and cisplatin-containing chemotherapy are crucial for cure in HB. Cancer stem cells (CSCs) constitute a newly identified subpopulation, which may differentiate into heterogeneous progenies of malignant cells. The aim of this study is to assess the prognostic and predictive values of CSCs markers (CD133, CD90 and CD44) in a cohort of HB patients from Egypt. Methods: Disease status was evaluated for 43 HB patients at the main checkpoints of therapy and during follow-up. Protein and RNA expressions of CD44, CD 90 and CD 133 were assessed by immunohistochemistry and quantitative real time (qPCR). Results: OS for all patients at 4 years was 58.2. OS significantly correlated with disease stages (stage II tumor response (p<0.001); CD44, CD 90, CD 133 expression (p<0.001) versus treatment modality (total surgical resection versus incomplete or no resection, 83.8% versus 25.2 %; p<0.001). Reduced DFS was associated with CD44 and CD133 expression (p<0.001) only. Conclusion: Complete surgical resection and systemic chemotherapy significantly improve outcome in HB with a significantly higher survival rates among patients with early stage disease. Expression of CSCs markers (CD133, 44, and 90) can predict poor outcome in HB patients with reduced OS and DFS rates. However further studies are required to confirm their prognostic and potential targeted therapy value. Citation Format: Abdel-Rahman N. Zekri, Abeer A. Bahnassy, Mohamed Fawzy, Mohamed El-Wakil, Ahmed Abdel-Sayed, Marwa E. Sheta. Increased expression of cancer stem cells markers (CD44, CD90 and CD133) contributes to disease progression and reduced survival in hepatoblastoma patients from Egypt: four years survival data. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3991. doi:10.1158/1538-7445.AM2014-3991