Childhood non-Hodgkin Lymphoma Research Articles

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.

MINIMAL DISSEMINATED AND MINIMAL RESIDUAL DISEASE IN CHILDHOOD AND ADOLESCENT NON‐HODGKIN LYMPHOMA

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.

Clinical characteristics and treatment outcomes of children and adolescents with aggressive mature B-cell lymphoma: a single-center analysis

BackgroundAggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is the most common non-Hodgkin lymphoma in children. The outcome of chemotherapy for B-NHL has improved over decades.MethodsWe reviewed 82 children and adolescents with B-NHL diagnosed at Asan Medical Center between 1993 and 2020. The D-COMP/COMP (daunomycin–cyclophosphamide, doxorubicin, vincristine, and prednisolone), Pediatric Oncology Group (POG)-9219/9315/9317, R-CHOP/CHOP (rituximab–cyclophosphamide, doxorubicin, vincristine, and prednisolone), and Lymphomes Malins B 89 (LMB89)/LMB96 regimens were administered. In 2018, rituximab was added to the LMB protocol (R-LMB) for advanced-staged Burkitt lymphoma (BL). The patients’ clinical features and treatment outcomes were retrospectively analyzed.ResultsThe most common subtype was BL (61%), followed by diffuse large B-cell lymphoma (DLBCL) (35%). The median age was 7.8 (range, 1.3‒16.4) years, and the most frequently used regimen was French‒American‒British (FAB)/LMB96 (58 patients, 70.7%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 92.5% and 85.7%, respectively. The EFS rates of patients with BL and DLBCL were 90.0% and 79.3%, respectively. Among the FAB/LMB risk groups, group C (85.7%) had a significantly lower 5-year OS (P=0.037). Eleven events occurred (6 relapses, 3 deaths, and 2 secondary malignancies) during the median follow-up of 7.1 (range, 3.7‒118.5) months. Two patients treated with R-LMB had good outcomes without complications.ConclusionVarious treatment regimens have favorable outcomes in pediatric patients with B-NHL. However, further studies are needed to improve survival in high-risk patients. In addition, careful monitoring for acute toxicity or secondary malignancy due to intensive multidrug chemotherapy is required.

The New Treatment Methods for Non-Hodgkin Lymphoma in Pediatric Patients.

Simple SummaryNon-Hodgkin lymphoma is one of the most frequently occurring hematologic diseases in the world. Current drugs and therapies have improved outcomes for patients with lymphoma, but there is still a need to identify novel medications for treatment-resistant cases. The aim of this review is to gather the latest findings on non-Hodgkin lymphoma in children, including genetic approaches, the application of therapy, the available treatment options, and resistance to medications.One of the most common cancer malignancies is non-Hodgkin lymphoma, whose incidence is nearly 3% of all 36 cancers combined. It is the fourth highest cancer occurrence in children and accounts for 7% of cancers in patients under 20 years of age. Today, the survivability of individuals diagnosed with non-Hodgkin lymphoma varies by about 70%. Chemotherapy, radiation, stem cell transplantation, and immunotherapy have been the main methods of treatment, which have improved outcomes for many oncological patients. However, there is still the need for creation of novel medications for those who are treatment resistant. Additionally, more effective drugs are necessary. This review gathers the latest findings on non-Hodgkin lymphoma treatment options for pediatric patients. Attention will be focused on the most prominent therapies such as monoclonal antibodies, antibody–drug conjugates, chimeric antigen receptor T cell therapy and others.

Progress against non-Hodgkin's lymphoma in children and young adolescents in the Netherlands since 1990: Stable incidence, improved survival and lower mortality

BackgroundWith epidemiologic analyses of population-based trends in incidence and outcomes, we ascertained progress against non-Hodgkin's lymphoma (NHL) in children and young adolescents in the Netherlands since 1990. MethodsTumour characteristics were extracted from the Netherlands Cancer Registry for patients aged <18 years at diagnosis, between 1990 and 2015. Mortality data for 1980–2016 were derived from Statistics Netherlands. NHL subtypes comprised lymphoblastic lymphoma (LBL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL). Time trends in incidence and mortality rates and 5-year overall survival (OS) rates were evaluated by average annual percentage change (AAPC) analyses and parametric survival models, respectively. ResultsOverall incidence of NHL remained stable at 11 per million person-years (AAPC -0.2%, p = 0.68), with a marked decrease among children of 5–9 years (AAPC -2.6%, p < 0.01), especially among those with BL. Treatment regimens comprised less radiotherapy over time, especially for LBL and BL. Since 2004, most 15–17-year-old patients with NHL have been treated at a paediatric oncology centre. Five-year OS improved from 71% in 1990–94 to 87% in 2010–15 (p < 0.01), the most gain has been achieved in patients with DLBCL and ALCL from 60% and 73%, respectively, to both 90%. Population-based mortality from NHL decreased significantly towards 1.4 per million person-years (AAPC -4.2%, p < 0.01). ConclusionsThis population-based epidemiological study exhibited significant progress against childhood and young adolescent NHL in the Netherlands since 1990, before the advent of a national paediatric oncologic centre in 2018: incidence decreased among children of 5–9 years, survival improved, and mortality steadily decreased over time.

Protocol and immunohistochemistry-based diagnosis and treatment of Non-Hodgkin lymphoma in children: Experience over two decades from a tertiary referral centre in South India

Protocol and immunohistochemistry-based diagnosis and treatment of Non-Hodgkin lymphoma in children: Experience over two decades from a tertiary referral centre in South India

Patient parameters and response after administration of rituximab in pediatric mature B-cell non-Hodgkin lymphoma.

Mature aggressive B-cell lymphomas are heterogenous malignancies that make up more than half of all diagnosed non-Hodgkin lymphoma in children and adolescents. The overall survival rate increased over the last decades to 80%-90% due to fine tuning of polychemotherapy. However, new therapeutic implications are needed to further increase the overall survival. Current clinical trials analyze the therapeutic effect of rituximab in pediatric patients, while the mechanism of action in vivo is still not fully understood. Effector molecules important for tumor defense were analyzed before and at day 5 after rituximab treatment via flow cytometry. Serum rituximab levels were measured with an ELISA. We evaluated patient parameters that may affect treatment response in relation to rituximab administration and serum rituximab levels. We indeed found a reduction of Fcγ receptor (FcγR) II levels after rituximab treatment in monocyte subtypes, whereas FcγRI expression was significantly increased. Serum levels of proinflammatory marker proteins S100A8/A9 and S100A12 significantly decreased after treatment to normal levels from an overall proinflammatory state before treatment. CD57, perforin, and granzyme B expression decreased after treatment, comprising a less cytolytic natural killer (NK) cell population. The highlighted effects of rituximab treatment on patient's immune response help in understanding the biology behind tumor defense mechanisms and effector function. After subsequent studies, these novel insights might be translated into patient care and could contribute to improve treatment of pediatric patients with mature aggressive B-cell lymphoma.

Ruxolitinib as a Novel Therapeutic Option for Poor Prognosis T-LBL Pediatric Patients.

Simple SummaryCurrent treatment protocols for pediatric patients with T-Lymphoblastic lymphoma (T-LBL) allow the achievement of a complete remission in around 85% of T-LBL pediatric patients; however the overall survival rate of second-line treatments for patients with progressive disease or relapse is around 14%. Thus, the major issues to be addressed are the identification of a valuable predictor marker to foresee the disease risk and new therapeutic targets to improve relapsed/resistant patients’ outcome. We identified JAK2 Y1007-1008 as a potential prognosis marker as well as a therapeutic target for patients with progressive disease or relapse and suggest that its inhibition by ruxolitinib, a JAK1/2 FDA approved inhibitor, could represent a novel therapeutic approach to overcome therapy resistance and meliorate the outcome of pediatric T-LBL patients.Lymphoblastic lymphoma (LBL) is the second most common type of non-Hodgkin lymphoma in childhood, mainly of T cell origin (T-LBL). Although current treatment protocols allow a complete remission in 85% of cases, the second-line treatment overall survival for patients with progressive or relapsed disease is around 14%, making this the major issue to be confronted. Thus, we performed a Reverse Phase Protein Array study in a cohort of 22 T-LBL patients to find reliable disease risk marker(s) and new therapeutic targets to improve pediatric T-LBL patients’ outcome. Interestingly, we pinpointed JAK2 Y1007-1008 as a potential prognosis marker as well as a therapeutic target in poor prognosis patients. Hence, the hyperactivation of the JAK1/2-STAT6 pathway characterizes these latter patients. Moreover, we functionally demonstrated that STAT6 hyperactivation contributes to therapy resistance by binding the glucocorticoid receptor, thus inhibiting its transcriptional activity. This was further confirmed by specific STAT6 gene silencing followed by dexamethasone treatment. Finally, JAK1/2-STAT6 pathway inhibition by ruxolitinib, an FDA approved drug, in cell line models and in one T-LBL primary sample led to cell proliferation reduction and increased apoptosis. Globally, our results identify a new potential prognostic marker and suggest a novel therapeutic approach to overcome therapy resistance in pediatric T-LBL patients.