Prophylactic Use Of Levofloxacin During Induction Of Acute Lymphoblastic Leukaemia In Children-Experience From Pakistan.

To assess whether prophylactic use of Levofloxacin would reduce the number of febrile neutropenia episodes during the induction phase, a single-centre, case-control study was carried out. Data was collected prospectively of patients who received Levofloxacin prophylaxis during the induction chemotherapy from September 2019 till October 2020. The cases were compared with historical controls who did not receive antibiotics prophylaxis. A total of 121 patients were enrolled, among which 61 patients were cases, whereas 60 patients were controls. The patients who received Levofloxacin prophylaxis had lower rate of febrile neutropenia episodes than patients who did not receive any prophylaxis (p≤0.01) (odds ratio [OR]:0.23, CI 95%). No significant difference in induction mortality was seen between the two groups (p≤0.14). Levofloxacin prophylaxis reduced the rate of febrile neutropenia episodes among patients, but it did not affect the infection related mortality.

Lymphomatoid Granulomatosis: A Case Report and Literature Review of a Rare Pediatric Disorder From Pakistan.

BACKGROUND: Lymphomatoid granulomatosis (LYG) is a rare pediatric disorder driven by the Epstein-Barr virus and is considered as a part of the lymphoma spectrum. It is mostly associated with immune deficiency and patients on immunosuppressive therapy, especially with acute leukemia. It can present as a multisystemic disease, diagnosed on biopsy as atypical lymphocytes with an angiocentric pattern against a background composed of histiocytes, neutrophils, and extensive T-cell infiltration. OBSERVATION: We report 3 cases of children with Lymphomatoid granulomatosis, one with Langerhans cell histiocytosis. CONCLUSION: Combination chemotherapy was used for the treatment of Lymphomatoid granulomatosis; however, the prognosis is guarded. One of 3 patients is alive and in remission on the last follow-up visit at 15 months.

10-Year-Old Pakistani Boy With Multiple Malignancies: Loss Of Pms2-Constitutional Mismatch Repair Deficiency.

Constitutional Mismatch repair deficiency (CMMRD) is a cancer predisposition syndrome. Four main common malignancies seen are, haematological, brain tumours, colorectal cancers, and intestinal polyps. We are reporting a 10-year-old boy with CMMRD; diagnosed with hematological malignancies, followed by low grade glioma in thalamus. There was loss of PMS2, whereas immunostaining was retained for MLH1, MSH2 and MSH6. Early diagnosis of CMMRD is crucial especially in countries like Pakistan, where consanguineous marriages are common. Increasing awareness among the physicians will help in early diagnosis, surveillance and in providing appropriate genetic counselling to the family.

Clinical course, long-term outcomes, and chemotherapy toxicity profile in B-cell Non-Hodgkin Lymphoma in children: Single institution experience of Pakistan.

OBJECTIVE: To analyse the disease presentation, clinical course and long-term outcomes of children diagnosed with B-cell non-Hodgkin lymphoma. Methods: The retrospective descriptive study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan and comprised data of patients diagnosed with B cell non-Hodgkin lymphoma between January 2012 and December 2016, with follow-up time of 4 years post-treatment. Data was collected from the institutional database. Data was analysed using SPSS 20. RESULTS: Of the 286 patients, 217(75.6%) were males and 69(24.1%) were females. The overall mean age at presentation was 7.6±4.1 years (range: 1-16 years). Burkitt lymphoma was diagnosed in 194(67.8%) patients, and diffuse large B cell in 83(29.0%). Majority of patients had presented with stage III disease 159(55.6%). Complete remission was achieved in 173(60.5%) patients, while 90(31.5%) died during treatment. The 4-year overall survival observed was 67.1%, whereas event-free survival was 60.5%. Conclusion: Majority of the paediatric patients presented with extensive disease. Measures are needed for early recognition, identification, and prompt referral to paediatric cancer institute.

Clinical Outcome of paediatric ewing sarcoma and significance of pathological necrosis for mortality after neoadjuvant chemotherapy: Single institutional study.

OBJECTIVE: To determine the clinical outcome and significance of pathological necrosis after neoadjuvant chemotherapy. METHODS: The retrospective study was conducted in Shaukat Khanum Memorial Cancer Hospital and Research Center and comprised data from January 2010 to December 2015 related to young with newly diagnosed Ewing sarcoma on histopathology. Data was collected on patients aged <20 years of either gender along with primary tumour site, metastatic status, tumour volume, mode of local therapy, degree of necrosis post-surgery, tumour margins after resection, outcome at the end of treatment and at last follow-up visit. Tumours were categorised as grade I = little or no necrosis, grade II = 50-90% necrosis, grade III = 90-99% necrosis, and grade IV = 100% necrosis. Data was analysed using SPSS 20. RESULTS: Of the 124 patients, 89(72%) were non-metastatic; 35(28%) were metastatic; 37(29.8%) underwent surgery; 58(46%) received radiotherapy; 7(5.6%) received both surgery and radiotherapy; 22(17.7%) received no treatment. Histopathology report post-surgery showed little grade 1 necrosis in 10(8%) patients, grade II in 8(6.5%), grade III in 8(6.5%) and grade IV in 14(11%). Event-free survival in grade IV necrosis was 93% in 14 (11.3%) patients, EFS in grade III necrosis was 71% in 8(6.5%) patients , EFS in grade II necrosis was 22% seen in 9(7.3%) patients and EFS in grade- I necrosis was 35% seen in 14 (11.3%) patients. Overall survival in grade IV necrosis was 93% in 14 (11.3%) patients, OS in grade III 75% seen in 8(6.5%), OS in grade II 25% seen in 9(7.3%) and OS in grade I was 50% in 14(11.3%) patients. Event-free survival was 48 (38%) patients and overall survival of Ewing sarcoma patients was 52 (46.6%) patients respectively. CONCLUSION: Tumour necrosis and histopathological changes post-surgery were found to have great impact on survival outcome in Ewing Sarcoma.

Training pediatric hematologist/oncologists for capacity building in Ethiopia.

PURPOSE: A considerable barrier to global pediatric oncology efforts has been the scarcity and even absence of trained professionals in many low- and middle-income countries, where the majority of children with cancer reside. In 2013, no dedicated pediatric hematology-oncology (PHO) programs existed in Ethiopia despite the estimated annual incidence of 6000-12000 cases. The Aslan Project initiative was established to fill this gap in order to improve pediatric cancer care in Ethiopia. A major objective was to increase subspecialty PHO-trained physicians who were committed to practicing locally and empowered to lead programmatic development. METHODS: We designed and implemented a PHO training curriculum to provide a robust educational and clinical experience within the existing resource-constrained environment in Ethiopia. Education relied on visiting PHO faculty, a training attachment abroad, and extraordinary initiative from trainees. RESULTS: Four physicians have completed comprehensive PHO subspecialty training based primarily in Ethiopia, and all have remained local. Former fellows are now leading two PHO centers in Ethiopia with a combined capacity of 64 inpatient beds and over 800 new diagnoses per year; an additional former fellow is developing a pediatric cancer program in Nairobi, Kenya. Two fellows currently are in training. Program leadership, teaching, and advocacy are being transitioned to these physicians. CONCLUSIONS: Despite myriad challenges, a subspecialty PHO training program was successfully implemented in a low-income country. PHO training in Ethiopia is approaching sustainability through human resource development, and is accelerating the growth of dedicated PHO services where none existed 7 years ago.

Response rates, long term outcomes and toxicity profile of gemcitabine and vinorelbine based outpatient chemotherapy regimen in primary progressive and relapsed childhood Hodgkin lymphoma.

This study aimed to determine response rates, overall survival (OS), event-free survival (EFS) and toxicity profile of an outpatient chemotherapy regimen based on gemcitabine and vinorelbine (GV) for relapsed childhood Hodgkin lymphoma (HL). This was a retrospective study that included 41 patients up to the age of 18 years with relapsed HL. Twelve patients (29%) had primary progressive disease (PPD), 6 (15%) had early relapse (ER) and 23 (56%) had late relapse (LR). The overall initial response rate was 83% (LR: 87%, ER: 83%, PPD: 75%. p-value: .2). Three-year combined OS was 80% (LR: 89%, ER: 80%, PPD: 65%. p-value: .07) and EFS 71% (LR: 86%, ER: 62%, PPD: 47%. p-value: .01). There were no toxic deaths. Febrile neutropenia was observed in four patients (9.6%) and lung toxicity in 1 patient (2.4%). This study suggests that outpatient GV is an effective and low toxicity salvage regimen for relapsed childhood HL.

Retrospective analysis of clinical features and treatment outcomes of children with Hodgkin's Lymphoma treated with different chemotherapy protocols at a tertiary care center in Pakistan.

PURPOSE: Hodgkin lymphoma (HL) is one of the most curable paediatric cancers, with long-term survival rates now exceeding 90% after treatment with chemotherapy alone or combined with radiotherapy (RT). Treatment options for Hodgkin's Lymphoma differ among various study groups and there is still no consensus regarding the standard treatment for Hodgkin's lymphoma. Taking into account the impact of treatment-related mortality in low- and middle-income countries we propose to study the the clinical features and treatment outcomes by using different chemotherapy protocols in Hodgk in s' s Lymphoma children's at Shaukat khanam hospital Lahore.. METHODS: Clinical data from a large regional cancer center Pediatrics patients with Hodgkin's Lymphoma from January 2009 till December 2015 was retrospectively collected after Institutional Review Board (IRB) approval. RESULTS: A total of 748 patients were reviewed retrospectively. Mostly (45%) were in 6-10 years age group. Male showed predominance ,male to female ratio was 4:1. B symptoms were present in 51%, bulky disease in 44% and ESR was more than 30mm in 26% of patients. CD 30 was positive in 95%, Bone marrow involved in 13% of patients. Stage I in 8%, stage- II in 27%, stage -III in 39% and stage IV in 26% was seen. COPDAc/ABVD was given in 412 patients, CHLVPP/ABVD in 176 patients, OEPA/COPP in 57 patients, OEPA in 35 patients, OEPA/COPDAC in 33 Patients and remaining 33 received various chemotherapy protocol combination. XRT was given in 17% of patients. Of these 86% of patients were alive ,5% patients died , 3% patients abandoned, 6% patients relapsed ,3% patients progressed while on chemotherapy. Five years Overall survival was 94% and 5 Years Event free survival was 91%. Minimum haematological and other toxicity was seen in patients who had received COPDac/ABVD when compared to other regimen. CONCLUSIONS: Hodgkin's lymphoma patients had good outcome with different chemotherapy regimens, however our experience showed that the COPDac/ABVD regimen wass better tolerated with minimum toxicity.

Malnutrition, Sepsis, and Tumor Lysis Syndrome Are Associated with Increased Rate of Acute Mortality in Mature B Cell Non-Hodgkin Lymphoma in a Pediatric Population-Study from Tertiary Care Hospital in Pakistan.

BACKGROUND: Outcomes of pediatric mature B cell non-Hodgkin's lymphoma in resource-challenged countries are negatively affected by an increased rate of early and toxic deaths. Aim of this study is to assess the rate of acute mortality and define significant risk factors present in children with mature B cell non-Hodgkin's lymphoma. METHODS: A retrospective analysis was done of patients with B cell non-Hodgkin's lymphoma from January 2012 till December 2016. Risk factors studied for acute mortality were malnutrition, stage, prior surgery with open laparotomy, lactate dehydrogenase levels, tumor lysis syndrome, sepsis, and fungal infection. RESULTS: A total of 233 patients were enrolled in the study. Eighty-five (36.4%) were below 15th percentile weight for age. Treatment was started in 226 patients. Eighty-eight percent of children showed a 20% response after COP pre-phase. Tumor lysis syndrome was developed in 20.6% (n = 48) children and 42.9% (n = 100) patients had sepsis, 71/100 patients had culture-proven sepsis. 19.7% (n = 46) patients developed fungal infection. There was 19.7% (n = 46) acute mortality. The most common cause of death was sepsis (n = 22, 47.8%) followed by acute renal failure secondary to tumor lysis syndrome. On multivariate analysis, three independent variables found significant for early death are malnutrition, sepsis, and tumor lysis syndrome. CONCLUSION: Rate of acute mortality in mature B cell NHL is high in our set up and significant risk factors are tumor lysis syndrome, sepsis, and malnourishment at the time of presentation.

A Single Institution's Experience with Cytogenetic and MRD Outcomes in Pediatric Acute Lymphoblastic Leukemia.

OBJECTIVE: To determine the frequency of cytogenetic type and its significance in the prognostic outcome of the pediatric patients in acute lymphoblastic leukemia (ALL), aged 1 to 15 years, and also determine the importance of minimal residual disease (MRD) in the management of the condition. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Pediatric Oncology Ward, Shaukat Khanum Cancer Hospital, Lahore, from January 2015 to July 2017. METHODOLOGY: Patients aged 1-15 years, diagnosed with ALL, were included. Studied variables were cytogenetic type and MRD outcome in patients with ALL. Patients under one year of age and more than 15 years, or those having comorbidities, were excluded. RESULTS: Total 150 patients' data were retrieved from the Hospital database. One hundred and thirty-three belonged to age 1 to 5 years group (89%) and 17 (11%) were in 5 to 10 years group. The mean age of the patient was 4.3 +3.1 years. One hundred and two (68%) were males; whereas, 48 (32%) were females. Pre B acute lymphoblastic leukemia was diagnosed in 139 (93%) patients and 11(7%) were diagnosed with Pre T acute lymphoblastic leukemia. Standard risk was observed in 120 (80%) patients and 30 (20%) patients were on high risk as per National Cancer Institute (NCI) Guidelines. Regimen A was used in 125 (83.3%), Regimen B in 16 (10.7%), and Regimen C in 9 (6%) patients. BCR-ABL was positive in 2 (1.30%), TEL-AML in 68 (45%), MLL in 5 (3.30%), and normal in 54 (36%). MRD at day 29 was negative in 40 (93%) and positive in 3 (7%). The karyotyping was done in 128 (85%) patients, out of which 68 (53%) were hyperploids, 41 (32%) euploid, and 19 (15%) were hypoploid. Death was observed in 22 (15%) patients. Nineteen (86%) deaths were due to fungal and bacterial sepsis; and disease-related deaths were noted in 3 (14%) patients. CONCLUSION: The role of MRD and cytogenetics in risk assessment has improved in the early prognosis determination.

Fungal Infections In Paediatric Patients With Acute Lymphoblastic Leukaemia While On Induction Chemotherapy.

BACKGROUND: Acute Lymphoblastic Leukaemia (ALL) is one of the most common haematological malignancies seen in children. Despite steadily improving long-term outcomes, infections remain a major cause of morbidity and mortality in children receiving therapy for leukaemia. The incidence and risk of invasive fungal infections (IFIs) continue to rise. In some settings, IFIs caused by moulds are more frequent than those caused by yeasts, and Aspergillus spp. is the most common pathogens. The aim of the study was to determine the frequency, type of fungal infection seen during induction chemotherapy and outcomes.. METHODS: This observational retrospective study was conducted in paediatric oncology department at Shaukat Khanum Cancer Hospital Lahore from January 2015 to December 2016 after taking International research board (IRB) approval. The study includes all the patients aged 1-15 who were diagnosed with acute lymphoblastic leukaemia while on induction chemotherapy. The data was retrieved of 165 patients from the hospital database after informed written consent.. RESULTS: The mean age of the patients was 4.6±2.80 with range 1-15years. Total 154 (93%) of the children were of age between 1-5 years whereas only 11 (6.7%) were between 5-10 years. Male sex was predominant in 117 (70.9%) and 48 (29.1%) were girls. Pre-B Acute lymphoblastic leukaemia was diagnosed in 93.3% of the patients and rest 11 (6.7%) were diagnosed with Pre-T Acute lymphoblastic leukaemia. NCI Standard risk patients were 132 (80%) and 33 (20%) were stratified as high risk. Fungal infections were documented in 18 (11%) patients out of which 7(39%) were probable infections, and only 11 (61%) were proven fungal infections. Aspergillus was the commonest organism in 5 (28%) patients. Death was observed in 21 (13%) patients and causes were sepsis due to infections in 18 (86%) out of which fungal infections were 11(61%), bacterial 4(22%), combine bacterial and fungal 3(17%). Remaining 3 (14%) patients death causes include, neutropenic colitis was observed in first patient, second patient died of infection without any identifiable focus, and third patient died due to chemotherapy related toxicity.. CONCLUSIONS: Our study concludes that the fungal infection was the most common cause of mortality in induction in our patients. A prospective study in the form of clinical trial is needed to see if use of prophylactic antifungal can improve outcomes in our setting.

Excellent Outcomes of Grey Zone Lymphoma: Case Series of Paediatric Patients Treated at a Single Centre.

Our objective was to review clinical presentation, treatment protocol used and its efficacy and effectiveness in patients of grey zone lymphoma during last 5 years at our centre. A retrospective chart review of children below 18 years of age was done from 2011 to 2016. A proforma was devised for this purpose and the findings of cases detected during the specified period were noted over it. We treated 4 cases, all with a diagnosis of Grey Zone Lymphoma of ages 13, 13, 15 and 7 years at presentation and all were males. Two patients had stage II and the other two had stage III disease. None had a mediastinal mass. All patients were treated according to UKCCSG NHL guidelines. Tumour lysis syndrome was not observed in any child. All tolerated chemotherapy very well and achieved complete remission. No patient died of the disease or any complication and all are well on their latest follow ups. To conclude from excellent outcomes in our case series, we recommend that children with Grey Zone Lymphoma should be treated according to Non-Hodgkin Lymphoma treatment guidelines. However we need to have more prospective studies, so that treatment guidelines can be established.

Six-year-old boy with mediastinal mass.

Lymphoblastic lymphomas account for 20-30% of all non-Hodgkin lymphomas (NHL) in children, and most cases of childhood lymphoblastic lymphoma are T-cell type (T-LL). T-LL occurs most frequently in late childhood and adolescence; with male predominance of 2:1.We present a paediatric case with a right sided mediastinal mass causing mediastinal shift diagnosed as T-LL.