Cancer Hospital Egypt Research Articles

1088P - Impact of donor lymphocyte infusion in relapsing myeloid neoplasms post allogeneic hematopoietic stem cell transplantation

BackgroundDonor lymphocyte infusions (DLI) become one of the currently used approaches to treat post-transplant relapses. However, the wide use of the different DLI strategies, its effectivity and toxicity are still unpredictable in many patients. We evaluated the impact of DLI for patients with myeloid neoplasms experienced relapse post hematopoietic stem cell transplantation (HSCT). MethodsThis study included patients with myeloid neoplasms who received DLI post HSCT at the BMT unit, Children Cancer Hospital Egypt (CCHE-57357) from 2009 to 2017. DLI was given for patients with either rising minimal residual disease (MRD) or after systemic chemotherapy for those who experienced frank relapse. ResultsA total of 20 patients received post HSCT DLI were analyzed, with median age of 7 years. About 12 patients (60%) had acute myeloid leukemia (AML), 5 with chronic myeloid leukemia (CML) and 3 cases had myelodysplastic syndrome (MDS). Seven patients had frank relapse and given systemic chemotherapy followed by DLI upon complete remission, while 13 patients received only DLI due to rising MRD. Early relapse (during 1st year) was reported in 14 cases (70%) and 7 patients relapsed beyond 1st year post-transplant. Regarding the graft status at relapse, 15 patients had maintained complete chimera while 5 patients showed mixed chimera. The one-year disease free survival (DFS) and overall survival (OS) post DLI for the whole cohort were 54% and 64%, respectively with one patient had a non-relapse mortality and 6 patients developed graft versus host disease (GvHD) post DLI. According the initial diagnosis, DFS at one year was 80% for CML, 66% for MDS and 41% for AML patients. Also DFS was better for those with late relapse (70% vs 57% for early relapse) and for those who developed GvHD post DLI. ConclusionsDLI was associated with a durable efficacy and low toxicity in pediatric patients with hematologic malignancies. However, larger studies and standardized approaches are required to identify the outcome predictors of this treatment modality. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

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

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. A retrospective study included all patients with newly diagnosed ALCL from July 2007 till December 2015. 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. 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.

Castleman Disease Prevalence, Practice Essentials and Outcome Among Patients of the Children's Cancer Hospital–Egypt

Castleman Disease Prevalence, Practice Essentials and Outcome Among Patients of the Children's Cancer Hospital–Egypt

Overview and outcome of mucormycosis among children with cancer: Report from the Children's Cancer Hospital Egypt.

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Risk stratification of pediatric high-grade glioma: a newly proposed prognostic score.

High-grade glioma (HGG) is a clinical challenge. Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG-RPA) for HGG remains the standard for assessing the prognosis of adult HGG. This study assesses the validity of the RTOG-RPA to be applied to pediatric HGG. A retrospective study was conducted on 59 pediatric HGG treated in the Children's Cancer Hospital, Egypt (CCHE) between 2007 and 2016. Several factors were studied as predictors for the disease survival, including age, gender, increased intracranial hypertension, tumor characteristics and pathology, CSF seeding, performance status, post-surgical residual, and radiation dose. The statistically significant results were integrated into a Cox-regression model to develop a prognostic risk score. Kaplan-Meier statistics identified 13 factors that impacted the overall survival. However, Cox model showed that the histological grade IV [HR 14.2, 95%CI; (3.5-57), P < 0.0001], thalamic infiltration [HR 8.7; 95%CI; (2.9-25.9), P < 0.0001], PS ≥ 60 [HR 0.317; 95%CI; (0.13-0.776); P = 0.012], and maximum tumor dimension > 3.3cm [HR 10.2; 95%CI; (1.58-65.89); P = 0.015] were the independent variables that predicted the overall survival. A risk score was proposed based on the presence of one or more of these factors. The median OS for the low risk (score 0-1), the intermediate-low risk (score 2), the intermediate-high risk (score 3), and the high risk (score 4) were 40, 18.5, 9.5, and 2.5months, respectively, (P < 0.0001). The proposed model and risk score could stratify pediatric patients as the RTOG-RPA do for the adults.

PB2000 OUTCOME OF PEDIATRIC NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA, IS ABVD THE BEST REGIMEN? 10 YEARS SINGLE CENTER EXPERIENCE, REPORT FROM CHILDREN CANCER HOSPITAL, EGYPT.

Background:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma (HL) in children and accounts for 5–10% of all pediatric HL.Aims:The aim of the study to analyze the clinical characteristics and treatment outcome of Pediatric NLPHL.Methods:Retrospective study including all newly diagnosed patients less than 18 years old with NLPHL and treated in children cancer hospital Egypt CCHE between 2007 and 2017.Results:Among 43 pediatric NLPHL patients, 29 had early stage (18 with stage I, 11 with stage II). Fourteen patients had advanced stage (7 with stage III &amp; 7 with stage IV). Eleven patients had a mediastinal disease, 8 patients had splenic involvement, 2 patient had bulky disease and 10 patient had B symptoms at diagnosis.28 Patients with Early‐stage disease treatment; surgery and observation 6 patients, Chemotherapy 6 patients and Combined modality 17 patients. Relapse was seen in 7(25%) patients, 1 observation arm, 3 from chemotherapy arm (ABVD) and 3 from the combined arm (ABVD+IFRTH). 14 advanced stage patients received treatment; Chemotherapy (ABVD) 6 patients, Combined (ABVD+IFRTH) 8 patients, Relapse in 7 (50%) patients (all stage 4 disease), 6 from chemotherapy arm and 1 from the combined arm. 2 patients died (stage IV) from progressive disease and sepsis. B symptoms, mediastinal and splenic involvement had a significant impact on DFS on univariate analysis while combined treatment modality (Chemotherapy and Radiotherapy) had an impact on the outcome of both univariate and multivariate analysis.5 Years DFS, OS for whole group was 64% and 94% respectively, while 5y DFS for early stage 83% and advanced stage 45% (p‐value = .01) and 5 Years OS for early stage was 100% and advanced stage 87 % (p‐value = .08).Summary/Conclusion:Early stage NLPHL had a better outcome but unexpected higher relapse in chemotherapy treatment arm raising a question about the role of radiotherapy while advanced stage disease had poor outcome rising a question of what should be the best chemotherapy regimen for pediatric NLPHL patients.

PB1823 PROGNOSTIC FACTORS AND TREATMENT OUTCOME OF RELAPSING AND REFRACTORY MATURE B CELL NON HODGKIN LYMPHOMA CCHE EXPERIENCE

Background:Treatment of non‐Hodgkin lymphoma (NHL) is an example of successful therapy of cancer in children with a cure rate approximating 80%. Unfortunately, relapsed NHL has a dismal outcome, and customary treatment is by highly toxic chemotherapy followed by hematopoietic stem cell transplantation (HSCT).Aims:To analyze prognostic factors, and to report treatment outcome of relapsing/refractory mature B cell NHL.Methods:A retrospective analysis including all patients less than 18 years initially diagnosed as mature B cell NHL who were primary refractory to chemotherapy or relapsed during the period between July 2012 till end of 2017 at the Children Cancer Hospital Egypt (CCHE).Results:Out of 494 patients diagnosed during the study period, 34 (7%) were included in our study. Twenty‐three (67.6%) had Burrkitt lymphoma, while 5 (14.7%) had diffuse large B cell lymphoma. The majority were males (79.4%), with a median age 6.2 years. According to Modified Murphy Staging, 6 patients (17.6%) were stage II, 24 (70.6%) stage III, and 4 (11.8%) stage IV. Bone marrow (BM) involvement at presentation was detected in 2 patient, and 3 (8.8%) had CNS infiltration. Thirty patients (88.2%) received LMB protocol, and 4 (11.8%) R‐CHOP as primary chemotherapy. One patient (2.9%) was treated as low risk, 28 (82.4%) as intermediate, and 5 (14.7%) high risk. Median delay in 1st line treatment was 22 days (range 0 to 162).Twenty two patients (64.7%) relapsed, and 12 (35.3%) had tumor progression. Relapse was early in 15 (68.2%), and late in 7 patients (31.8%). It was documented by tissue biopsy in 30 patients (88.2%), and bone marrow aspirate in 3 (8.8%). Patients relapsed other than primary site were 6/34 (17.6%). CNS relapse was detected in 8 (23.5%), BM in 8 (20.5%), while combined BM and CNS in 2 (5.9%). R‐ICE was the 2nd line of treatment in 29 patients (85.3%), and complete 2nd remission (CR) was achieved in 7 patients (20.6%). Allogeneic HSCT was done for 2 patients (5.9%), and autologous HSCT for 3 patients (8.8%). Finally, 7/34 (20.5%) patients were alive in CR, and 24/37 (70.5%) died. The 3 years Overall survival (OS) 35.3%, with no statistical difference between relapsing and progression. The 3 years OS for patient who underwent HSCT was 80% compared 20% for no HSCT (p = 0.034).Summary/Conclusion:Our relapse rate is higher than the literature probably due to delay of chemotherapy with loss of dose intensity. For patients in second remission, HSCT markedly improves the outcome.

Management of pediatric CNS meningiomas: CCHE-57357 experience in 39 cases.

Our aim is to present our experience in the management of pediatric meningiomas in the largest referral center in Egypt for pediatric tumors focusing on variables including clinical picture, anatomic location, histopathology, treatment strategies, and outcome together with their possible correlation to prognosis. We retrospectively reviewed the medical records of 39 pediatric patients who were treated for CNS meningiomas in Children's Cancer Hospital-Egypt (CCHE-57357) 2007-2017. The prevalence of pediatric meningioma was 1.42%. Four cases had type 2 neurofibromatosis (NFII). The mean age was 8.19years. The presence of NFII was associated with challenging multiple lesions, older age of presentation and poorer prognosis and functional outcome. Convexity was the commonest location. Gross total resection (GTR) was achieved in 28 cases, subtotal resection (STR) in 8 cases, and biopsy was decided in 3 patients. Histopathological examination revealed WHO grade I in 16 patients and higher grades in 23 patients (59%). The 5-year overall survival (OS) rate was 87.8% while the 5-years event-free survival (EFS) rate was 85.6%. Tumor location, histopathology, and clinical presentation were not statistically correlated to prognosis. Pediatric CNS meningiomas are uncommon pediatric tumors but of an aggressive clinical and pathological behaviors as compared to adult meningiomas. The presence of NFII is associated with a poorer prognosis and functional outcomes. Although being challenging, the maximum and safe surgical excision should be exercised even in recurrent cases in order to achieve the best outcome. Adjuvant radiotherapy provides good tumor control for inoperable residual atypical or anaplastic meningiomas.

Survival and factors affecting the outcome of synovial sarcoma in children and adolescents single institute experience

Introduction: To check the impact of the clinical and pathologic features at diagnosis and treatment given, on the outcome of synovial sarcoma in children and adolescents.Methods: Retrospective analysis of patients below 18 years old diagnosed by synovial sarcoma and treated at Children CancerHospital Egypt 57,357 (CCHE) between July 2007 and December 2016. We reviewed Clinical characteristics, pathological information, treatment modalities and survival data.Results: We included thirty one patients with median age at diagnosis was 14.8 years. Initial surgical excision was possible in 10 patients (58.8%) while 5 (29.4%) patients underwent surgical excision after response to preoperative chemotherapy. Two patients had unresectable tumor, showed no response to chemotherapy and received radiotherapy as the only local control therapy. Adjuvant radiotherapy only was given in 2 patients and 5 patients received chemotherapy without local radiotherapy and 10 patients received both modalities. The estimated 5-year overall survival and failure free survival rates for the entire group were 84.4% ± 7.2% and 63.8% ± 9.7% respectively, the 5-year OS and FFS were studied in correlation to age of patient, tumor size, different pathological types, site of the lesion and methods of local control. In patients with tumor size below 5 cm when compared to size more than 5 cm with OS was (100%) in comparison to (79.3 ± 9.3) who underwent complete surgical excision either initial or post chemotherapy as it was 66.7% versus 55.6% for those with gross or microscopic residual (p-value = .38). Also, the 3-year failure free survival was 75% versus 56.3% for those smaller than or equal 5 cm and those larger than 5 cmrespectively (p-value = .3).Conclusion: Increasing number of patients to increase sample size to assess tumor size and complete surgical excision as important prognostic factors as in our study, we found them statistically insignificant. Preoperative chemotherapy can help for delayed excision in patients presented initially with unresectable tumors

Outcome and factors affecting survival of childhood myelodysplastic syndrome; single centre experience

Abstract Introduction Although many therapeutic options have been attempted for pediatric myelodysplastic syndrome (MDS), still hematopoietic stem cell transplant (HSCT) is the only curative therapy. We described the outcome of these patients and the factors affecting the overall survival (OS) and event free survival (EFS). Methods This is a retrospective descriptive study included 44 patients with MDS who presented to Children Cancer Hospital Egypt (CCHE-57357), between July 2007 and December 2015. HSCT was offered to patients who had HLA matched family donors. Results Eighteen patients (40.9%) had refractory cytopenia of childhood (RCC), 19 (43.2%) had refractory anemia with excess blasts (RAEB), and 7 (15.9%) had refractory anemia with excess blasts in transformation/myelodysplastic related acute myeloid leukemia (RAEB-T/MDR-AML). Cytogenetic abnormalities were observed in 54.8% of evaluable patients, in which monosomy 7 was the commonest abnormality observed (26.1%). Allogeneic HSCT from HLA matched donors was performed in 9/44 patients. The Average CD34 + count was 3.57 × 106/Kg recipient weight. The 2-year OS and EFS for the whole cohort were 43.3% and 33.8%, respectively, and for the transplanted patients were 75% and 60%, respectively. Univariate analysis showed improved 2 years-OS and EFS in patients who underwent HSCT as compared to those who didn't (75% versus 35.4% for OS, P = 0.088 and 60% versus 27.5%, for EFS, P = 0.074). Conclusion Allografts from either matched related or unrelated or even haplo-identical donors should be offered for pediatric MDS patients, as HSCT is the only curative option for those patients. Further collaborative efforts, a more precise molecular diagnosis, as well as large-scale prospective therapeutic trials are required to develop standard diagnostic and therapeutic guidelines for such rare disease.

Outcome and factors affecting survival of childhood myelodysplastic syndrome; single centre experience

IntroductionAlthough many therapeutic options have been attempted for pediatric myelodysplastic syndrome (MDS), still hematopoietic stem cell transplant (HSCT) is the only curative therapy. We described the outcome of these patients and the factors affecting the overall survival (OS) and event free survival (EFS). MethodsThis is a retrospective descriptive study included 44 patients with MDS who presented to Children Cancer Hospital Egypt (CCHE-57357), between July 2007 and December 2015. HSCT was offered to patients who had HLA matched family donors. ResultsEighteen patients (40.9%) had refractory cytopenia of childhood (RCC), 19 (43.2%) had refractory anemia with excess blasts (RAEB), and 7 (15.9%) had refractory anemia with excess blasts in transformation/myelodysplastic related acute myeloid leukemia (RAEB-T/MDR-AML). Cytogenetic abnormalities were observed in 54.8% of evaluable patients, in which monosomy 7 was the commonest abnormality observed (26.1%). Allogeneic HSCT from HLA matched donors was performed in 9/44 patients. The Average CD34 + count was 3.57 × 106/Kg recipient weight. The 2-year OS and EFS for the whole cohort were 43.3% and 33.8%, respectively, and for the transplanted patients were 75% and 60%, respectively. Univariate analysis showed improved 2 years-OS and EFS in patients who underwent HSCT as compared to those who didn't (75% versus 35.4% for OS, P = 0.088 and 60% versus 27.5%, for EFS, P = 0.074). ConclusionAllografts from either matched related or unrelated or even haplo-identical donors should be offered for pediatric MDS patients, as HSCT is the only curative option for those patients. Further collaborative efforts, a more precise molecular diagnosis, as well as large-scale prospective therapeutic trials are required to develop standard diagnostic and therapeutic guidelines for such rare disease.

Day +100 Platelet Count Predicts Survival After Allogeneic Hematopoietic Stem-Cell Transplantation in Children With Hematologic Malignancies

IntroductionRecovery of platelet count by day 100 after hematopoietic stem-cell transplantation (HSCT) is affected by many factors and has been reported to be a predictor of overall survival (OS) in a variety of diseases and donor types. We investigated the correlation between day +100 platelet count and OS after allogeneic HSCT in a relatively homogeneous cohort of pediatric patients with hematologic malignancies. Patients and MethodsWe conducted a retrospective study of 152 consecutive patients who underwent allogeneic HSCT at the Children’s Cancer Hospital Egypt between 2009 and 2015 with a minimum follow-up duration of 1 year after transplantation. All eligible patients received myeloablative conditioning, and all had matched related donors. Patients who survived without relapse until day 100 after HSCT were divided into 2 groups: early platelet recovery (EPR; platelet count ≥ 100 × 109/L at day +100 after transplantation) and delayed platelet recovery (DPR; platelet count < 100 × 109/L at day +100 after transplantation). ResultsAt day +100, 113 patients (74%) had EPR and 39 patients (26%) had DPR. With a median follow-up of 41 months (range, 12-93 months), 41 patients (27.2%) died, 35 of relapsed disease. The 3-year disease-free survival (DFS) and OS were 68 ± 7.84% and 71.9 ± 7.84%, respectively. The 3-year OS was 77.9% in the EPR group and 57.1% in the DPR group (P = .006). Three-year DFS of the EPR and DPR groups were 73.2 ± 9% and 54.8 ± 16.3%, respectively (P = .02). Incidence of disease relapse for EPR and DPR patients was 22.6% and 39.5%, respectively (P = .04). Multivariate analysis for survival identified DPR as a predictor of decreased survival (P = .002). ConclusionPatients with a robust platelet count at day 100 are likely to do well. However, patients who do not experience a platelet count of ≥ 100 × 109/L have inferior long-term OS and DFS and may require further evaluation at the day 100 time point.

Surgical Role in Management of Intracranial Germ Cell Tumors in Pediatric Age Group

Introduction: Primary intracranial germ cell tumors (ICGCTs) are rare, histologically diverse, and diagnostically challenging tumors that are usually localized in the pineal and suprasellar regions of the brain. Advanced neurosurgical techniques such as neuroendoscopy and frameless stereotactic biopsy have made diagnosis of newly discovered cases of ICGCTs easier and safer. Material and methods: Seventeen patients with intracranial germ cell tumors operated upon between 2008 to 2012 at the Children's Cancer Hospital Egypt, were retrospectively reviewed and analyzed regarding the surgical decision, clinical outcome and surgical complications. Results: There were 9 cases of germinoma (53%), and 8 cases of non-germinomatous germ cell tumors (47%). Nine cases were in the pineal region, six in the suprasellar, and two in the thalamic region. Ten cases were operated upon initially by open surgery and frozen section with subtotal resection and seven cases were biopsied either endoscopically (3 cases) or by frameless guided stereotaxic (4 cases). Accurate pathology was achieved in all biopsied cases without major complications. In the germinoma group, the 4-year overall survival and progression free survival rate were 75% for both at a median follow up period of 26 (range 1 -50) months. For the non-germinomatous germ cell tumors group, the 4-year OS and PFS rates were 36.5% and 31.2% at a median follow up period of 11 (range 2-54) months, respectively. Conclusion: In cases of intracranial germ cell tumors with negative tumor markers the role of surgery is important in the establishment of proper histopathological diagnosis. However, in Non Germinomatous Germ Cell Tumors, further investigations should be done regarding the extent of resection owing to the poor long-term outcome.

The Impact of Pretransplant Disease Characteristics on the Outcome of Autologous Stem Cell Transplantation for Neuroblastoma with High-Risk Features: A Retrospective Model from a Limited Resources Country

High-risk neuroblastoma still has poor survival outcome. Improvement of outcome is attributed to the consolidation of chemotherapy by autologous bone marrow transplant. Further improvement of the outcome by tandem autologous transplant is followed by immune therapy. We aimed with this study to correlate initial disease characteristics with the outcome of transplanted high-risk neuroblastoma. A retrospective analysis was done for 73 transplanted patients. Patients were treated in Children’s Cancer Hospital Egypt from July 2012 to July 2015. Seventy patients received Busulphan/Melphalan conditioning. The 3-year overall survival (OS) and event-free survival (EFS) was 63.3% and 51.3%, respectively. Disease stage did not impact the OS and EFS, P = 0.54 and 0.62 respectively. Status of MYCN did not reflect statistically on outcome for tumors with amplified compared to nonamplified (EFS, 49% and 63.1%, respectively). Response after induction chemotherapy pointed that patients who had objective response (complete response, very good partial response and partial response) were better compared to those with less response with EFS and OS of 53.3% and 64.2% compared to 49.3% and 63.5%, respectively, which may indicate that chemo-sensitive tumors have better outcome. By the end of the study, twenty-seven patients relapsed, out of them 25 patients died. Pretransplant risk features for neuroblastoma was nullified by autologous stem cell transplant. The modest outcome observed, highlights some limitations that need to be sorted out in countries with limited resources. The introduction of immune therapy and tandem transplant is needed to achieve a better outcome, yet it adds to more financial burden.

Outcome of Childhood Acute Megakaryoblastic Leukemia: Children’s Cancer Hospital Egypt 57357 Experience

IntroductionAcute megakaryoblastic leukemia is a rare subtype of pediatric acute myeloid leukemia (AML) with poor outcomes in patients with non–Down syndrome. The reported outcomes have been poor, and the prognostic factors have not been clearly determined. Patients and MethodsTo evaluate the prognostic significance of various cytogenetic abnormalities and minimal residual disease status determined by flow cytometry after induction I, we retrospectively analyzed the data of 80 patients with non–Down syndrome with a diagnosis of M7 AML treated at Children’s Cancer Hospital Egypt (CCHE-57357) from July 2007 through December 2016. ResultsOf the 80 patients, 15 died during induction I and were excluded from the survival analysis. The overall survival, event-free survival, and cumulative incidence of relapse at 2 years was 52.6% ± 12.7%, 45.2% ± 12.3%, and 31.8% ± 11.5% respectively. Of the 90 patients, 61 had cytogenetic abnormalities, including trisomy 19,13q, trisomy 8, complex karyotype, t(1;22), KMT2A rearrangements, and trisomy 21. None of these had an effect on the outcomes. In addition, 34 patients had minimal residual disease < 0.1% after induction I, but the difference did not reach statistical significance. Patients with a delayed time to recovery (possibly due to myelofibrosis) had worse outcomes compared with those with early recovery (47% ± 19.2% vs. 63.2% ± 21.9%, respectively). ConclusionAcute megakaryoblastic leukemia in patients with non–Down syndrome has a poor outcome with no clearly defined prognostic factors. However, future directions to risk stratify and tailor therapy should include assessment of the tumor biology according to the molecular pathways and study of the pathogenesis of myelofibrosis in this disease, which could affect the prognosis.

Enhancing a Specialized Nursing Care Guidelines Improves Acute Lymphoblastic Leukemia Patients' Outcome during Induction Phase; A Developing Country Experience

Introduction: Pediatric Cancer patients are treated with therapeutic research protocols that detail medical treatment in low- and middle-income countries (LMICs). Unfortunately, there is no precise definition of a structured nursing care plan that is mandatory to enhance the quality of care needed for these patients. Our study aimed to examine the impact of implementing a designed nursing care guidelines (NCG) on acute lymphoblastic leukemia (ALL) patient outcomes during the induction phase concerning; incidence, duration, and intensity of the patient's gastrointestinal tract GIT adverse events.Methods: A Quasi-experimental research design was utilized in this study with posttest only control group conducted at the Hematology Units of Children Cancer Hospital Egypt 57357. Seventy-four oncology nurses received adequate education for the designed nursing care plan. A total of (132) ALL children in induction phase were enrolled in the study and were divided into two groups: group 1 (intervention group) was implemented the nursing care guidelines and group II (control group) who was left to the routine hospital care.Tools: data collection instruments included; “patient outcomes audit chart” to assess the GIT adverse - events data: the incidence, duration, and intensity. The intensity grading of the adverse events Adopted from the NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events v4.0 (CTCAE) Published on May 28, 2009.Results: A significant positive correlation between implementing the NCG and GIT adverse events incidence, duration and severity were observed (Figure 1). Incidence was reported higher in the control group than the study group with a mean score of ±SD (2.48± .949) versus (0.67± 0.751) respectively, and a p-value (P<0.0001). The duration of incidence was (15.32± 5.920) versus (3.70± 5.108) in the intervention group (t =12.074) df (130) and a p-value (P<0.0001). The intensity grading of the adverse events was less in the study group than the control. (figure 2)Mean scores for nurses' post-NCG knowledge in the study group were significantly higher than the nurse's knowledge scores in the control group. The intensity of incidence revealed that a significantly higher on the intervention group.Conclusion: Designing and implementing NCG for all treatment protocols is essential for the enhancement of patients' outcomes. Developing a pediatric oncology nurse residency program for education and teaching of the required practical skills in LMIC is mandatory.Figure 1 Figure 2 DisclosuresNo relevant conflicts of interest to declare.

2437. Colistin Usage, Do We Need to Worry About Its Toxicity Among Children With Cancer?

BackgroundGram-negative bacteria susceptible only to colistin are emerging causes of complicated infections especially in the immunocompromised patients, reviving interest in the use of colistin. The purpose of this study was to test the renal toxicity along with efficacy of a salvage therapy with a colistin among pediatric cancer patients in our hospital.MethodsA prospective, observational, cohort study was performed from May 2017 to October 2017 in Children’s cancer hospital Egypt 57357. All patients who had Blood Stream Infections due to COS Gram-negative bacteria and received intravenous Colistin were prospectively enrolled. A standardized case form was used to record patient characteristics, including age, sex, weight, underlying comorbidities, type of infection, causative organism and in vitro susceptibility, daily doses and duration of colistin therapy, cumulative dose of colistin, co-administered antibiotics, nephrotoxic agents, and clinical and microbiological responses to therapy, daily serum creatinine clearance, and estimated creatinine clearance were recorded.ResultsOne hundred and Thirty-four Blood Stream infectious episodes due to Klebsiella species (pneumoniae and Oxytoca) (32%), and E. coli (68%) were analyzed. All strains were fully susceptible to colistin, with MICs of 0.19–1.5 mg/L. It was employed as combination therapy with carbapenems (69.2%) or aminoglycosides (30.8%). Median duration of treatment was 9 days (range 1–50 days). Clinical and Microbiological cure was observed in 107 cases (80%). Acute kidney injury developed during 5 treatment courses (4%)in combination with Amikacin. No renal replacement therapy was required and subsided within 7 days from Colistin discontinuation. No correlation was found between variation in serum creatinine level (from base line to peak) and daily and cumulative doses of CMS.ConclusionOur study shows that in severe infections due to COS Gram-negative bacteria, Colistin had a high efficacy, without significant renal toxicity. Looking into the failure of microbiological cure, we need to further study the possibility of increasing the Colistin with cautious monitoring of renal functions, and Therapeutic Drug monitoring. Furthermore, the bacterial isolates should be studied at the genetic level for resistance.Disclosures All authors: No reported disclosures.

A Pharmacogenetic Study of VDR fok1 and TYMS Polymorphisms and Their Association With Glucocorticoid-Induced Osteonecrosis in Egyptian Children With Acute Lymphoblastic Leukemia.

Purpose: 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.Patients and Methods: 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.Results: 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; P-values 0.3808 and 0.1503, respectively, nor with ALL subtypes; P-values 0.9396 and 0.6596, respectively. The VDR fok1 polymorphisms showed a significant association with the development of ON; P-value = 0.003, on the other hand, TYMS tandem repeats did not show significant impact on osteonecrosis development; P-value = 0.411.Conclusion: 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.

Osteonecrosis in children with acute lymphoblastic leukemia: A report from Children's Cancer Hospital Egypt (CCHE)

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. 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. 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 796mg/m2 , and the mean total corticosteroid dose, calculated as prednisolone equivalence, was 6,431mg/m2 . Out of 43 patients who developed ON while on corticosteroid therapy, 36 (84%) required dexamethasone dose modification and/or discontinuation. 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.

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt

AimThe 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. MethodsThe 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). ResultsThe 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). ConclusionA 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.