Superior mediastinal syndrome in paediatric B-cell acute lymphoblastic leukaemia: a case report.

Superior mediastinal syndrome secondary to an anterior mediastinal mass can be seen in acute lymphoblastic leukaemia (ALL) of T-cell lineage. We report a 3-year-old child with B-cell ALL, who presented with the superior mediastinal syndrome. The CT scan chest showed a huge anterior mediastinal mass and the peripheral blood immunophenotyping showed B-cell ALL. High-risk remission induction chemotherapy was given and he achieved remission by the end of induction therapy, both in terms of medullary and extramedullary disease, and is on maintenance chemotherapy now. This is the first reported case of a paediatric B-cell ALL presenting with superior mediastinal syndrome secondary to an anterior mediastinal mass.

Acute leukaemia in children with Down syndrome in a low middle-income country.

Down syndrome (DS) is the commonest chromosomal disorder and is considered to be the most common syndrome associated with acute leukaemia. The objective of this study was to determine the characteristics of acute leukaemia in children with DS in Pakistan. It was a retrospective, cohort study conducted over a 2-year period, and the data was analysed in SPSS 20.0 in terms of descriptive statistics. Nineteen DS patients with acute leukaemia were enrolled. The proportion of DS-acute leukaemia was found to be 1.84% among all cases of paediatric acute leukaemia. The mean age of presentation was 5.5 years ± 4.3 SD with a male to female ratio of 1.1:1. The precursor B-cell ALL was found in 13 (68.4%) and acute myeloid leukaemia was found in 6 (31.6%) patients of DS. Thirteen patients (68.4%) completed treatment, while 6 (31.6%) expired due to treatment-related toxicity. Mean overall survival was 38 months ± 5.34 SD. The status of diagnosis of DS before presentation with acute leukaemia was the only statistically significant factor associated with the outcome. Few distinct characteristics of DS-acute leukaemia have been found in our population. Treatment toxicity was the sole cause of treatment failure.

T lymphoblastic lymphoma with BCR-ABL negative chronic myeloid leukaemia: a novel association.

Lymphoblastic lymphoma and chronic myeloid leukaemia (CML) are two distinct neoplasms with different pathogenesis and clinical presentation. We hereby share a challenging case of a child presenting with fever, leucocytosis, generalised lymphadenopathy and massive splenomegaly. He was diagnosed as having novel association of concurrent T-lymphoblastic lymphoma diagnosed on cervical lymph node biopsy with BCR-ABL negative CML on bone marrow aspirate. The study of more such cases is needed for optimal patient management.

Treatment-related mortality in children with acute lymphoblastic leukaemia in a low-middle income country.

OBJECTIVE: To determine the proportion of treatment-related mortality among mortalities of paediatric acute lymphoblastic leukaemia and to identify probable causes and risk factors. METHODS: The observational retrospective study was conducted in February-March 2019 at the Department of Paediatric Haematology-Oncology and Bone Marrow Transplant, the Children's Hospital and the Institute of Child Health, Lahore, Pakistan, and comprised data of all paediatric patients of acute lymphoblastic leukaemia who expired during treatment from January 2017 till September 2018. Death due to relapse and deaths before treatment were excluded. Data was analysed using SPSS 16. RESULTS: Of the 247 deaths during the study period, 144(58.3%) were treatment-related mortality cases; 81(56.2%) males and 63(43.8%) females with an overall mean age of 5.0±3.83 years. The commonest cause was sepsis 126(87.5%), followed by haemorrhagic complications 11(7.6%), drug toxicity 4(2.8%), tumour lysis syndrome 2(1.4%) and thromboembolism 1(0.7%). Significant factors associated with treatment-related mortality were weight-for-age, immunophenotype, the reason for admission, and absolute neutrophil count (p<0.05). CONCLUSIONS: Treatment-related mortality, though potentially avoidable, was found to be a major cause of death among paediatric patients of acute lymphoblastic leukaemia, and sepsis was the most common cause.

Infection Prevention and Control Measures at the Children Hospital Lahore: A My Child Matters Collaborative Project.

PURPOSE: Infection prevention among children with cancer is a major challenge at Children Hospital Lahore (CHL), a public health care facility in Pakistan with 1,000 new pediatric cancer admissions annually. The objective has been to reduce infections through collaboration between CHL and the St Jude Children's Hospital Global Infectious Disease program via a grant by the Sanofi Espoir foundation through the My Child Matters program. The aim of the current study was to describe the effect of the collaborative improvement strategy on existing infection prevention and control (IPC) standards at CHL. MATERIALS AND METHODS: Our work was a prospective before-and-after study to improve IPC standards. We compared the WHO Hand Hygiene Self-Assessment Framework and four modules of the St Jude modified Infection Control Assessment Tool (ICAT) scores over a 3-year period. Our strategy included creating a multidisciplinary team of pediatric oncologists, infectious disease physicians, nurses, a microbiologist, and a data manager; engaging in monthly online IPC mentoring sessions with St Jude Children's Hospital Global Infectious Disease program and My Child Matters mentors; performing daily inpatient health care-associated infection surveillance rounds; and performing regular hand hygiene training and compliance audits. RESULTS: Baseline needs assessment showed health care-associated infections identified by positive blood cultures as 8.7 infections per 1,000 patient-days. Deficient hand hygiene supplies, health education measures, and bed sharing of neutropenic patients were identified as major challenges. Our hand hygiene facility level, per WHO scores, increased from Inadequate to Intermediate/Consolidation by the end of the 3-year implementation (122 v 352 WHO Hand Hygiene Self-Assessment Framework scores). The sink:bed and hand sanitizer:bed ratios improved to 1:6 and 1:1, respectively. The ICAT general infection control module increased by 40% (45 v 78 ICAT scores) and hygiene compliance improved by 20%. CONCLUSION: Implementing a collaborative improvement strategy improved IPC standards in our center, which can be easily replicated in other pediatric oncology centers in lower- and middle-income countries.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.

Induction-remission response in peadiatric acute lymphoblastic leukaemia, Lahore protocol versus UKALL 2011 interim guidelines.

OBJECTIVE: To compare the outcome of induction-remission in acute lymphoblastic leukaemia patients treated according to two different guidelines. METHODS: The descriptive retrospective cohort study was conducted at The Children's Hospital Lahore, Pakistan, and comprised clinical information sheets of acute lymphoblastic leukaemia patients from September 2014 to August 2015. Data regarding demographics, risk categorisation, rapid early response and induction-remission assessment was collected separately for Group 1 patients treated with Lahore protocol and Group 2 patients using United Kingdom acute lymphoblastic leukaemia-2011 interim guidelines. Data was analysed using SPSS version 20.0. RESULTS: Of the 98 patients who had a median age of 6.4 years (interquartile range: 1.5-16 years), 48(49%) were in Group 1 and 50(51%) in Group 2. There were 14(29%) patients with standard risk in Group 1 while 34(71%) were high-risk. The corresponding numbers in Group 2 were 30(60%) and 20(40%) in Group 2. Rapid early response was noted in 18(37.5%) patients in Group 1 and 11(28%) in Group 2. Remission was achieved in 38(79%) patients in Group 1 and 36(72%) in Group 2. There was significant association of rapid early response with induction-remission in Group 2 (p<0.05) but not in Group 1 (p>0.05). CONCLUSIONS: Induction-remission rate was comparable in the two treatment groups, but significant association of rapid early response with induction-remission was observed only in patients treated using United Kingdom acute lymphoblastic leukaemia-2011 interim guidelines.

Pediatric Malignant Mediastinal Masses.

OBJECTIVE: To describe the clinical spectrum and outcome-associated variables of pediatric malignant mediastinal masses in a resource-limited setting. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Pediatric Hematology-Oncology, The Children's Hospital, Lahore, from October 2016 to November 2017. METHODOLOGY: Children with malignant mediastinal masses were enrolled. The variables studied were median age at presentation, gender distribution, immunisation status, socio-economic background, causes of delayed presentation, presenting complaints, complications of disease, methods for mass biopsy, final diagnosis, staging, and outcome of the disease. Results were described in terms of descriptive statistics. RESULTS: The median age at diagnosis was 7.5 years with male-to-female ratio of 2:1. The commonest presenting complaint was fever (82%), respiratory distress (58%), and lymphadenopathy (51%). Seventy-eight percent patients belonged to lower socio-economic class. Eighty-six percent of patients had delayed presentation to the tertiary care hospital and the most common reason was delayed diagnosis by the medical professionals (49%). Fifty-one percent patients had weight-for-age less than 5th percentile. Common complications were airway obstruction (35%), pericardial effusion (19.6%), superior vena cava syndrome and gross pleural effusion (13.7% each). Commonest diagnosis was T-cell acute lymphoblastic leukemia (35%) followed by lymphoblastic lymphoma and Hodgkin's lymphoma (15.7% each). Fourtyfive percent patients expired, 2% defaulted treatment and 5.9% completed treatment; 25% patients were under treatment, 3.9% patients had progressive disease while outcome of 17.6% of patients could not be known. The most significant factor associated with the outcome primary diagnosis (p<0.001), delayed presentation (p=0.007) and educational status of the family. CONCLUSION: The pattern of clinical presentation, complications and diagnoses of pediatric malignant mediastinal masses showed some variation from the already reported. Low literacy rate and delay in presentation are common and contribute significantly to the poor outcome.

Polymorphism of Interleukin-10 (IL-10, -1082 G/A) and Interleukin-28B (IL-28B, C/T) In Pediatric Acute Lymphoblastic Leukemia (ALL).

We conducted genotypic analyses of interleukin-10 (IL-10) (-1082 G/A; GG, GA, AA) and interleukin-28B (CC, CT, TT) genes polymorphisms in acute lymphoblastic leukemia (ALL) pediatric patients in descriptive study to evaluate the prevalence of these mutations. In amplification refractory mutation system-PCR (ARMS-PCR), one reaction was carried out for each patient's DNA sample. For IL-28B gene, two forward and two reverse primers specific for C-allele and T-allele were used separately. For human IL-10 gene, two different forward primers specific for A and G alleles were used in combination with common reverse primer. IL-10 gene promoter showed highest frequency (n=29, 58%) of heterozygous (GA) allele, while genotypic analysis of IL-28B gene showed highest frequency (n=28, 56%) of homozygous (CC) allele. The IL-10 (AA) genotype related to its protein's less production in body which may be associated with the least survival of ALL's patients, while IL-28b (CT and TT) genotypes may be associated with less IFNλ3 levels and less life expectancy.

Clinical features and outcome in paediatric newly diagnosed immune thrombocytopenic purpura in a tertiary care centre.

OBJECTIVE: The study aimed to demonstrate the pattern of clinical presentations and outcome of acute Immune Thrombocytopenia (ITP) in our Centre. METHODS: A descriptive, observational study was conducted by collecting and analysing the data of 103 patients of acute ITP, ageing between 1-14 years, at The Children's Hospital, Lahore from January 2016 to December 2016. We collected the data regarding age, sex, clinical presentations, history of preceding viral infections, vaccination history, laboratory values, different treatment options used, and response to the treatment concerning complete response, partial response and poor responders. Statistical analysis performed by using IBM SPSS statistics version 20. RESULTS: We retrospectively, reviewed total 103 patients cases. The median age, at the time of presentation, was 5±3.4 years while mean age was 4.5±2.9 years. The male to female ratio was 1.28:1. Mean platelet count on presentation was 7 x 109/L (range: 0-24). Twenty three (22.3%), patients had the history of preceding illness. Bruises, petechiae, epistaxis and hematemesis remained the common presentations. Six (5.8%) patients showed spontaneous recovery while 97 (94%) patients received treatment for ITP. Overall, 71 (68.9%) showed a response after treatment. Sixty-two patients (59.22%) showed loss of response and received treatment again. Among these patients, thirty-four patients (33%) developed chronic disease. CONCLUSION: Majority of patients presenting to our tertiary care centre had severe acute ITP on presentation. After management and follow-up, almost 1/3 of the patients develop chronic disease hence the incidence of developing chronic disease remained high as compared to the other centers.

Demographics and Outome in Paediatric Non-Hodgkin Lymphoma: Single Centre Experience at The Children Hospital Lahore, Pakistan.

OBJECTIVE: To describe the patient demographics and outcome analysis in paediatric non-Hodgkin lymphoma (NHL) patients. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: The Hematology/Oncology Unit of The Children's Hospital and Institute of Child Health, Lahore, from January 2012 till December 2014. METHODOLOGY: Demographics including age, gender, histopathology, stage and outcome data, in biopsy proven NHL patients were analyzed. Burkitts/B Cell and Diffuse Large B Cell lymphoma patients were treated with MCP 842 Protocol while T/B-cell lymphoblastic lymphoma (LL) patients were treated with EURO-LB 02 protocol. RESULTS: Ninety-one patients were treated during the study period at CHL. Data was insufficient in 18 patients, so they were excluded from the study. Patients included were 73. Males were 53 (72.6%). Thirty-seven (50.7%) were 5-10 years of age, and 22 (30.1%) 10-16 years old. Abdominal mass was the commonest presentation seen in 32 (43.8%), lymphadenopathy in 27 (37%), intussusception in 5 (6.8%), while intestinal obstruction, obstructive uropathy, nasopharyngeal mass, gastric mass, primary bone lymphoma, pericardial effusion, jaw swelling, cheek swelling and paraspinal mass present in one (1%) each. Histopathological subtypes consist of Burkitt's lymphoma (BL) in 32 (43.8%), B cell NHL in 10 (13.7%), lymphoblastic lymphoma (LL) in 26 (35.6%), diffuse large B cell lymphoma (DLBCL) in 2 (2.8%), and anaplastic large cell lymphoma (ALCL) in 1 (1.4%). Sixty-seven (91%) presented in stage III, and six (8.4%) in stage IV. Forty-eight (65.8%) patients had completed treatment and are well to date, 16 (21.9%) died, 5 (6.8%) left against medical advice (LAMA), and 4 (5.5%) patients relapsed. CONCLUSION: Burkitts lymphoma was the commonest type of NHL seen in this cohort that predominantly presented with an abdominal mass. Children usually presented in advanced stage with delayed diagnosis. Better supportive care can improve the prognosis significantly. Training of pediatricians is equally important along with increasing parental/family knowledge about the disease symptoms so that they can seek early medical care, and earlier diagnosis is possible.

Familial Hodgkin Lymphoma.

Hodgkin Lymphoma (HL) is a lymphoid tumour that represents about 1% of all neoplasms occurring worldwide. HLis the most treatable of childhood malignancies. The etiology of HLis unknown. However, increase risk has been reported in males, with autoimmune diseases, poor socioeconomic status, increased family size, Ebstein Barr Virus (EBV) exposure, congenital or acquired immunodeficiency and those with a family history of HL. Familial HLis rare. The risk of developing HLis increased six times in the siblings of the affected patients. Both genetic and environmental factors have been postulated in the pathogenesis. No case of familial HLhas been reported in the literature from Pakistan. We report two families with familial HLoccurring in siblings that have been successfully treated and are on our follow-up.

Paraneoplastic Cushing Syndrome Due To Wilm's Tumor.

Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to neoplasm. Paraneoplastic syndromes may be the first or the most prominent manifestations of cancer. Wilm's tumor is the most frequent pediatric renal malignancy and usually presents with abdominal mass. Unusual presentations like acquired von Willebrand disease, sudden death due to pulmonary embolism and Cushing syndrome have been described in the literature. Cushing syndrome, as the presenting symptom of a malignant renal tumor in children, is a very rare entity. Few case reports are available in the literature exploring the option of preoperative chemotherapy as well as upfront nephrectomy. We report a rare case of paraneoplastic Cushing syndrome due to a Wilm's tumor. Based on gradual decrease of postoperative weight, blood pressure, serum adrenocorticotropic hormone, and plasma cortisol levels, along with histological confirmation of Wilm's tumor, paraneoplastic Cushing syndrome due to Wilm's tumor was confirmed.

Comparison of Presentation and Outcome in 100 Pediatric Hodgkin Lymphoma Patients Treated at Children Hospital, Lahore, Pakistan and Royal Marsden Hospital, UK.

OBJECTIVE: To compare differences in demographics and outcomes in childhood Hodgkin lymphoma (HL) presenting at the Children's Hospital Lahore (CHL), and Royal Marsden Hospital (RMH), UK. STUDY DESIGN: An observational comparative study. PLACE AND DURATION OF STUDY: From January 2011 to February 2012 at CH, Lahore and from October 2008 to February 2012 at RMH, UK. METHODOLOGY: Consecutive HL patients (50 from each hospital) were inducted. Data regarding age, gender, staging, histopathology and outcome were analysed. Clinical and pathological staging done according to Ann-Arbor and World Health Organization classification. Treatment duration was 6-8 months. They were followed for 6 months post-treatment. Frequencies of variables were noted and compared. Chi-square test was used for determining significance. RESULTS: Patients from Children's Hospital, Lahore were younger (mean 7.9 years) with male predominance (n=42, 84%). Histopathology showed Mixed Cellularity (MC) in 32 (64%), Nodular Sclerosis (NS) in 5 (10%), Lymphocyte Rich in 4 (8%) and lymphocyte depleted in 1 (2%), nodular lymphocyte predominant (NLP) in 1 (2%) each. Majority presented in stage IV (n=25,50%), or stage III (n=20,40%). Constitutional B symptoms were present in 37 (74%). Bone marrow involvement observed in 23 (46%). Remission was achieved in 42 (84%) patients; 2 (4%) relapsed, 4 (8%) expired and 2 (4%) left against medical advice. In contrast, RMH patients were older (mean 11.8 years.) and 30 (60%) were males. NS (n=40,80%) and NLP (n=6,12%) types were predominant. Two (4%) patients were in stage I, 27 (54%) in stage II, 12 (24%) in stage III and 9 (18%) presented in stage IV. Fourteen (28%) had B-symptoms. None had bone marrow disease. Event free survival was 46 (92%). Four (8%) patients relapsed. Three responded to second line therapy and one relapsed postautologous transplant. CONCLUSION: Significant differences were observed in age at presentation, stage, histopathology and extent of bone marrow involvement between the groups. Of interest is the bone marrow involvement in stage IV patients in Pakistan. Delayed diagnosis account for advanced stage but difference in pathological subtype needs further study.

Ollier's Disease with Myelodysplastic Syndrome.

Ollier's disease also known as enchondromatosis is a rare skeletal disorder that is usually sporadic, non-hereditary, and characterized by abnormal bone development (skeletal dysplasia). While this disorder may be present at birth (congenital); it may not become apparent until early childhood with more obvious symptoms, such as deformities or improper limb growth. It carries high risk of skeletal, visceral and brain malignancy seen in approximately 25% of patients. Occurrence of Ollier's disease with myelodysplastic syndrome has never been reported in the literature. The different types of myelodysplastic syndromes are diagnosed based on certain changes in the blood cells and bone marrow characterized by one or more cytopenias despite a relatively hypercellular bone marrow. We hereby report the case of a 14 years boy who presented with painless finger swelling and hepatosplenomegaly. Radiological and bone marrow findings confirmed the diagnosis of Ollier's disease with Refractory Anemia and Excess Blasts (RAEB-1).

Intrarenal neuroblastoma: a diagnostic challenge.

Abdominal masses in children are usually retroperitoneal in location and 50% are renal in origin. In infants less than 2 months, majority of renal masses are benign; frequency of malignancy increases with age. Wilms'tumor is the commonest solid intrarenal tumors. However, occasionally neuroblastoma occurs in the kidney. Neuroblastoma in 50% of cases presents before 2 years of age, and 75% before 4 years. Neuroblastomas can occur anywhere along the neuroectodermal sympathetic chain, although adrenal medulla is the commonest site (50 - 70%). Intrarenal neuroblastoma is a rare clinical diagnosis. It clinically and radiologically mimics Wilms'tumor and it is difficult to differentiate between the two preoperatively. Lung metastasis and vascular invasion are also rare in neuroblastoma but rather common in Wilms'tumor. We present case of a patient who had extensive renal involvement with neuroblastoma and pulmonary metastasis, clinically and radiologically it was difficult to differentiate between the Wilms'tumor and neuroblastoma.

Primary renal Ewing's sarcoma: a rare entity.

Ewing's sarcoma, a primitive neuroectodermal tumour is a rare entity belonging to a family of neoplasms of neuroectodermal origin. These highly aggressive neoplasms primarily affect older children and young adults. They primarily involve the bones or soft tissues. A quarter of Ewing's sarcomas occur principally in the soft tissues with primary involvement of the kidney being exceptionally rare. We hereby, present a case of 6 years old girl child with primary Ewing's sarcoma of the kidney who presented with abdominal mass and posed much diagnostic challenge. The patient underwent complete surgical excision of tumour, and is being treated with aggressive adjuvant chemotherapy.