Childhood non-Hodgkin Lymphoma Research Articles

Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells.

Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells. In silico analyses of patient samples, combined with in vitro experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3-kinase (PI3K) pathway. Isatuximab was found to be more effective than daratumumab in disrupting B-cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes. The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20years. Limited data exist on CMMRD-associated lymphomas and their outcome. We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first. The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%. Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.

Potential diagnostic and prognostic biomarkers of pediatric Burkitt lymphoma identified through miRNA expression profiling.

Pediatric Burkitt lymphoma (pBL) is the most common non-Hodgkin lymphoma in children. These patients require prompt diagnosis and initiation of therapy due to rapid tumor growth. The roles of tumor tissue and circulating microRNAs (miRNAs) in the diagnosis or prognostication have not been fully elucidated in pBLs. Differentially expressed (DE) miRNAs were identified with microRNA sequencing (miRNA-Seq) in tumor tissues and plasma of diagnostic pBLs. The diagnostic potential of total miRNA concentrations and overexpressed miRNAs were evaluated through receiver operating characteristic (ROC) analyses. Log-rank test was employed to evaluate survival differences associated with DE miRNAs. Selected miRNA expressions were cross-validated with quantitative reverse transcription PCR (qRT-PCR). Total circulating cell-free miRNAs were higher in pBL cases compared to controls. Cancer-associated pathways were enriched among miRNAs differentially expressed in pBL tumor tissues. Several upregulated miRNAs in pBL tumors demonstrated high diagnostic potential. Similarly, ROC analysis of overexpressed plasma miRNAs revealed circulating cell-free or exosomal miRNAs that can distinguish pBLs from control cases. Indeed, integrative analysis of overexpressed circulating exosomal miRNAs showed an enhanced diagnostic potential for certain triple combinations. Kaplan-Meier analyses of DE miRNAs in tumor tissues identified miRNAs predicting overall survival. Differentially expressed miRNAs in tumor tissue and plasma of pBL have the potential to improve diagnosis and prognosis. Differentially expressed miRNAs in treatment-naive pediatric Burkitt lymphoma cases have diagnostic or prognostic biomarker potential. This is the first study that applied miRNA-Seq on treatment-naive pediatric Burkitt lymphoma cases for identification of differentially expressed miRNAs both in tumor tissue and plasma samples with diagnostic potential. Through systematic analysis of differentially expressed miRNAs, tumor tissue miRNAs associated with the overall survival of pBLs have been discovered. The clinically significant, differentially expressed miRNAs identified in pediatric Burkitt lymphoma cases can potentially improve the current tissue-based or non-invasive clinical practice in terms of diagnosis or prognostication.

Indolent B-cell non-Hodgkin lymphomas in children: high association with inborn errors of immunity

Indolent lymphomas are rare in children and mostly consist of pediatric type follicular (PTFL) and pediatric marginal zone lymphomas (PMZL) and extranodal marginal zone lymphoma (ENMZL). Twenty children with indolent lymphoma (10 PTFL, 6 PMZL, 3 ENMZL, 1 mixed type) among 307 Non-Hodgkin Lymphoma (NHL) were retrospectively evaluated. The mean age of the entire group was 10.4 ± 4.4 and was significantly lower in PTFL than in PMZL. Seven patients (35%) had an associated inborn error of immunity (IEI) which was higher than that seen in aggressive lymphomas (5.9%) (p < 0.0001). Seventeen patients (85%) had stage I/II disease. Two patients received no treatment after surgery. Eleven patients were treated only with 3-6 courses of rituximab. Four patients received 3-6 courses of R-CHOP protocol. The prognosis was excellent Five years overall and event-free survivals were 100% and 85%, respectively.

Therapy for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma in Children, Adolescents, and Young Adults.

Despite excellent cure rates among children, adolescents, and young adults (CAYAs) with mature B-cell non-Hodgkin lymphomas (B-NHLs) treated with chemoimmunotherapy, CAYAs with relapsed/refractory B-NHL remain difficult to treat, with a dismal prognosis. Reinduction and subsequent therapeutic management are not standardized. The armamentarium of active agents against B-NHL, including antibody-drug conjugates, monoclonal antibodies, checkpoint inhibitors, T-cell engagers, CAR T cells, CAR-natural killer (CAR-NK) cells, and cell signaling inhibitors, continues to expand. This article reviews current management practices and novel therapies in this difficult to treat population.

A Case of Childhood Non-Hodgkin's Lymphoma Presenting as Isolated Inguinal Lymphadenopathy

Inguinal lymphadenopathy is a common condition encountered in routine clinical practice. It can be associated with various causes such as infections, inflammatory conditions, and neoplastic processes. We report the case of a young female presenting with an inguinal swelling with active discharge, which was initially suspected to have bacterial lymphadenitis, but subsequently diagnosed with non-Hodgkin’s lymphoma. Such an atypical presentation of a hidden malignancy is very rare and has never been reported as per our knowledge.

Laboratory and clinical features of tumor lysis syndrome in children with non-Hodgkin lymphoma and evaluation of long-term renal functions in survivors

ObjectiveThe purpose of our study is to investigate the laboratory and clinical features of tumor lysis syndrome (TLS) and acute kidney injury (AKI) in childhood non-Hodgkin lymphomas (NHL) and to reveal their impact on long term kidney function in survivors.MethodsOur single-center retrospective study included 107 patients (0-18 years old) with NHL who were admitted and treated at our hospital between 1998 and 2020. The relationship between TLS and age, gender, histopathological subgroup, tumor stage, lactate dehydrogenase (LDH) level at presentation, bone marrow and kidney involvement were assessed. The long-term renal functions of the patients were investigated.Results80.3% of the patients were male with a median age of 9.8 years. The most common detected histopathological subgroup was Burkitt lymphoma. Hyperhydration with or without alkalinisation, and allopurinol were used in first-line treatment and prophylaxis of TLS. Laboratory TLS and clinical TLS was observed in 30.8% and 12.1% of patients, respectively. A significant correlation was found between young age, advanced stage, high LDH level at presentation, and TLS. AKI was observed in 12.1% of the patients. When the glomerular filtration rate values of the patients at the first and last admissions were compared after an average of 6.9 years, a mean decrease of 10 mL/min/1.73 m2 was found. It was not, however, found to be statistically significant.ConclusionLower age, advanced stage, and high LDH level at presentation were found to be risk factors for TLS in our study. Long-term renal function loss was not observed in the survivors who received early and careful prophylaxis/treatment for TLS. The survivors are still being followed up.

Trends in physical functioning in acute lymphoblastic leukemia and non-Hodgkin lymphoma survivors across three decades.

The impact of changes in therapy for childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) on the prevalence of physical performance limitations and participation restrictions among survivors is unknown. We aimed to describe the prevalence of reduced function among ALL and NHL survivors by treatment era. Participants included survivors of childhood ALL and NHL, and a cohort of their siblings, participating in the Childhood Cancer Survivor Study (CCSS). Physical function was measured using questionnaire. The prevalence of reduced function was compared to siblings using generalized estimating equations, overall and stratified by treatment decade. Associations between organ system-specific chronic conditions (CTCAE v4.03) and function were also evaluated. Among 6511 survivors (mean age 25.9years (standard deviation 6.5)) and 4127 siblings, risk of performance limitations (15.2% vs. 12.5%, prevalence ratio [PR] = 1.5, 95%CI = 1.3-1.6), restrictions in personal care (2.0% vs. 0.6%, PR = 3.1, 95% CI = 2.0-4.8), routine activities (5.5% vs. 1.6%, PR = 3.6, 95% CI = 2.7-4.8), and work/school attendance (8.8% vs. 2.1%, PR = 4.5, 95% CI = 3.6-5.7) was increased in survivors vs. siblings. The prevalence of survivors reporting reduced function did not decrease between the 1970s and 1990s. The presence of neurological and cardiovascular conditions was associated with reduced function regardless of treatment decade. Despite changes in therapy, the prevalence of poor physical function remained constant between the 1970s and 1990s. The CCSS clinical trial registration number is NCT01120353 (registered May 6, 2010). Our findings support screening for reduced physical function so that early interventions to improve physicalperformance and mitigate chronic disease can be initiated.

A Systematic Review on Childhood Non-Hodgkin Lymphoma: An Overlooked Phenomenon in the Health and Research Sector of Bangladesh.

Globally, childhood cancer, particularly non-Hodgkin lymphomas (NHLs), is a prevalent concern. However, the difficulty becomes even more distressing in lower-middle-income nations such as Bangladesh. The insufficiency of research, resources, inadequate guidelines, expensive treatment costs, and specialized knowledge exacerbate the challenges associated with the treatment of certain types of cancers.Our investigation looked extensively into the circumstances prevailing in Bangladesh, with the objective of providing a comprehensive overview of the current status and approaches to managing NHL in the country. Through this work, our intention was to illuminate the domains that require immediate focus and assistance. To get insight into the present state of NHL in Bangladesh, our analysis focused on a selection of seven research articles and two case reports published between 2018 and 2023. In order to ensure the integrity and consistency of our review, we conducted a detailed selection procedure, employing the systematic PRISMA review methodology. From a pool of 294 papers, we selected the ones that met our predetermined criteria. These papers were sourced from reputable academic databases, such as Google Scholar and PubMed.The findings of our study indicate a higher prevalence of NHL among children in Bangladesh compared to Hodgkin lymphoma (HL). Additionally, this phenomenon exhibits a higher prevalence among male individuals. Our study revealed that in Bangladesh, there is a lack of a dedicated guideline or research center specifically focused on NHL. Additionally, the number of research centers and research dedicated to cancer treatment as a whole is limited.Our research aims to offer a complete analysis of NHL in the context of Bangladesh, with the intention of offering valuable guidance to healthcare professionals and policymakers. The utilization of our research outcomes has the potential to enhance patient care, facilitate the development of more effective clinical protocols, and promote greater accessibility and affordability of therapies. This has the potential to provide improved cancer care not only in Bangladesh but also in other comparable contexts worldwide.

Clinical profile and outcome of children with anaplastic large cell lymphoma treated with short-course chemotherapy – ten years experience from a tertiary care center in a LMIC

Anaplastic large-cell lymphoma (ALCL) constitutes 10–15% of non-Hodgkin lymphoma in children. With short-course chemotherapy, outcome has improved up-to 90% in developed-countries. There is limited-data on outcome of pediatric ALCL treated with ALCL99 protocol from low-middle income countries. Children ≤14 years, diagnosed with ALCL between 1st January 2007 and 31st December 2016 were analyzed. Details regarding clinical-presentation and treatment were recorded and outcome was analyzed. Fourteen-children were diagnosed. Median-age was 114 months (range 24 – 162 months). Male:female ratio was 3.6:1. Stage-I, II and III disease was seen in three (21.4%), three (21.4%), and eight (57.1%) children, respectively. Low, standard and high-risk disease was seen in two (14.2%), six (42.9%) and six (42.9%), respectively. All children were treated using ALCL99 protocol. Three (21.4%) children had disease-progression/relapse and five (35.7%) died (three from treatment-related mortality, and two from disease). At median follow-up of 54-months, four-year EFS and OS were 64.3% and 64.3%, respectively. Log-rank test demonstrated female gender (p = 0.005), stage-III disease (p < 0.001), visceral-organ involvement (p = 0.035), high-risk disease (p = 0.016) and, serum albumin ≤3.5 g/dL (p = 0.031) associated with significantly worse 4-year EFS. Cox-regression analysis demonstrated female gender associated with poor EFS (p = 0.02) and female gender and visceral-organ involvement associated with poor OS (p = 0.02, p = 0.011, respectively). Good survival could be achieved for children with ALCL using uniform treatment protocol in a resource-limited setting, especially among low and standard-risk children. Female-sex, high-risk disease, stage-III disease, visceral organ involvement and low albumin levels were associated with poor outcome, however these findings need to be corroborated in larger studies.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Minimal disease determination might serve for risk stratification, response evaluation and follow-up disease monitoring in childhood Non-Hodgkin lymphomas. Besides helping to judge minimal residual disease (MRD) during therapy, detection of minimal disseminated disease (MDD) at diagnosis may be of prognostic value itself. However, different subtypes, high cure rates, low patient numbers, limited initial tumour material and early progression pose challenges. Methods: Pubmed literature search on MDD and MRD in pediatric lymphomas. Results: Current clinical applications of minimal disease determination differ between the subtypes. For lymphoblastic lymphomas, both flow-cytometry detecting aberrant immunophenotypes and PCR-based assays for TCR- or Ig-rearrangements have been used for minimal disease measurement. A prognostic value of MDD could not be clearly established yet. MRD has not been analysed in larger patient cohorts so far. In Burkitt-lymphoma and -leukemia, MYC-Ig-fusion sequences or Ig-rearrangements enable minimal disease detection. While conflicting data on the role of MDD as risk factor for Burkitt lymphoma have been published, the prognostic value of early MRD in Burkitt leukaemia treated by risk-adapted chemotherapy has been described by two study groups. However, its role in the rituximab-era needs to be confirmed. In ALK-positive anaplastic large cell lymphoma (ALCL), MDD and MRD determined by qualitative or quantitative PCR for ALK-fusion transcripts are validated independent prognostic parameters. They are standard of care parameters assessed in routine clinically practice and used for patient stratification in clinical studies. Early MRD might even serve as endpoint for clinical trials and for guiding individual therapy. Conclusions and future outlook: Validation of MDD and MRD as prognostic parameters is required for all subtypes but ALCL. Next-generation sequencing based methods and the use of circulating cell-free tumour DNA as medium may provide new options and applications for minimal disease evaluation in childhood lymphomas. Keywords: diagnostic and prognostic biomarkers, minimal residual disease, non-Hodgkin (pediatric, adolescent, and young adult) No conflicts of interests pertinent to the abstract.

Spinal Cord Compression Revealing a Case of Metastasis of Burkitt Lymphoma

Burkitt lymphoma is the most frequent non-Hodgkin lymphoma in children and adolescents. The disease can involve all organs, although spinal cord involvement in the Burkitt lymphoma is exceptional and only a few cases are reported. We report a case of Burkitt lymphoma revealing by spinal cord compression in a 4-year-old patient. Magnetic resonance imaging (MRI) of the spine revealed a mass in the spinal intradural extramedullary space with severe spinal canal stenosis in T6-T9. Neuromeningeal involvement in Burkitt's lymphoma often represents a secondary location and defines an advanced stage of the disease. The child responded well to chemotherapy and is on remission.

Pediatric Non-Hodgkin Lymphoma: Ten-Year Experience with Berlin-Frankfurt-Munster (BFM) Protocols from a Tertiary Care Hospital in Turkey

Objective: Progress in therapy of childhood non-Hodgkin lymphoma (NHL) is one of the stunning success stories of the past two decades. In developed countries, more than 80% of children with NHL can now be cured with modern therapy, even patients with widely disseminated disease. The aim of this study is to analyze all NHL patients who were treated in a single tertiary center in Turkey. Methods: An analysis of data of children with NHL, diagnosed and treated between 2003 and 2012 according to the original Berlin-Frankfurt-Munster (BFM) protocol in Kocaeli University Pediatric Oncology Department was carried out. &#x0D; Results: Forty-seven children were eligible for analysis. Mean age at diagnosis was 9.6 years with a male: female ratio of 1.9. Thirty-one patients (66%) were mature B-cell NHL with 23 patients (48.9%) Burkitt lymphoma, 7 patients (14.8%) diffuse large B-cell lymphoma, 1 patient (%2) primary mediastinal large B-cell lymphoma; 13 patients (27.6%) were lymphoblastic lymphoma with 11 patients (23.3%) T-lymphoblastic lymphoma and 2 patients (4.2%) B-lymphoblastic lymphoma, and also 3 patients (6.3%) were mature-T cell lymphoma-anaplastic large cell lymphoma. Four-year event-free survival was 78.7% and overall survival was 80.8%. &#x0D; Conclusion: These results with BFM protocol administration reflect good treatment outcome in our patients.

The treatment of relapsed/refractory anaplastic large cell lymphoma expressing the anaplastic lymphoma kinase: a single-center experience

The treatment of relapsed/refractory anaplastic large cell lymphoma expressing the anaplastic lymphoma kinase: a single-center experience

I-FISH Guided Cytogenetic Study of Non-Hodgkin Lymphomas in Children and Adolescents: Correlation with Etiology and Outcome

Introduction: Pediatric non-Hodgkin lymphomas (NHLs) comprise approximately 10% of all childhood cancers. The diagnosis requires extensive workup with multiple ancillary studies. Genetic testing using fluorescence in situ hybridization (FISH) is a cytogenetic approach that is often utilized in pediatric NHL. Patients and Methods: Our study included 146 children (113 boys-33 girls), aged 0.33-17.8 years (median 9.16 years), with NHL diagnosis based on histopathology (table 1). The histological diagnosis was based on the complete microscopic and immunohistochemical study of infiltrated tissue. Touch imprints from the diagnostic biopsy samples were further investigated with i-FISH (table 2). Results: In all BL cases MYC gene rearrangement was identified. At least one additional chromosomal aberration was also found in 47 patients. Six hyperdiploid cases were identified among 72 children (8.3%), with at least 3 chromosomes involved. Interestingly, there were no cases of refractory disease, relapse, or death among hyperdiploid patients, and their overall survival (OS) was comparable to that of MYC rearrangement subgroup, a unique finding. Among LBL patients, a high frequency of 9p21 region deficiency was found, as in Acute Lymphoblastic Leukemia (ALL). Also, the chromosomes most frequently involved in hyperdiploid B-LBL (X,17,21) were identical to chromosomes commonly overrepresented in ALL. In contrast, the absence of cases positive for ETV6/RUNX1 hybrid gene is surprising. Possibly, the incidence of the most common cytogenetic atypias is different between leukemia and lymphoma. Of note, the two patients with KMT2A rearrangement achieved complete remission after first-line therapy. Finally, we identified cases with a normal karyotype but existing cytogenetic atypia demonstrable by i-FISH exclusively in LBLs. ALK gene rearrangement was found in all ALCL patients while no MYC gene rearrangement was found. At least one additional atypia was identified in 6/12 patients. Interestingly, ALCL patients had proportionally more recurrences than any other histological category, but without a corresponding increase in mortality. Among DLBCL group we found the highest rate of hyperdiploidy (22.2%). Only two (non-hyperdiploid) patients with BCL6 gene rearrangement were found. The single patient who relapsed had an IGL gene rearrangement, suggesting activation of an oncogene in the context of reciprocal chromosomal translocation involving the 22q11 region. No MYC or BCL2 gene rearrangements were found among DLBCL cases. In hyperdiploid patients, overrepresentation of chromosome 8 was found, along with overrepresentation of chromosome 3 (and, in addition, 18 in one of the two cases). This combination of atypias apparently leads to supernumerary copies of MYC gene, simultaneously with the presence of supernumerary alleles of BCL6 (or BCL2, respectively). Regarding findings in FL, MZL and PTLD, due to the small number of patients in these subgroups, any observation is of limited value. Absence of BCL2 gene rearrangement in childhood FL was confirmed. In the study's only patient with MZL, the identification of trisomy 3 may not be accidental, since this atypia is common in the corresponding adult disease. Of particular interest is the one patient with PTLD. Although monomorphic Burkitt-type PTLD was diagnosed and B-clonality documented based on VDJ recombination of IGH gene, marrow karyotyping and thorough i-FISH screening revealed no chromosomal atypia. The phenomenon has been highlighted in the literature and indicates that PTLD's aggressive clinical course is not necessarily associated with genomic instability and damage. In our study no patient met double-hit lymphoma criteria. We might wonder whether, in our series, the hyperdiploid patients with supernumerary copies of intact MYC, BCL2 and/or BCL6 genes constitute a subgroup of the "alternative" double hit lymphomas. With a median follow-up time of 61.5 months (range 7-123 months), 20 patients succumbed, yielding: 3-year and 5-year progression free survival (PFS) in all patients 84.5% και 82.5% respectively, and 3-year and 5-year OS in all patients 86.7%. Conclusions: This extensive i-FISH investigation provides clinically meaningful information on the genetic profile of NHLs, raises new questions, and points to directions for further investigation within the field of childhood lymphoproliferation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pediatrics Non-Hodgkin's Lymphoma Survivors: Should We Worry about Quality of Life and Late Therapy Effects?

Background: The survival outcomes of mature B-cell non-Hodgkin lymphoma (NHL) patients have improved due to advances in treatment. Objectives: In this study, we aim to assess the frequency and trends of the late effects and their impact on the quality of life among these survivors at Children Cancer Hospital Egypt. Design and methods: A retrospective study including all patients diagnosed with Non-Hodgkin's lymphoma "Mature B" at CCHE 57357 in the period between January 2012 till December 2015. All of the patients were examined clinically and assessed for: Cognitive functions (by assessing IQ level using (Stanford-Binet Intelligence Scales, Fifth Edition ''SB5''), Cardiac function, Endocrine function (Thyroid functions, Growth curves), Pulmonary function (pulmonary function test), Lipid profile (triglyceride, cholesterol, HDL, LDL) and Quality of life assessment (PedsQL). Results: A total of 345 patients were diagnosed of having mature B cell lymphoma during the study period. 213 were evaluable with a male: female ratio 4:1. Staging: stage I (7.5%), II (14.1%), III (58.7%), IV (19.7%). patients < 5 years of age tend to have more affection than those > 5 years. The total mean QoL score 99 ± 0.058, the order of the affected domains, according to severity: physical functioning 92 ± 0.1, emotional functioning 92 ± 0.15, followed by social functioning 97 ± 0.08, school functioning 99 ± 0.06. IQ scores (low average 24.4%, high average 10.3%, average 63.8%). Pulmonary functions test was evaluated in 123 patients with affection detected in (57.7%) as follows: (mild degree 34.2%, moderate 14%, severe 9.3%). Cardiac reported with early onset 22% (from which 63% resolved, 36% persistent), late-onset 10.3%. Lipid profile was significantly affected, showing dyslipidemia 61.9% (high triglycerides 21.6%, low HDL 16%, high LDL 8.9%, and high total cholesterol 41.8%) while Growth affection: regarding weight (25.4% dropped 2 or more centiles, height (33.3% dropped 2 or more centiles). Conclusion: long term NHL survivors, pulmonary and cardiac functions should be followed up for possible affection. Lipid profiles and weight affection should be monitored closely. A survivorship program for NHL in children is recommended. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

LABORATORY AND CLINICAL FEATURES OF TUMOR LYSIS SYNDROME IN CHILDREN WITH HIGH-GRADE NON-HODGKIN LYMPHOMA AND EVALUATION LONG-TERM RENAL FUNCTIONS IN SURVIVORS

Tumor lysis syndrome (TLS) describes biochemical and clinical abnormalities resulting from spontaneous or treatment-induced necrosis of rapidly proliferating tumors such as Burkitt's lymphoma (BL). TLS can lead to complications like acute kidney injury (AKI) which can be fatal. In patients who had AKI in childhood, the frequency of kidney problems increases in later ages. Therefore, there is a need to examine long term kidney functions in patients with TLS. The purpose of our study is to investigate the laboratory and clinical features of tumor lysis syndrome in childhood non-Hodgkin lymphomas (NHL) and to reveal its impact on long term kidney function in survivors. Our study was a single center retrospective study. 107 patients (0-18 years of age) admitted to our hospital between 1998-2020 years with a diagnosis of NHL and who received chemotherapy were included in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis and within 14 days from the start of chemotherapy were examined. The presence of TLS and its laboratory and clinical features were examined according to the Cairo-Bishop criteria. The relationship between TLS and age, gender, histopathological subgroup, tumor stage, lactate dehydrogenase (LDH) level at presentation, bone marrow and kidney involvement were investigated. The presence of AKI was determined according to the Kidney Disease: Improving Global outcomes criteria. Long-term renal functions of the patients were investigated. 80.3% of the patients with a median age of 9.8 years were male. The most common histopathological subgroup was BL (77.5%), while the majority of patients (76.7%) had advanced disease. Clinical TLS (CTLS) was observed in 12.1% of the cases, and isolated laboratory TLS (LTLS) was observed in 18.7%. Hyperhydration±alkalinization and allopurinol were used in first-line treatment and prophylaxis. A significant correlation was found between young age, advanced stage, high lactate dehydrogenase level at presentation and LTLS. Bone marrow involvement was found to be significantly higher in the group with CTLS. AKI was observed in 12.1% of the patients. Out of a total of 103 patients whose treatment was completed, 93 (90.3%) patients survived and 10 deaths were observed. No death due to TLS was observed. The mean survival time was 215.55±7.502 months. After an average of 6.9 years, when the glomerular filtration rate values of the patients at the first admission and at the last admission were compared, a mean decrease of 10 mL/min/1.73 m2 was detected. However, it was not found to be statistically significant. In our study, lower age, advanced stage, high LDH level at presentation were found to be risk factors for TLS. Long-term renal function loss was not detected in the survivors, for whom early and careful prophylaxis/treatment approaches were applied for TLS. The survivors are still being followed up.

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

To analyse the disease presentation, clinical course and long-term outcomes of children diagnosed with B-cell non-Hodgkin lymphoma. 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. 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%. Majority of the paediatric patients presented with extensive disease. Measures are needed for early recognition, identification, and prompt referral to paediatric cancer institute.

Clinico-pathological Profile of Childhood Nonhodgkin Lymphoma (NHL) in A Tertiary Care Hospital in Bangladesh

Background: Non-Hodgkin Lymphoma (NHL) is the third most common childhood malignancy. With histopathology based intensive chemotherapy and CNS-directed therapy, survival can reach more than 80%.&#x0D; Objective: The study was conducted to observe the clinico-pathological findings of NHL in Bangladeshi children.&#x0D; Methods: A prospective observational study was conducted in the Paediatric Haematology and Oncology Department of BSMMU from June 2012 to December 2012. Newly diagnosed NHL patients were included in the study. Patient’s initial clinical presentations, time interval from onset of symptoms to diagnosis were recorded. Diagnostic and staging workups were done by CBC, biochemistry, radio-imaging, histopathology (FNAC/excision biopsy), serous fluids/CSF cytology (cytospin), and bone marrow aspiration.&#x0D; Result: Among the 34 patients, BL had preponderance (n=23, 68%) then LL. Median age was 7.6 years. Male: female ratio was 2.1:1. Delayed diagnosis was found in 59% patient. Primary sites were abdomen (65%), thorax (32%), and head-neck (3%). At initial presentation, 83% patients of Burkitt NHL and 100% Lymphoblastic NHL patients came with advanced disease. Bone marrow involvement was found in 23.6% patients and 12% had CNS involvement at their presentation. Irrespective to histology, most common stage was stage-III, which was 53% and then stage-IV was 35%. Median LDH was 1719 U/L. Patient with abdominal variety of NHL came with abdominal complaint like pain (66%), distension (65%), ascites (48%), mass like hepatomegaly (39%), splenomegaly (26%), intussusceptions (8%), testicular involvement (4%). B symptoms were commonly found in 74% patient. Pallor (82%), anorexia, nausea &amp; vomiting (48%), oedema (25%), peripheral lymphadenopathy (49%) were also noticed. In case of thoracic variety of NHL, most common presentation was respiratory distress (90%), superior mediastinal syndrome (SMS) (45%), with high incidence of B symptoms (90%), peripheral lymphadenopathy (72%) with other respiratory finding like chest bulging, mediastinal mass, pleural effusion was also found.&#x0D; Conclusions: About 59% childhood NHL patients tend to present with delayed diagnosis and 88% with advanced disease. Burkitt NHL is the commonest childhood lymphoma, mostly presented with abdominal complaint. Thoracic variety is mostly Lymphoblastic lymphoma. Histopathological findings following excisional biopsy is the most significant and confirmatory for diagnosis. Serum LDH were found significantly high level in both varieties.&#x0D; DS (Child) H J 2021; 37(1): 21-27

High treatment related mortality due to infection remains a major challenge in the management of high-grade B-cell Non-Hodgkin Lymphoma in children in developing countries: Experience from a tertiary cancer center in Eastern India

BackgroundThough the outcome of high-grade B-cell Non-Hodgkin Lymphoma (B-NHL) has improved significantly in recent years, but the treatment related toxicity is still high. ObjectivesTo study the demographic characteristics, outcome, and toxicity of FAB/LMB 96 backbone in pediatric patients with B-NHL. Materials and methodsA retrospective single center review of records of all patients <18 years of age with B-NHL treated on FAB/LMB 96 protocol at a tertiary cancer center between January 2011 to January 2020. ResultsOut of the total 47 patients, there were 44 males and 3 females. Median age of presentation was 8 years 9 months. Total patients allocated to group A, B and C were 3 (6.4%), 29 (61.7%), and 15 (31.9%) respectively. With median follow up of 20 months, 2-year overall survival (OS) and event-free survival (EFS) for the whole cohort was 73.4% and 72.8%, respectively. The 2-year OS and EFS for group A, B and C were 100%, 82.6%, 45.7% and 100%, 81.9%, 45.0% respectively. There were total 13 deaths out of which 8 (61.5%) were treatment related mortality (TRM). Almost all of the TRM (7/8; 83.3%) were due to multi-drug resistant organism (MDRO) sepsis. ConclusionsThis study shows outcomes comparable to other centers in low and intermediate risk patients. Children with high-risk disease however have poor outcome due to high MDRO sepsis related mortality, a finding consistently shared across other centers in resource limited settings. This emphasizes on the need for newer strategies in this group of patients probably as an InPOG prospective multicenter trial including immunotherapy and chemotherapy backbone according to local practicalities. In contrast to the recently published Indian study, we did not find excess toxic deaths in our cohort of patients receiving rituximab.