Frequency of Infectious Mortality at the End of Induction Chemotherapy in Acute Lymphoblastic Leukemia and Lymphoma Patients: Findings From a Tertiary Care Cancer Center.

Background and objective In low- and low-to-middle-income countries (LMICs), the incidence of treatment-related mortality (TRM) in patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) is up to 52%. This study aimed to determine the mortality rate at the end of the induction phase of the treatment among patients with ALL and lymphoma at a tertiary care cancer center. Methods This retrospective study analyzed outcomes after induction chemotherapy in pediatric patients with acute leukemia and lymphoma at a tertiary care cancer center from January 2015 to December 2016. Information regarding demographics, clinical characteristics, and laboratory investigations were extracted and reviewed. Results Of the total 160 patients, 110 were males, and the mean age of the sample was 4.6 +2.8 years. B-cell leukemia (pre-B-ALL) was diagnosed in 84% (n=134), while 10% (n=6) had acute T-cell leukemia (pre-T-ALL) and 6% (n=10) had lymphoma. Sixteen patients (10%) died within the defined induction period, with 14 deaths occurring due to infections and two deaths resulting from chemotherapy-related toxicity. Conclusion Based on our findings, there is a significant prospect of mortality from infections during induction chemotherapy in patients with pediatric hematological malignancies.

Orbital relapse in children treated for Pre-B ALL, a retrospective case series.

About 85-90% of children with B-cell leukaemia are cured. If relapse occurs it is usually in the bone marrow (BM), followed by extramedullary sites. Ocular lesions occur secondary to the accumulation of circulating blasts in the uvea, optic disc, intra-ocular tissue as well as fluid. Here we report four patients with ocular complaints that led to the diagnosis of relapse. Among 475 children with leukaemia treated from January 2013 to December 2018, 50 (10.5%) patients relapsed. Four (8%) out of these 50 presented with orbital symptoms. Central Nervous System (CNS) evaluation by cerebrospinal fluid (CSF) was negative at relapse. Relapse was treated with chemotherapy R3 protocol. Three (75%) patients are alive, while the fourth patient had a second BM relapse and died. Ophthalmic signs and symptoms in patients with treated leukaemia warrant a thorough evaluation. These signs can be an indication of relapse. BM and CSF studies should be done for diagnosing relapse.

Feasibility of Compressed Chemotherapy Pediatric Ewing Sarcoma Regimen In Pakistan.

A retrospective chart review was conducted to determine the feasibility of interval-compressed chemotherapy regimen in pediatric Ewing sarcoma (ES) patients treated at Department of Pediatric Oncology, Shaukat Khanum Memorial Trust Cancer Hospital, Lahore, Pakistan, from June 2017 to December 2018. Data was collected regarding demographics, treatment duration and timing, complications and outcome. Completion of treatment within 8 months as considered on time. There were 24 patients (male: female ratio = 1.4:1, average age = 10.2 ±5.3 years. Involved sites were extremity in 13 (54%), pelvis in 4 (16.6%), and spine in 3 (12.5%) patients. Twenty patients (83.3%) completed chemotherapy on time. The mean duration of treatment was 7.2 ±1.2 months. Only three patients (12%) exceeded 8 months of duration of treatment. There was an average of 2.5 febrile neutropenia events per patient. Seventeen (70.8%) patients are alive at the time of review. Two patients died of sepsis, one developed cardiac failure, and one died of progressive disease. This single-institution review showed that patients can tolerate interval-compressed chemotherapy protocol regimen for ES with adequate supportive care. Key Words: Ewing sarcoma, chemotherapy, Compressed regimen, feasibility, Pediatrics.

Outcomes of Advanced Retinoblastoma Treated with Local Salvage Treatment; a Retrospective Case Series.

Introduction: Retinoblastoma (RB) is the most common intraocular malignancy arising from the developing retina and occurs in approximately one of every 15,000-20,000 births. With the introduction of the intra-arterial chemotherapy (IAC), the 5-year overall survival of children with RB is 99%, though in low- and middle-income countries, it rarely exceeds 35% due to limited resources and lack of expertise. The aim of this study was to determine the outcome of local salvage in advanced RB. Materials and Methods: A retrospective analysis was conducted on children diagnosed with advanced RB that had local salvage therapy along with systemic chemotherapy from January 2015 to January 2018 at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Results: Fifteen patients were included in the study, among these 10 were male. The median age of presentation was 20 months (range 2-40 months). Among participants, 11 patients had bilateral RB. Fourteen patients received local control along with systemic chemotherapy. Relapse disease was seen in 12 patients and 2-year disease-free survival (DFS) was 20%. Conclusion: The results of the present study suggest that centres lacking the resources for IAC should treat advance cases of RB with an upfront or early enucleation.

Outcomes of Refractory and Relapsed Hodgkin Lymphoma With Autologous Stem-Cell Transplantation: A Single Institution Experience.

PURPOSE: Hodgkin lymphoma is the most common cancer in children, adolescents, and young adults. Overall survival is approximately 80% to 90%. A subset of these patients has refractory disease or experience disease relapse. Conventional salvage therapies and autologous stem-cell transplantation is usually considered the standard of care for these patients. Our analysis reports outcomes in these patients. PATIENTS AND METHODS: After institutional review board approval, a retrospective analysis of patients with Hodgkin lymphoma who were up to 18 years of age and who had refractory or relapsed disease at Shaukat Khanum Memorial Cancer Hospital and Research Centre from September 2009 to December 2013 was performed. Patients who underwent high-dose chemotherapy followed by stem-cell rescue were included in this analysis. RESULTS: A total of 567 patients with Hodgkin lymphoma registered at the hospital. Sixty of the patients (10.6%) had either primary progressive or refractory disease or relapse after finishing with first-line chemotherapy. High-dose chemotherapy followed by stem cell was administered to 25 of these patients (42%). Thirteen patients (40%) had progressive disease (PD), five (22%) had early relapse, and seven (38%) had late relapse. A number of salvage regimens were used, including etoposide, prednisolone, ifosfamide, and cisplatin; dexamethasone, cytarabine, and carboplatin; and gemcitabine plus vinorelbine. Re-evaluation was performed before taking patients to a high dose, and it showed complete response in 17 patients (68%), partial response in six patients (24%), and PD in two patients (8%). Twenty-one patients (84%) are in remission after transplantation, with two patients (8%) having died as a result of disease progression and two patients (2%) having relapsed after treatment. Overall survival is 92% at 4 years, with event-free survival of 80% at 4 years. CONCLUSION: Our retrospective analysis shows good outcomes in patients who had PD or refractory disease. Disease response before transplantation is important in predicting outcomes.

Pediatric Cancer Outcomes in an Intensive Care Unit in Pakistan.

PURPOSE: Although cancer is uncommon, it is a significant cause of pediatric morbidity and mortality in the developing world. The need for intensive care in pediatric oncology has increased with more intense chemotherapeutic interventions. It is important to identify patients who will benefit from management in the intensive care unit (ICU), given the resource limitation in developing countries. In this review, we examine our institutional experience with pediatric patients with cancer needing ICU care. METHODS: A retrospective chart review from December 2015 to June 2017 was performed with institutional review board approval for all pediatric oncology patients admitted to the ICU. Data collection included age, diagnosis, disease stage, Pediatric Risk of Mortality (PRISM III) score, and therapeutic interventions. RESULTS: We reviewed 59 pediatric oncology ICU medical records. There were 36 boys (61%) and 23 girls (39%). The median age was 4 years. Average stay in the ICU was 4.6 days. Three significant reasons for ICU referral were respiratory distress, sepsis, and circulatory collapse. There were 34 ICU survivors (57.6%). Among those who survived the ICU, 20 patients (58.8%) later died of therapy-related complications. Factors related to increased ICU mortality included the need for mechanical ventilation, the need for inotropic support, the number of failing organs, and a high PRISM III score. CONCLUSION: The mortality rate for pediatric oncology patients admitted to the ICU in developing countries is higher than in developed countries. Mortality was significantly related to the need for mechanical ventilation. PRISM III scoring can help identify patients who can benefit from ICU treatment, which is expensive in resource-limited low- and middle-income countries such as Pakistan.

I-131 mIBG Scintigraphy Curie Versus SIOPEN Scoring: Prognostic Value in Stage 4 Neuroblastoma

Objective: I-131 mIBG scan semi-quantitative analysis with modified Curie and the International Society of Pediatric Oncology Europe Neuroblastoma (SIOPEN) scoring systems is helpful in the evaluation of disease extent and has prognostic impact in stage 4 neuroblastoma. Methods: Retrospective, cross-sectional analysis of baseline I-131 mIBG scans in 21 patients with stage 4 or 4S neuroblastoma diagnosed between January 2007 and December 2015. All scans were assessed for Curie and SIOPEN scores. Distribution of scores was evaluated for risk factors i.e. age at diagnosis (>18 months) and early relapse (within 12 months). A curie score <2 and SIOPEN score <4 at diagnosis were correlated with event-free survival (EFS) and overall survival (OS). Results: The data set comprised of 12 (57%) males and 9 (43%) females. Patients with age >18 months (n=9) at diagnosis or early relapse (n=9) had higher Curie [mean 5+7.5 standard deviation (SD), p=0.004] and SIOPEN (mean 5.2+10.8 SD, p=0.02) scores. Patients with a Curie score <2 and a SIOPEN score of <4 had better EFS and OS than patients with higher scores. Curie: 5-year EFS=Curie <2 (79%) versus Curie >2 (33%) (p=0.03); 5-year OS=Curie <2 (56%) versus Curie >2 (36%) (p=0.01). SIOPEN: 5-year EFS=SIOPEN <4 (70%) versus SIOPEN >4 (17%) (p=0.002); 5-year OS=SIOPEN <4 (58%) versus SIOPEN >4 (17%) (p=0.04). There was no statistically significant difference between the two scoring systems in terms of survival predictive value (Hazard ratio 2.38, 95% CI: 0.33-16.9, p=0.38). Conclusion: I-131 mIBG Curie and SIOPEN scores have prognostication value in stage 4 neuroblastoma and should be routinely applied. Higher scores predict unfavorable prognosis.

Posterior Reversible Encephalopathy Syndrome in Pediatric Cancer: Clinical and Radiologic Findings.

PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is associated with a range of medical conditions and medications. In this retrospective analysis, we present 19 pediatric patients with PRES who had undergone chemotherapy. METHODS: We identified four female and 15 male patients diagnosed with PRES on the basis of clinical and radiologic features. Patient charts were reviewed from January 2013 to June 2016 after authorization from the institutional review board. RESULTS: The average age of patients with PRES was 7 years. Primary diagnoses were non-Hodgkin lymphoma (n = 9), acute pre-B-cell leukemia (n = 5), relapsed pre-B-cell leukemia (n = 2), Hodgkin lymphoma (n = 2), and Ewing sarcoma (n = 1). PRES occurred during induction chemotherapy in 12 patients. Sixteen patients had hypertension when they developed PRES. Most of these patients (n = 13) were receiving corticosteroids on diagnosis of PRES. Common clinical features were hypertension, seizures, and altered mental status. With the exclusion of three patients, all others required antiepileptic therapy. Ten of these patients underwent additional magnetic resonance imaging. Ten patients are still alive. CONCLUSION: In patients who presented to our center with signs and symptoms of hypertension, seizures, visual loss, or altered mental status, PRES was mostly seen in those who were undergoing systemic and intrathecal chemotherapy. Approximately 40% of the patients had reversal of clinical and radiologic findings. Antiepileptic medications were discontinued after being seizure free for approximately 6 months.

Radiotherapy Outcome for Pediatric Pelvic Ewing Sarcoma.

OBJECTIVE: To evaluate the outcomes of patients undergoing radiotherapy for primary local control of pelvic ewing sarcoma (ES). STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Shaukat Khanum Memorial Cancer Hospital, Lahore, from January 2010 to October 2015. METHODOLOGY: Patients with primary pelvic ES were included in the analysis and all other primary disease sites were excluded. All of them were treated with radiotherapy and followed the EuroEwing-99 chemotherapy protocol. Tumor volume, relapse and metastases were noted. RESULTS: There were 13 patients with pelvic ES. The median age at the time of diagnosis was 15 years with IQR of 7 years (range 2-19 years). Tumor volume was more than 400ml in more than 50% of the patients. Eight patients (61.5%) had local relapses and 5 patients (38.5%) had combined local and distant disease metastases. CONCLUSION: These results showed poor local control and overall survival in local pelvic ES cases in children and adolescents. Intensity modulated radiotherapy (IMRT) can be used to deliver higher doses of radiation. Compressed cycles of chemotherapy should be evaluated in local setting.

Bone Marrow Involvement in Metastatic Pediatric Ewing Sarcoma.

OBJECTIVE: To evaluate the frequency of bone marrow involvement with metastatic lung and bone sites in newly-diagnosed pediatric patients with Ewing sarcoma (ES). STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, from January 2010 to October 2015. METHODOLOGY: Newly-diagnosed pediatric-age patients with ES were inducted. Ten patients were excluded because bone marrow aspiration/biopsy (BMAB) was not done. Patients'medical records were reviewed for data collection of age, diagnosis, tumor volume, bone marrow diagnosis, metastatic work-up and outcomes. RESULTS: Atotal of 139 patients with median age of 12 years were identified. The median volume of tumors was 529 ml. Eleven patients had bone marrow (BM) disease involvement. Five (45.5%) had bone metastatic disease and 1 (9%) had both pulmonary and bone metastases. Four patients (31.1%) with positive BM had primary limb disease. CONCLUSION: Ewing sarcoma patients with bone metastatic disease have a higher frequency of BM involvement. However, BM can be involved without metastatic disease. BMAB should still be considered at staging for newly diagnosed pediatric patients with localized ES.