Childhood acute iymphoblastic leukaemia: Experience from a single tertiary care facility of Pakistan

Objective: To evaluate the demographic features, outcome and prognostic factors seen in children with acute lymphoplastic leukaemia at a tertiary care hospital.Methods: The retrospective descriptive study was conducted at Aga Khan University Hospital, Karachi, comprising data related to children below 15 years of age and treated between January 1997 and December 2006. Kaplan Meir survival curves were used to describe overall and event-free survival rates. Cox Proportional Hazards model was used to describe factors associated with death and relapse. SPSS 16 was the main statistical tool.Results: Of the total 121 children diagnosed with the condition, 79 (65.3%) were males; 86 (71.1%) patients were between 1-9 years of age; Immunophenotyping was done in 99 (81.81%) patients: 86 (87%) cases had precursor B and 13 (13.13%) had precursor T. Of the total, 106 (87.6%) patients opted for treatment, while 15 (11.6%) were lost to follow-up. Besides, 26 (21.7%) patients had at least one relapse; the most common site being bone marrow in 13 (50%) followed by central nervous system in 9 (36.6%). There were 20 (16.5%) deaths in the sample. Infection was the most frequent cause of death. The event-free survival and overall survival was 63% (n = 76) and 65% (n = 79) respectively.Conclusion: Through the clinical characteristics of children with acute lymphoblastic leukamia were similar to those reported in literature, the outcomes were inferior. The high rate of infections and relapse warrant better supportive care and risk-based approach

Acute myeloid leukaemia in children: experience at a tertiary care facility of Pakistan

Objective: To document the demographics and outcome of children with Acute Myeloid Leukemia (AML) treated at a tertiary care facility of Pakistan. Methods: A retrospective study was conducted at Aga Khan University on children (less than 15 years) diagnosed to have AML between January 2000 to May 2007.Total 40 cases were diagnosed out of which 37 charts were available for review. Results: The average age of presentation was 8.5±4.5 years and 75% were males. The most common presenting feature was fever in 83% followed by bleeding in 41% and pallor in 39%. Initial WBC of \u3e 100,000 was seen in 19% of patients. The most common FAB subtype was M4 39%. Twenty three patients underwent treatment out of which 12 patients are alive and in remission. Majority were followed up around 2 years and 6 months. Out of the 11 patients who died three had resistant disease, four relapsed and rest died due to sepsis mostly during induction. Conclusions: The most common sub type in our study is AML M4 although AML M2 is reported as predominant subtype. About a third of the patients could not start or complete therapy due to financial constraints. The overall survival for our patients who completed therapy was 52%

Cerebellar mutism syndrome after surgical resection of posterior fossa neoplastic lesions

Cerebellar Mutism Syndrome (CMS) is a well-described clinical entity that complicates surgeries for posterior fossa tumours; more so in children than adults. This review focuses on the current understanding of CMS, its incidence and risk factors. Incidence showed a variable range in retrospective studies due to variety of definitions. Risk factors can be classified as either modifiable including surgical technique, or non-modifiable which include tumour related factors. A positive correlation has been associated between tumour pathology, brain stem invasion and size of tumour at time of presentation with development of CMS

Childhood medulloblastoma

Medulloblastoma is the most common malignant brain tumour in children and is a major cause of mortality and morbidity, particularly in low- and middle-income countries. It has been risk-stratified on the basis of clinical (age, metastasis and extent of resection) and histological subtypes (classic, desmoplastic and anaplastic). However, recently medulloblastoma has been sub-grouped by using a variety of different genomic approaches, such as gene expression profiling, micro-ribonucleic acid profiling and methylation array into 4 groups, namely Wingless, Sonic hedgehog, Group 3 and Group 4. This new sub-grouping has important therapeutic and prognostic implications. After acute leukaemia, brain tumour is the second most common malignancy in the paediatric age group. The improvement in outcome of acute lymphoblastic leukaemia in low- and middle-income countries reflects the relative simplicity of diagnostic procedures and management. Unlike leukaemia, the management of brain tumours requires a complex multidisciplinary approach, including neuro-radiologists, neurosurgeons with a paediatric expertise, neuropathologists, radiation oncologists and neuro-oncologists. In addition, the equipment required for the diagnosis (magnetic resonance imaging scan, histological, molecular and genetic techniques) and the management (operating room, radiation facilities) is a limiting factor in countries with limited resources. In Pakistan, there are very few centres able to treat children with brain tumours. The current literature review was planned to provide an update on the management of this tumour

Glioblastoma multiforme involving conus medullaris in a child

Primary spinal cord glioblastoma multiforme involving the conus medullaris is an uncommon entity with poor outcomes. An aggressive multimodality treatment approach has been used, but prognosis remains same. There are no guidelines for the treatment of patients with spinal glioblastoma multiforme (GBM). We highlight the case of a child diagnosed with conal GBM. He was treated with definitive surgery followed by adjuvant concurrent chemoradiation. After completion of treatment, he showed a temporary symptomatic improvement, but later on his condition deteriorated. We elaborate the stepwise treatment approach employed in this patient

Pediatric brainstem gliomas: An institutional experience

Objective: The aim of this study was to analyze the clinical profiles and outcomes of pediatric brainstem gliomas treated at our institute.Methodology: We reviewed the files of 18 pediatric age group patients diagnosed with brainstem glioma at our institution. The following variables were recorded: age, sex, duration of symptoms, date of diagnosis, main clinical symptoms, Karnofsky performance status score, magnetic resonance imaging findings, histopathology findings, details of the treatment given, disease progression, and date of mortality/last follow-up. This data were then transferred to SPSS version 23 which was used for further analysis.Results: The mean age of our cohort was 8.6 years (range 3-15). There were 11 (61.1%) males and 7 (38.9%) females. There were 16 (88.9%) patients with diffuse intrinsic pontine gliomas (DIPGs), 1 (5.6%) patients with exophytic medullary gliomas, and 1 (5.6%) patient with midbrain/tectal glioma. Mean overall survival (OS) was 9.7 months. Mean progression-free survival (PFS) was 6.3 months. All patients with DIPG eventually passed away from their disease. Patients with DIPG who received radiotherapy had a longer OS and PFS than those who did not (9.8 and 6 months vs. 3.4 and 2.4 months). Diagnostic latency \u3e1 month was found to have a statistically significant longer progression-free interval.Conclusion: DIPGs in the pediatric population have a poor prognosis. Radiotherapy serves to increase survival time but is not curative

Evolution of systemic therapy in medulloblastoma including irradiation-sparing approaches

The management of medulloblastoma in children has dramatically changed over the past four decades, with the development of chemotherapy protocols aiming at improving survival and reducing long-term toxicities of high-dose craniospinal radiotherapy. While the staging and treatment of medulloblastoma were until recently based on the modified Chang\u27s system, recent advances in the molecular biology of medulloblastoma have revolutionized approaches in the management of this increasingly complex disease. The evolution of systemic therapies is described in this review

Intracranial tumors in children: A 10-year review from a single tertiary health-care center

Objective: Brain tumors are the second most common pediatric malignancy and the most common cause of cancer-related mortality and morbidities. Major advances in terms of surgery, radiation, and chemotherapy have led to better outcomes in developed countries. Delayed diagnosis, advanced disease at presentation, late referrals, nosocomial infections, delays to radiotherapy, and poor support services are the major reasons for poorer outcomes in developing countries. Little is known about the profile of brain tumors in Pakistan. This study aims to evaluate the epidemiology, management, and clinical outcomes of children with brain tumors in Pakistan in a single tertiary care center.Methods/Materials: All children (0-16 years) with primary CNS tumors from 2004 to 2014 at Aga Khan University Hospital were reviewed retrospectively for clinical data, demographics, radiological findings, management, and outcome.Results: One hundred seventy-five children were included in the study. Male to female ratio was 1.4:1. Most of the patients were in 5-10 years age group (38.9%). Most common presenting complains were headache 115 (65.7%) and vomiting 100 (57.1%). Predominant site was infratentorial 93 (53%). Glial tumors were 105 (60%) followed by embryonal 40(22.9%), craniopharyngiomas 25 (14.3%), and germ cell 1 (0.6%). Astrocytomas (25.7%) were the most common glial tumors while medulloblastoma (15.4%) was the most common embryonal tumor. Majority of the patients underwent surgical resection (78.8%). Radiation was given to 47 (26.8%) patients. A half of the patients, 89 (50%), were lost to follow-up. Forty-two (24%) patients expired, 20 (11.4%) are alive with residual disease while 15 patients (8.5%) were cured with no evidence of recurrence and regular follow-ups.Conclusion: This is the only study from Pakistan showing demographics of the childhood brain tumors. Significant improvement needs to be made for timely diagnosis, early referrals, and collaborated team efforts with multidisciplinary tumor board to improve outcome

Case of embryonal tumor multilayered rosettes in a patient with neurofibromatosis type 1

Background: ETMR is a unique and highly malignant brain tumor mostly occurring in infants. This report provides a comprehensive overview of the clinical presentation, histological aspects, radiological features, and therapeutic options of ETMR. Being the first report on the co-occurrence of NF1 with ETMR, it highlight the challenges of managing a patient with complex medical conditions.Case report: We present a case of a 3 and 1/2-year-old girl with neurofibromatosis type 1 (NF1), later diagnosed with a supratentorial brain tumor reported as an embryonal tumor with multilayered rosettes (ETMR), along with possible co-occurrence of constitutional mismatch repair deficiency (CMMRD) on immunohistochemistry (IHC); however, germline testing was not performed. Even though NF1 can be associated with tumors such as gliomas, the literature has no previous case reports of ETMR coexisting with NF1.Conclusion: Exploring the link between NF1 and ETMR with CMMRD is crucial to improving and establishing more treatment protocols. Therefore, reporting each case\u27s unique features would be essential in developing appropriate treatment protocols