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Ali, N., M. Selim, Z. Salah, N. M. El Nabarawy, H. Hussein, and I. Sidhom, "Cardiovascular and Thyroid Late Effects in Pediatric Patients With Hodgkin Lymphoma Treated With ABVD Protocol.", Journal of pediatric hematology/oncology, vol. 45, issue 4, pp. e455-e463, 2023. Abstract

BACKGROUND: Hodgkin lymphoma (HL) survivors are at risk of developing a range of therapy-related complications. The goal of this study is to investigate therapy-related late-effects in HL survivors.

MATERIALS AND METHODS: We performed a cross-sectional study on 208 HL survivors who were treated at the National Cancer Institute or at the Children Cancer Hospital Egypt with doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy.

RESULTS: Age at diagnosis ranged from 2.5 to 17.5 with a median of 8.7 years. The cumulative incidence of cardiac toxicity at 5 and 9 years were 18.7%±2.7% and 43.3%±4.4%, respectively. Preexisting cardiac abnormalities, cumulative anthracycline dose, and end of treatment cardiac status are strong predictors of late cardiotoxicity. Hypertension was observed in ~31% of patients. Young age and obesity at the time of treatment are important risk factors for hypertension. Thyroid abnormalities developed with a 5-year cumulative incidence of 2%±1%, whereas at 9 years the cumulative incidence was 27.9%±4.5%. Thyroid dysfunction was observed in 21.2% and thyroid tumors in 1.6% of cases. Subclinical hypothyroidism was the most common thyroid abnormality.

CONCLUSIONS: Cardiotoxicity, hypertension, and thyroid dysfunction are frequent late effects after doxorubicin, bleomycin, vinblastine, and dacarbazine regimen, especially if combined with radiation therapy.

Soliman, R., J. Oke, I. Sidhom, N. Bhakta, N. S. Bolous, N. Tarek, S. Ahmed, H. A. Rahman, E. Moussa, M. Zamzam, et al., "Cost-effectiveness of childhood cancer treatment in Egypt: Lessons to promote high-value care in a resource-limited setting based on real-world evidence.", EClinicalMedicine, vol. 55, pp. 101729, 2023. Abstract

BACKGROUND: Childhood cancer in low-and middle-income countries is a global health priority, however, the perception that treatment is unaffordable has potentially led to scarce investment in resources, contributing to inferior survival. In this study, we analysed real-world data about the cost-effectiveness of treating 8886 children with cancer at a large resource-limited paediatric oncology setting in Egypt, between 2013 and 2017, stratified by cancer type, stage/risk, and disease status.

METHODS: Childhood cancer costs (USD 2019) were calculated from a health-system perspective, and 5-year overall survival was used to represent clinical effectiveness. We estimated cost-effectiveness as the cost per disability-adjusted life-year (cost/DALY) averted, adjusted for utility decrement for late-effect morbidity and mortality.

FINDINGS: For all cancers combined, cost/DALY averted was $1384 (0.5 × GDP/capita), which is very cost-effective according to WHO-CHOICE thresholds. Ratio of cost/DALY averted to GDP/capita varied by cancer type/sub-type and disease severity (range: 0.1-1.6), where it was lowest for Hodgkin lymphoma, and retinoblastoma, and highest for high-risk acute leukaemia, and high-risk neuroblastoma. Treatment was cost-effective (ratio <3 × GDP/capita) for all cancer types/subtypes and risk/stage groups, except for relapsed/refractory acute leukaemia, and relapsed/progressive patients with brain tumours, hepatoblastoma, Ewing sarcoma, and neuroblastoma. Treatment cost-effectiveness was affected by the high costs and inferior survival of advanced-stage/high-risk and relapsed/progressive cancers.

INTERPRETATION: Childhood cancer treatment is cost-effective in a resource-limited setting in Egypt, except for some relapsed/progressive cancer groups. We present evidence-based recommendations and lessons to promote high-value in care delivery, with implications on practice and policy.

FUNDING: Egypt Cancer Network; NIHR School for Primary Care Research; ALSAC.

Mahdy, A., asmaa hamoda, A. Zaher, E. Khorshed, M. Elwakeel, O. Hassanein, and I. Sidhom, "Outcome and toxicity of ifosfamide, carboplatin, and etoposide versus gemcitabine and vinorelbine regimen for pediatric patients with relapsed or refractory Hodgkin's lymphoma.", Frontiers in oncology, vol. 13, pp. 1153128, 2023. Abstract

BACKGROUND: Pediatric classical Hodgkin lymphoma (CHL) is a curable disease; however, the optimal salvage regimen is unclear for relapsed/refractory (R/R) disease. This study aimed to compare response rates, toxicity, event-free survival (EFS), and overall survival (OS) of ifosfamide, carboplatin, and etoposide (ICE) with gemcitabine and vinorelbine (GV) regimen after first-line doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) in pediatric patients with R/R CHL.

METHODS: This is a retrospective cohort study of 132 pediatric patients with R/R CHL treated from July 2012 to December 2020 with ICE (n = 82) or GV (n = 50).

RESULTS: The median age at relapse was 13.9 years, and 68.2% were men. Rates of complete response, partial response, and progressive disease before consolidation were 50.6%, 3.7%, and 45.7% for ICE and 28.5%, 0%, and 71.5% for GV (P = 0.011). By multivariate analysis, regimen (P = 0.002), time to relapse (P = 0.0001), and B-symptoms (P = 0.002) were independent factors to lower response rates. Hematological toxicity, electrolyte disturbance, hemorrhagic cystitis, infectious complications, and hospital admission for fever neutropenia were statistically significant higher for the ICE regimen. Treatment-related mortalities were 2.4% for ICE and 2% for GV (P = 0.86). The 3-year EFS was 39.3% ± 11.4% for ICE and 24.9% ± 12.5% for GV (P = 0.0001), while 3-year OS was 69.3% ± 10.6% and 74% ± 12.9% (P = 0.3), respectively. By multivariate analysis, regimen (P = 0.0001), time to relapse (P = 0.011), B-symptoms (P = 0.001), and leukocytosis (P = 0.007) were significant for EFS, while anemia (P = 0.008), and progressive disease on early response evaluation (P = 0.022) were significant for OS.

CONCLUSIONS: The ICE regimen had a better overall response rate and EFS, but higher toxicity, than GV; however, OS and mortality were similar.

Younes, A., M. F. Taher, I. Sidhom, W. Zekri, I. Zaky, H. Elfendy, A. N. Taher, S. A. Khedr, R. Gamal, and G. Ahmed, "Parotid gland masses: outcomes in the pediatric age group.", Journal of the Egyptian National Cancer Institute, vol. 35, issue 1, pp. 2, 2023. Abstract

BACKGROUND: Childhood parotid neoplasms appear to have different characteristics from adults. This point, in addition to the rarity of these tumors, reflects the challenges faced in diagnosing and treating parotid neoplasms in children.

PATIENTS AND METHODS: This retrospective study included all children who presented to the Children's Cancer Hospital Egypt (CCHE, 57357) with parotid masses from January 2008 to December 2020.

RESULTS: Twenty-one patients were included. Malignant neoplasms were found in 12 (57.1%) of which mucoepidermoid carcinoma was the most common. Benign neoplasms were found in 6 (28.6%) all of them were pleomorphic adenoma, and non-neoplastic lesions were found in 3 (14.3%). Superficial, deep, or total parotidectomy was performed according to the involved lobes. The facial nerve was sacrificed in three cases because of frank invasion by the tumor. Neck dissection was considered in clinically positive lymph nodes and/or T3/4 masses. Complications occurred in 7 (33.3%) all were of the malignant cases. Adjuvant radiotherapy was restricted to high-risk cases (7 cases). Recurrence occurred in two cases, and one patient died of distant metastasis. Fine needle aspiration cytology (FNAC) showed 88.9% sensitivity and 100% specificity for diagnosing malignant neoplasms. The correlation of radiological and pathological staging was fair (66.74% for overall staging).

CONCLUSIONS: Parotidectomy is the backbone treatment for benign and malignant pediatric parotid tumors. Neck nodal dissection should be considered after preoperative FNAC of suspicious nodes. Adjuvant radiotherapy is considered only in high-risk tumors. Preoperative FNAC of parotid masses and clinically suspicious lymph nodes is highly recommended.

Salama, M., S. Ahmed, S. Soliman, N. El-Sharkawy, S. Salem, A. El-Nashar, R. Khedr, L. Lehmann, I. Sidhom, and A. El-Haddad, "Characteristics, Treatment Complexity, and Outcome of Mixed-Phenotype Acute Leukemia in Children in a Low-Middle-Income Country.", Frontiers in oncology, vol. 12, pp. 941885, 2022. Abstract

BACKGROUND: Mixed-phenotype acute leukemia (MPAL) in children is an uncommon subtype of acute leukemia that cannot be definitively assigned to a specific lineage. There is no consensus on the best approach to therapy. Management is more complex in low-middle-income countries (LMICs).

AIM: To evaluate the clinicopathological characteristics and outcomes of patients with MPAL in a developing country.

PATIENTS AND METHODS: A retrospective descriptive study of 42 pediatric patients newly diagnosed with MPAL from July 2007 until December 2017.

RESULTS: The immunophenotyping was T/Myeloid in 24 patients (57.1%) and B/Myeloid in 16 (38.1%). Three subjects had gene rearrangement, two had chromosomes, and eight had internal tandem duplication (FLT3-ITD) with a ratio >0.4. Two subjects died before starting chemotherapy. Ten patients (25%) received acute lymphoblastic leukemia (ALL) induction, and all achieved complete remission (CR) with no induction deaths and no shift of therapy. Thirty patients (75%) started therapy with acute myeloid leukemia (AML) induction: five (16.6%) died during induction, 17 (56.7%) achieved CR, and 10 patients received maintenance ALL therapy after ending AML treatment. Four of the eight patients with induction failure were switched to ALL therapy. The 5-year event-free survival (EFS) and overall survival (OS) rates were 56.7% [standard error (SE): 8.1%] and 61% (SE: 8%), while the cumulative incidence of relapse was 21.7% (SE: 6.7%), with a median follow-up duration of 5.8 years. Patients treated with ALL-directed therapy had a 5-year EFS rate of 111 70% (SE: 14%) and OS rate of 78.8% (SE: 13%). Patients treated with ALL-directed therapy had a 5-year EFS rate of 70% (SE: 14.5%) and OS rate of 78.8% (SE: 13%). mutation showed a significantly lower 5-year EFS rate of 28.6% (SE: 17%) vs. 75% (SE: 9%) for the wild type, p = 0.032. Undernourished patients with a body mass index (BMI) -score ≤-2 at presentation had a significantly lower 5-year EFS rate of 20% (SE: 17%) compared to 61.8% (SE: 8%) for patients with BMI -score >-2, p = 0.015.

CONCLUSION: This study supports ALL-directed therapy for pediatric MPAL in a setting of LMIC. Given the poor outcome of , the role of inhibitor needs to be explored in this subset of cases.

Hammad, M., H. Hafez, I. Sidhom, D. Yassin, S. Salem, K. Alsheshtawi, N. hamdy, N. ElSharkawy, and A. Elhaddad, "Hematopoietic stem cell transplantation from HLA-matched sibling donors in children with acute lymphoblastic leukemia: A report from the Children's Cancer Hospital Egypt.", Frontiers in oncology, vol. 12, pp. 983220, 2022. Abstract

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (HSCT) is widely used for high-risk acute lymphoblastic leukemia (ALL) patients in their first complete remission (CR1), and for relapsed patients in second complete remission (CR2).

PATIENTS AND METHODS: We retrospectively analyzed data for 67 children with ALL, from a cancer center in a low/middle income country, who had undergone HSCT from human leukocyte antigen (HLA)-matched sibling donors (MSDs) using myeloablative conditioning (MAC) regimens, between 2007 and 2020, describing the survival outcome and relapse probability after achieving CR1 and CR2 and determining outcome differences in relation to indications for HSCT in patients transplanted in CR1. All patients had achieved a negative minimal residual disease prior to transplant (<0.01%).

RESULTS: Forty-six patients (68.7%) were in CR1; 25 had adverse cytogenetics, including 18 patients with Philadelphia chromosome-positive ALL (Ph-positive ALL), and 21 had poor induction response. The 5-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) for the whole cohort were 56.1% (95% CI, 42.8%-69.4%), 49% (95% CI, 35.7%-62.3%) and 33.5% (95% CI, 21.7%-45.8%), respectively with better EFS and CIR for CR1 transplants compared to CR2 transplants (P=0.02 and P=0.03, respectively). Patients with Ph-positive ALL had better 5-year OS, EFS and non-relapse mortality (NRM) compared with other CR1 transplants (P=0.015, P=0.009 and P=0.028, respectively).

CONCLUSION: Hematopoietic stem cell transplantation from MSD for ALL in CR1 group had superior outcomes compared to CR2 group and was apparently a curable option for Ph-positive ALL without an increased risk of non-relapse mortality. Poorer survival rates and higher relapse probabilities were associated with HSCT conducted to patients who had a poor response to induction therapy or suffered a relapse.

Soliman, R., C. Heneghan, N. S. Bolous, I. Sidhom, S. Ahmed, N. Roberts, J. Oke, and A. Elhaddad, "Systematic review of costs and cost-effectiveness of treatment for relapsed/refractory acute leukemia in children and young adults.", Expert review of hematology, vol. 15, issue 4, pp. 345-357, 2022. Abstract

INTRODUCTION: Survival outcomes of children with relapsed/refractory (r/r) acute leukemia remain poor. Novel expensive treatments have been developed to improve their outcomes, yet, limited evidence exists about cost-effectiveness of alternative treatment strategies.

AREAS COVERED: A systematic review was conducted to summarize health-economic evidence about costs/cost-effectiveness of treating r/r acute leukemia in children/young adults. We searched Medline, Embase, and Cochrane databases until August 13th, 2021. Eligible articles included peer-reviewed original studies addressing r/r pediatric/young-adult acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Quality assessment was conducted using Consolidated Health Economics Evaluation Reporting Standards (CHEERS) checklist.

EXPERT OPINION: The majority of papers focused on CAR-T cell therapy, which is still a novel treatment for r/r ALL, and was found to be cost-effective, yet, there remain concerns over its long-term effectiveness, affordability, and equity in access. The next best treatment option is Blinatumomab, followed by Clofarabine therapy, whereas FLA-IDA salvage chemotherapy provides least value for money. The quality of evidence is moderate to high, with limited generalizability of findings due to high variability in outcomes obtained from modeling studies. Limited studies evaluated r/r AML. We provide recommendations to deliver cost-effective treatments in real-world contexts, with implications for healthcare policy and practice.

Hammad, M., L. Shalaby, I. Sidhom, N. Sherief, I. Abdo, S. Soliman, Y. Madeny, R. Hassan, S. Elmeniawy, N. Khamis, et al., "Management and Outcome of Coronavirus Disease 2019 (COVID-19) in Pediatric Cancer Patients: A Single Centre Experience from a Developing Country.", Clinical lymphoma, myeloma & leukemia, vol. 21, issue 11, pp. e853-e864, 2021. Abstract

INTRODUCTION: Sufficient data pertaining to the impact of the Coronavirus disease 2019 (COVID-19) on pediatric cancer patients is still lacking. The aim of this prospective study was to describe clinical management and outcomes of COVID-19 in pediatric oncology patients.

PATIENTS AND METHODS: Conducted between May 1, 2020 and November 30, 2020, this study included 76 pediatric oncology patients with confirmed COVID-19. Remdesivir (RDV) was the antiviral therapy used.

RESULTS: The median age of patients was 9 years. Sixty patients were on first line treatment. Hematological malignancies constituted 86.8% of patients. Severe to critical infections were 35.4% of patients. The commonest symptom was fever (93.4%). Chemotherapy was delayed in 59.2% of patients and doses were modified in 30.2%. The 60-day overall survival (OS) stood at 86.8%, with mortalities occurring only among critical patients. Of sixteen acute leukemia patients in the first induction therapy, 13 survived and 10 achieved complete remission. A negative RT-PCR within 2 weeks and improvement of radiological findings were statistically related to disease severity (P = .008 and .002, respectively). Better OS was associated with regression of radiological findings after 30 days from infection (P = .002). Forty-five patients received RDV, 42.1% had severe and critical forms of infection compared to 25.7% in the No-RDV group and yet OS was comparable in both groups.

CONCLUSION: Most pediatric cancer patients with COVID-19 should have good clinical outcomes except for patients with critical infections. Cancer patients can tolerate chemotherapy including induction phase, alongside COVID-19 treatment. In severe and critical COVID-19, RDV might have a potential benefit.

Hafez, H. A., I. Ragab, M. Sedky, M. Shams, A. Youssef, A. Refaat, E. Habib, and I. Sidhom, "Patterns, risk factors and outcome predictors of posterior reversible encephalopathy syndrome in pediatric cancer patients.", Leukemia & lymphoma, vol. 62, issue 2, pp. 462-468, 2021. Abstract

The purpose of this study was to assess the clinical and radiological patterns and outcome predictors of posterior reversible encephalopathy syndrome (PRES) in pediatric cancer patients. A retrospective study included patients who developed PRES during their treatment at the Children's Cancer Hospital Egypt. A total of 50 patients developed PRES. Leukemia and lymphoma were the commonest diagnoses (64%). Regarding the MRI findings, occipital affection was the most common (92%), followed by frontal and temporal lobes involvement in 32% and 22% respectively and advanced PRES was described in 8 patients. Of the whole patients, 80% had complete clinical resolution and 60% showed complete radiological resolution at 2 weeks' evaluation and 2 patients died out of PRES. Unfavorable outcome was associated with those who had motor dysfunction, status epilepticus at presentation, frontal lobe and thalamic affection and atypical PRES. PRES might present in atypical sites with poor outcome including death.

Sidhom, I., K. Shaaban, S. H. Youssef, N. Ali, S. Gohar, W. M. Rashed, M. Mehanna, S. Salem, S. Soliman, D. Yassin, et al., "Reduced-intensity therapy for pediatric lymphoblastic leukemia: impact of residual disease early in remission induction.", Blood, vol. 137, issue 1, pp. 20-28, 2021. Abstract

Legacy data show that ∼40% of children with acute lymphoblastic leukemia (ALL) were cured with limited antimetabolite-based chemotherapy regimens. However, identifying patients with very-low-risk (VLR) ALL remains imprecise. Patients selected based on a combination of presenting features and a minimal residual disease (MRD) level <0.01% on day 19 of induction therapy had excellent outcomes with low-intensity treatment. We investigated the impact of MRD levels between 0.001% and <0.01% early in remission induction on the outcome of VLR ALL treated with a low-intensity regimen. Between October of 2011 and September of 2015, 200 consecutive patients with B-precursor ALL with favorable clinicopathologic features and MRD levels <0.01%, as assessed by flow cytometry in the bone marrow on day 19 and at the end of induction therapy, received reduced-intensity therapy. The 5-year event-free survival was 89.5% (± 2.2% standard error [SE]), and the overall survival was 95.5% (± 1.5% SE). The 5-year cumulative incidence of relapse (CIR) was 7% (95% confidence interval, 4-11%). MRD levels were between 0.001% and <0.01% on day 19 in 29 patients. These patients had a 5-year CIR that was significantly higher than that of patients with undetectable residual leukemia (17.2% ± 7.2% vs 5.3% ± 1.7%, respectively; P = .02). Our study shows that children with VLR ALL can be treated successfully with decreased-intensity therapy, and it suggests that the classification criteria for VLR can be further refined by using a more sensitive MRD assay.

Soliman, R. M., A. Elhaddad, J. Oke, W. Eweida, I. Sidhom, S. Ahmed, H. A. Rahman, E. Moussa, M. O. H. A. M. E. D. FAWZY, M. Zamzam, et al., "Temporal trends in childhood cancer survival in Egypt, 2007 to 2017: A large retrospective study of 14 808 children with cancer from the Children's Cancer Hospital Egypt.", International journal of cancer, vol. 148, issue 7, pp. 1562-1574, 2021. Abstract

Childhood cancer is a priority in Egypt due to large numbers of children with cancer, suboptimal care and insufficient resources. It is difficult to evaluate progress in survival because of paucity of data in National Cancer Registry. In this study, we studied survival rates and trends in survival of the largest available cohort of children with cancer (n = 15 779, aged 0-18 years) from Egypt between 2007 and 2017, treated at Children's Cancer Hospital Egypt-(CCHE), representing 40% to 50% of all childhood cancers across Egypt. We estimated 5-year overall survival (OS) for 14 808 eligible patients using Kaplan-Meier method, and determined survival trends using Cox regression by single year of diagnosis and by diagnosis periods. We compared age-standardized rates to international benchmarks in England and the United States, identified cancers with inferior survival and provided recommendations for improvement. Five-year OS was 72.1% (95% CI 71.3-72.9) for all cancers combined, and survival trends increased significantly by single year of diagnosis (P < .001) and by calendar periods from 69.6% to 74.2% (P < .0001) between 2007-2012 and 2013-2017. Survival trends improved significantly for leukemias, lymphomas, CNS tumors, neuroblastoma, hepatoblastoma and Ewing Sarcoma. Survival was significantly lower by 9% and 11.2% (P < .001) than England and the United States, respectively. Significantly inferior survival was observed for the majority of cancers. Although survival trends are improving for childhood cancers in Egypt/CCHE, survival is still inferior in high-income countries. We provide evidence-based recommendations to improve survival in Egypt by reflecting on current obstacles in care, with further implications on practice and policy.

Ali, N., S. Gohar, I. Zaky, AhmedElghoneimy, S. Youssef, G. Sameer, D. Yassin, S. Salem, H. Magdi, and I. Sidhom, "Osteonecrosis in children with acute lymphoblastic leukemia: A report from Children's Cancer Hospital Egypt (CCHE).", Pediatric blood & cancer, vol. 66, issue 1, pp. e27440, 2019. Abstract

BACKGROUND: As survival rates for children with acute lymphoblastic leukemia (ALL) improve, awareness of treatment complications becomes important. Osteonecrosis (ON) is a serious disabling complication in treated ALL patients. The aim of the study was to define the frequency of ON identified by magnetic resonance imaging (MRI) and to study the risk factors for ON.

PATIENTS AND METHODS: The frequency of ON was evaluated retrospectively in 858 patients with ALL who were diagnosed at Children's Cancer Hospital of Egypt from January 2009 to December 2012. Patients were treated with St Jude Total Therapy Study XV.

RESULTS: Of 858 patients evaluated, 665 were eligible for the study and 65 (9.7%) developed ON. The cumulative 5-year incidence of ON was 11.96% (SE, 0.131%). Of 154 patients aged 10 years and older, 40 (26%) developed ON. The mean age of patients with ON was 10.7 years. The prognostic factors with a significant relationship with ON were age 10 years and older (P = 0.0001) and intermediate-/high-risk group (P = 0.0001). However, gender did not have a significant relationship. At the onset of ON, the mean cumulative dexamethasone dose was 796 mg/m , and the mean total corticosteroid dose, calculated as prednisolone equivalence, was 6,431 mg/m . Out of 43 patients who developed ON while on corticosteroid therapy, 36 (84%) required dexamethasone dose modification and/or discontinuation.

CONCLUSION: The frequency of ON among the studied patients was 9.7%. Risk factors with a significant association with ON were older age and more intensive corticosteroid therapy.

Elharouni, D., D. Yassin, N. Ali, S. Gohar, I. Zaky, H. Adwan, and I. Sidhom, "A Pharmacogenetic Study of VDR fok1 and TYMS Polymorphisms and Their Association With Glucocorticoid-Induced Osteonecrosis in Egyptian Children With Acute Lymphoblastic Leukemia.", Frontiers in oncology, vol. 8, pp. 541, 2018. Abstract

Osteonecrosis is a significant toxicity resulting from the treatment of pediatric Acute Lymphoblastic Leukemia (ALL). This study aimed to investigate the relationship between vitamin D receptor fok1 (VDR fok1) and thymidylate synthase (TYMS) gene polymorphisms with the glucocorticoid (GC) induced osteonecrosis (ON) in Egyptian pediatric ALL patients. In addition, to identify the possible association of genetic polymorphisms with other factors such as gender and ALL subtypes. A retrospective case-control study was conducted on 102 pediatric ALL patients under the age of 18 who were treated at Children Cancer Hospital Egypt according to St Jude SR/HR total XV protocol. The recruited patients were composed of 51 cases who developed GC-induced osteonecrosis and 51 age- and gender-matched patients who received glucocorticoids but remained osteonecrosis-free (controls). Genotyping of the VDR fok1 and TYMS genes was performed using restriction fragment length polymorphism (RFLP) and conventional PCR, respectively. For the total 102 studied patients, the VDR fok1 single nucleotide polymorphisms (SNPs) frequency distribution were TT (8.8%), CT (34.3%), and CC (56.9%), while the TYMS tandem repeat gene variations were reported as 2R2R (20.6%), 2R3R (45.1%), and 3R3R (34.3%). VDR fok1 and TYMS polymorphic variants showed no association neither with gender; -values 0.3808 and 0.1503, respectively, nor with ALL subtypes; -values 0.9396 and 0.6596, respectively. The VDR fok1 polymorphisms showed a significant association with the development of ON; -value = 0.003, on the other hand, TYMS tandem repeats did not show significant impact on osteonecrosis development; -value = 0.411. This study showed a significant association between the VDR fok1 polymorphism and osteonecrosis. Such clinical pharmacogenetics results would be promising to discuss the possibility of dose adjustments aiming a regimen with the highest efficacy and least toxicity.

Ezzat, S., W. M. Rashed, S. Salem, T. M. Dorak, M. El-Daly, M. Abdel-Hamid, I. Sidhom, A. Elhaddad, and C. Loffredo, "Environmental, maternal, and reproductive risk factors for childhood acute lymphoblastic leukemia in Egypt: a case-control study", BMC Cancer, vol. 16, pp. 662 , 2016.
Moussa, H., and I. Sidhom, "NKX2-5, SIL/TAL and TLX3/HOX11L2 expression in Egyptian pediatric T-cell acute lymphoblastic leukemia.", Asia-Pacific journal of clinical oncology, vol. 12, issue 1, pp. e1-10, 2016. Abstract

AIM: Cohorts of T-cell acute lymphoblastic leukemia (T-ALL) patients show regional geographic differences in incidence, biological features and clinical outcome, implying that in different populations, cases may harbor different genetic lesions than those reported elsewhere. In this study, we prospectively evaluated the frequency and the clinical relevance of NKX2-5, TLX3/HOX11L2 and SIL/TAL expression in Egyptian childhood T-ALL.

METHODS: NKX2-5, TLX3/HOX11L2 and SIL/TAL expression were tested in peripheral blood and/or bone marrow of 83 newly diagnosed Egyptian childhood T-ALL patients.

RESULTS: NKX2-5 expression was detected in 11/83 cases (13%), TLX3/HOX11L2 (5/83, 6%) and SIL/TAL (4/83, 5%). Initial central nervous system involvement was significantly higher in the NKX2-5 positive versus negative patients (P = 0.009). The follow-up period was a median of 65.5 months. The 5-year leukemia-free and event-free survival rates of the whole T-ALL population were 70 ± 6% and 58 ± 6%, respectively. The 5-year leukemia-free and event-free survival rates of NKX2-5 were 86 ± 13% and 60 ± 16%, respectively. There were no statistically significant differences in clinical presentation, biological features, initial response to chemotherapy, or subsequent treatments between the subgroups and the total population.

CONCLUSION: Egyptian T-ALL cases seemed to have a different genetic pattern compared to other populations, with a lower incidence of TLX3/HOX11L2 and SIL/TAL but a higher incidence of NKX2-5 expression than recorded in Western countries.

Sidhom, I., E. E. Nadi, H. Taha, N. elkinaai, M. S. Zaghloul, A. Younes, R. Labib, and M. Sabry, "Clinical Significance of Anaplasia in Childhood Rhabdomyosarcoma.", Journal of the Egyptian National Cancer Institute , vol. 27, issue 2, pp. 83-89, 2015.
Gamal T Ebid, I. A. Sedhom, M. M. El-Gammal, and M. M. Moneer, "MDM2 T309G has a synergistic effect with P21 ser31arg single nucleotide polymorphisms on the risk of acute myeloid leukemia.", Asian Pacific journal of cancer prevention : APJCP, vol. 13, issue 9, pp. 4315-20, 2012. Abstract

BACKGROUND: The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis.

AIM OF THE STUDY: We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk.

RESULTS: We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR= 6.807, 95% CI= 1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value= 0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML.

CONCLUSION: We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/ MDM2 might be genetic susceptibility factors in the pathogenesis of AML.

Riad, R., W. Omar, I. Sidhom, M. Zamzam, I. Zaky, M. Hafez, and H. Abdel-Dayem, "False-positive F-18 FDG uptake in PET/CT studies in pediatric patients with abdominal Burkitt's lymphoma", Nuclear medicine communications, vol. 31, issue 3, pp. 232-238, 2010.
Riad, R., W. Omar, M. Kotb, M. Hafez, I. Sidhom, M. Zamzam, I. Zaky, and H. Abdel-Dayem, "Role of PET/CT in malignant pediatric lymphoma", European journal of nuclear medicine and molecular imaging, vol. 37, issue 2, pp. 319-329, 2010.
Sidhom, I., K. Shaaban, S. Soliman, S. Ezzat, W. El-Anwar, N. hamdy, D. Yassin, S. Salem, H. Hassanein, and M. T. Mansour, "Clinical significance of immunophenotypic markers in pediatric T-cell acute lymphoblastic leukemia.", Journal of the Egyptian National Cancer Institute, vol. 20, issue 2, pp. 111-20, 2008. Abstract

BACKGROUND: Cell-marker profiling has led to conflicting conclusions about its prognostic significance in T-ALL.

AIM: To investigate the prevalence of the expression of CD34, CD10 and myeloid associated antigens (CD13/ CD33) in childhood T-ALL and to relate their presence to initial clinical and biologic features and early response to therapy.

PATIENTS AND METHODS: This study included 67 consecutive patients with newly diagnosed T-ALL recruited from the Children's Cancer Hospital in Egypt during the time period from July 2007 to June 2008. Immunophenotypic markers and minimal residual disease (MRD) were studied by five-color flow cytometry.

RESULTS: The frequency of CD34 was 34.9% , CD10 33.3% , while CD13/CD33 was 18.8%. No significant association was encountered between CD34, CD10 or myeloid antigen positivity and the presenting clinical features as age, sex, TLC and CNS leukemia. Only CD10(+) expression had significant association with initial CNS involvement (p=0.039). CD34 and CD13/CD33 expression was significantly associated with T-cell maturation stages (p<0.05). No relationship was observed for age, TLC, gender, NCI risk or CNS involvement with early response to therapy illustrated by BM as well as MRD day 15 and day 42. CD34(+), CD13/CD33(+) and early T-cell stage had high MRD levels on day 15 that was statistically highly significant (p<0.01), but CD10(+) had statistically significant lower MRD level on day 15 (p=0.049). However, only CD34 retained its significance at an MRD cut-off level of 0.01%.

CONCLUSIONS: CD34, CD10, CD13/CD33 expression, as well as T-cell maturation stages, may have prognostic significance in pediatric T-ALL as they have a significant impact on early clearance of leukemic cells detected by MRD day 15.

El-Badawy, S., S. Aboul Naga, A. Abou Gabal, A. Mokhless, M. Zamzam, I. Sidhom, E. Ebeid, and H. Hussein, "Risk adapted combined modality treatment in children with Hodgkin's disease: NCI, Cairo.", Journal of the Egyptian National Cancer Institute, vol. 20, issue 2, pp. 99-110, 2008. Abstract

OBJECTIVE: The objective of this study is to maximize the chance of cure while minimizing surgery, radiotherapy and chemotherapy as much as possible to avoid late effects and toxicity of combined modality treatment in children with Hodgkin's disease.

PATIENTS AND METHODS: One hundred twenty-one (121) children under the age of 18 years with a histopathologic diagnosis of Hodgkin's disease were enrolled into this study. Patients were stratified according to stage into 3 risk groups: low (Stages: I, II A), intermediate (Stages: II B, III A) and high risk group (Stages: III B, IV). Oral Etoposide was used in this study instead of procarbazine in the management of boys with HD to reduce the gonadotoxic effects of procarbazine. Two cycles of OPPA for females and E-OPA for males were effective induction treatment for children with all stages of HD and stage-tailored chemotherapy (2, 4, 6 cycles of OPPA, E-OPA/ COPP) was sufficient to eradicate occult microfoci. Involved field radiotherapy was given in doses of 30, 25, 20 Gy, depending on the extent of initial chemotherapy and risk status. Staging laparotomy was performed in 30 patients out of the 121 patients, 24 of them underwent splenectomy. Patients who received whole neck radiotherapy were submitted to thyroid U/S and thyroid hormonal profile. Only 3 adolescent patients did semen analysis.

RESULTS: The overall and disease-free survival rates at 6 years were 95.3% and 86.1% (95% CI), respectively (entire group), 96.1% , 92.3% (95% CI) for low risk, 96.1% , 80.7% (95% CI) for intermediate risk and 93.3% , 80% (95% CI) for high risk patients. During the followup period all patients had normal thyroid functions.

CONCLUSIONS: In children with HD, only low dose involved field radiotherapy with reduced doses is needed,if a risk-dependent chemotherapy is given. In this series the strategy of selective laparotomy and restrictive splenectomy is very useful in the context of combined modality treatment, in which laparotomy was omitted if both abdominal U/S and CT were negative.

HAMOUDA, F., A. EL-SISSY, A. Radwan, H. Hussein, F. Gadallah, N. AL-SHARKAWY, I. Sidhom, E. Ebeid, S. Salem, and A. Kamel, "Correlation of Karyotype and Immunophenotype in Childhood Acute Lymphoblastic Leukemia; Experience at the National Cancer Institute, Cairo University, Egypt", Journal of the Egyptian Nat. Cancer Inst., , vol. 2, issue 19, pp. 87-95, 2007.
El-Mahallawy, H., I. Sidhom, A. N. H. El-Din, M. Zamzam, and M. M. El-Lamie, "Clinical and microbiologic determinants of serious bloodstream infections in Egyptian pediatric cancer patients: a one-year study.", International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, vol. 9, issue 1, pp. 43-51, 2005. Abstract

OBJECTIVES: Bloodstream infections (BSI) remain a major cause of morbidity and death in patients undergoing treatment for cancer. However, all recent epidemiological and therapeutic studies underline the absolute need for knowledge of the factors governing the infections in each center. The aim of this study is to identify the factors affecting BSI in the pediatric service of the National Cancer Institute (NCI) at Cairo University. More tailored policies for the treatment of patients with febrile neutropenia following chemotherapy can then be created.

PATIENTS AND METHODS: Over a 12-month period, all children with cancer and fever, with or without neutropenia, who were admitted to the NCI for empirical therapy of febrile episodes and who had a microbiologically confirmed bloodstream infection were studied retrospectively.

RESULTS: A total of 328 BSI occurred in 1135 febrile episodes in pediatric cancer patients at the NCI in one year. Gram-positive bacteria were isolated in 168 episodes (51.2%) and 61.9% of the total isolates (either single or mixed), Gram-negative in 97 (29.6%), and mixed infections in 45 (13.7%). The common causative agents of bloodstream infections in this study were coagulase-negative staphylococci (16.2%), Staphylococcus aureus (13.4%), Streptococcus spp. (12.1%) followed by Acinetobacter spp. (6.7%) and Pseudomonas spp. (5.5%). Fungemia was encountered in 18 episodes, being mixed in nine of them. A more serious BSI in terms of a prolonged episode was encountered in 30.2% of the episodes and was significantly associated with patients being hospitalized, having intensified chemotherapy, polymicrobial and fungal infection, lower respiratory tract infections and persistent neutropenia at day seven.

CONCLUSIONS: In a large population of children, common clinical and laboratory risk factors were identified that can help predict more serious BSI. These results encourage the possibility of a more selective management strategy for these children.

Kamel, A., N. El-Sharkawy, D. Yassin, K. Shaaban, H.Hussein, I. Sidhom, S. Aboulnaga, M. Zamzam, O. El-Hattab, and A. N. H. El-Din, "P-gp expression and Rh 123 efflux assay have no impact on survival in Egyptian pediatric acute lymphoblastic leukemia patients", Journal of the Egyptian National Cancer Institute, vol. 17, pp. 165-172, 2005.