Incidence Of Burkitt's Lymphoma Research Articles

Mosquito Bed Net Use and Burkitt Lymphoma Incidence in Sub-Saharan Africa

Burkitt lymphoma (BL) is one of the most common childhood cancers in sub-Saharan Africa and is etiologically linked to malaria. However, evidence for an effect of malaria interventions on BL is limited. To investigate the potential population-level association between large-scale rollout of insecticide-treated bed nets (ITNs) in sub-Saharan Africa in the 2000s and BL incidence. In this systematic review and meta-analysis, a search was conducted in the Embase, Global Health, and Medline databases and in cancer registry publications between January 1, 1990, and February 27, 2023. All epidemiologic studies on BL incidence rates in children and adolescents aged 0 to 15 years in sub-Saharan African countries where malaria is endemic were identified by 2 reviewers blinded to each other's decision. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Data were extracted independently by 2 reviewers, and quality was scored based on 3 predefined criteria: data collection, case ascertainment, and calculation of person-time at risk. Incidence rates of BL during childhood and mean ITN use in the population. Data were analyzed using a random-effects negative binomial regression model. Of 2333 studies meeting selection criteria, 23 comprising 66 data points on BL incidence were included based on 5226 BL cases from locations with large-scale ITN use in 17 countries. Rates of BL were 44% (95% CI, 12%-64%) lower in the period after ITN introduction compared with before. The adjusted pooled incidence rates of BL were 1.36 (95% CI, 0.88-2.10) and 0.76 (95% CI, 0.50-1.16) per 100 000 person-years before and after introduction of ITNs, respectively. After adjusting for potential confounders, a 1-percentage point increase in mean ITN use in the population in the 10 years before BL data collection was associated with a 2% (95% CI, 1%-4%) reduction in BL incidence. In this systematic review and meta-analysis, large-scale rollout of ITNs in the 2000s was associated with a reduction in BL burden among children in sub-Saharan Africa. Although published data may not be representative of all incidence rates across sub-Saharan Africa, this study highlights a potential additional benefit of malaria control programs.

Use of Insecticide-Treated Bed Nets and Incidence of Burkitt Lymphoma

Use of Insecticide-Treated Bed Nets and Incidence of Burkitt Lymphoma

Incidence of Burkitt lymphoma in the United States during 2000 to 2019.

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that occurs worldwide. A study of BL in the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program during 1973 to 2005 (n = 3043) revealed three age-specific incidence peaks of BL and rates that were rising. We studied BL cases diagnosed in SEER 22 during 2000 to 2019 (n = 11 626) to investigate age-specific BL incidence rates and temporal trends. The age-standardized BL incidence rate was 3.96/million person-years, with a 2.85:1 male-to-female ratio. The BL rate among both Hispanic and White individuals was higher than in Black individuals (4.52, 4.12 vs 3.14). Age-specific BL rates showed peaks during pediatric, adult and elderly years in males and pediatric and elderly peaks in females. Based on 4524 BL cases with HIV status (SEER 13), only one peak in adult males (45 years) was observed. Overall age-standardized BL incidence rates rose 1.2%/year (not significant) up to 2009 then fell significantly by 2.4%/year thereafter. Temporal trends in BL rates during 2000 to 2019 varied with age group as pediatric BL rates rose 1.1%/year, while elderly BL rates fell 1.7%/year and adult BL rates rose 3.4%/year until 2007 before falling 3.1%/year thereafter. Overall survival from BL was 64% at 2 years, being highest in pediatric patients and lowest in Black and elderly individuals vs other subgroups. Survival improved by 20% between 2000 and 2019. Our data suggest that BL age-specific incidence rates are multimodal and that overall BL rates rose up to 2009 and then fell, suggesting changes in etiological factors or diagnosis.

Spatial distribution of incident pediatric Burkitt lymphoma in central and northern Malawi and association with malaria prevalence.

Burkitt lymphoma (BL) accounts for 90% of pediatric lymphomas in sub-Saharan Africa. Plasmodium falciparum malaria is considered an etiological factor of BL. We describe the geographic distribution of pediatric BL in Malawi and association with P. falciparum malaria prevalence rate (PfPR). We enrolled 220 pathologically confirmed incident pediatric BL cases (2013-2018) into an observational clinical cohort at Kamuzu Central Hospital (KCH) in Lilongwe district. KCH is the main tertiary cancer referral center serving the central and northern regions of Malawi. Using an ecological study design, we calculated district-level annual BL incidence rate using census population estimates. District-level PfPR was extracted from the National Malaria Control Program 2010 report. BL incidence and PfPR maps were constructed in QGIS. Moran's I test was used to identify BL spatial clusters. Pearson's correlation and multiple linear regression analyses were used to statistically examine the relationship between PfPR and BL. BL incidence was higher in central region districts (8.2 cases per million) than northern districts (2.9 cases per million) and was elevated in lakeshore districts. Districts with elevated PfPR tended to have elevated BL incidence. A low-risk BL cluster was detected in the north. Statistically, BL incidence was positively correlated with PfPR (r=.77, p<.01). A 1% increase in PfPR predicted an increase in BL incidence of 0.2 cases per million (p=.03), when controlling for travel time from referral district hospital to KCH. Our study supports evidence for an association between P. falciparum and BL and highlights a need to improve geographic accessibility to tertiary cancer services in Malawi's northern region.

Burkitt Lymphoma Incidence in Five Continents

Burkitt lymphoma (BL) is a rare non-Hodgkin lymphoma first described in 1958 by Denis Burkitt in African children. BL occurs as three types, endemic, which occurs in Africa and is causally attributed to Epstein-Barr virus and P. falciparum infections; sporadic, which occurs in temperate areas, but the cause is obscure; and immunodeficiency-type, which is associated with immunosuppression. All BL cases carry IG∷MYC chromosomal translocations, which are necessary but insufficient to cause BL. We report a comprehensive study of the geographic, sex, and age-specific patterns of BL among 15,122 cases from Cancer Incidence in Five Continents Volume XI for 2008–2012 and the African Cancer Registry Network for 2018. Age-standardized BL rates were high (&gt;4 cases per million people) in Uganda in Africa, and Switzerland and Estonia in Europe. Rates were intermediate (2–3.9) in the remaining countries in Europe, North America, and Oceania, and low (&lt;2) in Asia. Rates in India were 1/20th those in Uganda. BL rates varied within and between regions, without showing a threshold to define BL as endemic or sporadic. BL rates were twice as high among males as females and showed a bimodal age pattern with pediatric and elderly peaks in all regions. Multi-regional transdisciplinary research is needed to elucidate the epidemiological patterns of BL.

Spatial Distribution of Incident Pediatric Burkitt Lymphoma in Central and Northern Malawi and Association With Malaria Prevalence

PURPOSE Burkitt lymphoma (BL) accounts for 90% of pediatric lymphomas in sub-Saharan Africa. Plasmodium falciparum (Pf) malaria is considered an etiological factor of BL. We describe the geographic distribution of pediatric BL in Malawi and association with malaria prevalence (PfPR). We also examine the influence of travel time to cancer referral center as a potential confounder. METHODS We enrolled pathologically confirmed incident pediatric BL cases (2013-2018) into a prospective observational cohort at Kamuzu Central Hospital (KCH) in Lilongwe, the main tertiary cancer referral center serving central and northern Malawi. District of residence was recorded for all participants. We calculated district-level average annual BL incidence rate (BLIR) using census population estimates. PfPR was extracted from the National Malaria Control Program 2010 report. BLIR and PfPR maps were constructed in QGIS. Moran's I was used to identify BL spatial clusters. Travel time to KCH was modeled in AccessMod. Pearson's correlation and multivariate regression was used to statistically examine the relationship between PfPR, travel time to KCH and BL. RESULTS Of 220 participants, 69 (31%) resided in Lilongwe. BLIR was higher in central region districts (0.86 cases per 100,000) than northern districts (0.32 cases per 100,000). BLIR was elevated in lakeshore districts. Districts with elevated PfPR tended to have elevated BLIR. A low-risk BL cluster was detected in the northern region. BLIR was lower in districts where travel time to KCH exceeded 4 hours, particularly the north. Statistically, BLIR was positively correlated with PfPR ( r = 0.77, P &lt; .01) and negatively correlated with travel time to KCH ( r = –0.67, P &lt; .01). A 1% increase in PfPR predicted an increase in BLIR of 0.02 cases per 100,000 ( P = .03) when controlling for travel time to KCH. CONCLUSION Our study supports evidence for an association between Pf and BL. Additionally, our results may indicate a need to improve geographic accessibility to tertiary cancer services in Malawi's northern region.

Trends in pediatric lymphoma incidence by global region, age and sex from 1988-2012

BackgroundGlobal variation in lymphoma incidence by type and age at diagnosis, region, sex, and Human Development Index (HDI) categories has not been reported, may shed light on potential biologic mechanisms and identify areas for targeted interventions. MethodsUsing the Cancer Incidence in Five Continents data from 1988 to 2012, we identified Hodgkin (HL), non-Hodgkin (NHL), and Burkitt lymphoma (BL) diagnosed in children aged 0–19 years. We estimated incidence rates (IRs; cases/million) and average annual percent change in incidence (AAPC; 95 % CI) by geographic region, sex, and HDI for each age group (0−9years and 10−19 years). ResultsThere were 42,440 NHL, 38,683 H L, and 7703 included. Southern European (SE) 10−19-year-olds (yo) had the highest IR of NHL (19.6 cases/million) in 2008−2012. HL IRs for 0−9yo were <6 cases/million and >25 cases/million for 10−19yo in European regions and Oceania (OC). BL IRs were generally <5cases/million. Northern Europe (NE), SE, and OC 10−19yo had significantly increased APPCs in incidence for all lymphomas with the largest increases in BL (NE AAPC: 7.69 %; 95 % CI: 5.27, 10.16; SE AAPC: 5.21 %; 95 % CI: 3.26, 7.19; OC AAPC: 3.97 %; 95 % CI: 3.26, 4.70). BL incidence increased among males of all ages by approximately 2 %. NHL and BL incidence increased significantly among 10−19yo in very high HDI countries by approximately 3 %. ConclusionsSouthern and Northern Europe and Oceania displayed increased incidence of all lymphomas studied from 1988 to 2012. BL incidence significantly increased in 8 of 15 global regions, males, and higher HDI countries over the study period. Mechanisms underlying these increases remain to be elucidated.

HIV Nef enhances the expression of oncogenic c-MYC and activation-induced cytidine deaminase in Burkitt lymphoma cells, promoting genomic instability

BackgroundNon-Hodgkin lymphoma is of high prevalence among HIV-infected people. In particular, the incidence of HIV-associated Burkitt lymphoma (BL) remains high despite the advent of Highly Active Anti-Retroviral Therapy. Recent evidence shows that serum-soluble HIV proteins can enhance oncogenesis, particularly in lymphoid tissues. This study sought to define the role of HIV protein Negative regulatory factor (Nef) in BL development by assessing its effect on key lymphoma driver genes.MethodsA recombinant Nef protein was used to assess changes in expressions of activation-induced cytidine deaminase (AICDA/AID) and c-MYC in B lymphocytes exposed extracellularly to the protein. Additionally, changes in the promoter activities of these genes were measured using a Nef-expressing cellular model and reporter assays. Confocal microscopy was used to observe c-MYC and AID expression and localization, and genomic integrity via the recruitment of phosphorylated γ-H2AX, in Nef-exposed cells.ResultsmRNA transcription of c-MYC and AICDA were significantly enhanced in lymphoma cells, up to 2-fold for c-MYC and up to 4-fold for AICDA, when exposed to varying concentrations of Nef (0–1000 ng/ml) and for different periods of time (3, 6 and 12 h). The protein expressions of AID and c-MYC followed a similar pattern and these effects were specific to BL but not lymphoblastoid cells. While the promoter activity of c-MYC was enhanced in the presence of Nef in a dose-dependent manner, the same was not observed for AICDA. Both AID and c-MYC accumulated within the cytoplasmic and nuclear spaces of Nef-exposed lymphoma cells, with a concomitant increase in DNA double strand breaks within the genome.ConclusionsExposure to HIV Nef leads to significant increases in AID and c-MYC, leading to genomic instability, potentially enhancing the oncogenic potential of Burkitt lymphoma. Our findings align with that of others to show that HIV proteins can directly contribute to the development and pathogenesis of HIV-associated lymphoma and accounts for the elevated incidence of BL observed in the HIV-infected population.

Global and regional incidence, mortality and disability-adjusted life-years for Epstein-Barr virus-attributable malignancies, 1990-2017.

ObjectiveTo determine the global and regional burden of Epstein-Barr virus (EBV)-attributed malignancies.DesignAn international comparative study based on the Global Burden of Disease (GBD) Study estimates.SettingGlobal population by age, sex, region, demographic index and time.Methods and outcome measuresThe burden of EBV-attributed Burkitt lymphoma (BL), Hodgkin lymphoma (HL), nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC) was estimated in a two-step process. In the first step, the fraction of each malignancy attributable to EBV was estimated based on published studies; this was then applied to the GBD estimates to determine the global and regional incidence, mortality and disability-adjusted life-years (DALYs) for each malignancy by age, sex, geographical region and social demographic index (SDI) from 1990 to 2017.ResultsThe combined global incidence of BL, HL, NPC and GC in 2017 was 1.442 million cases, with over 973 000 deaths. An estimated 265 000 (18%) incident cases and 164 000 (17%) deaths were due to the EBV-attributed fraction. This is an increase of 36% in incidence and 19% in mortality from 1990. In 2017, EBV-attributed malignancies caused 4.604 million DALYs, of which 82% was due to NPC and GC alone. The incidence of both of these malignancies was higher in high and middle-high SDI regions and peaked in adults aged between 50 and 70 years. All four malignancies were more common in males and the highest burden was observed in East Asia.ConclusionsThis study provides comprehensive estimates of the burden of EBV-attributed BL, HL, NPC and GC. The overall burden of EBV-related malignancies is likely to be higher since EBV is aetiologically linked to several other malignancies not included in this analysis. Increasing global population and life expectancy is expected to further raise this burden in the future. The urgency for developing an effective vaccine to prevent these malignancies cannot be overstated.

Stable Incidence and Poor Survival for HIV-Related Burkitt Lymphoma Among the US Veteran Population During the Antiretroviral Era.

Despite advances in diagnosis and treatment of both HIV and Burkitt lymphoma (BL), persons living with HIV remain at high risk for BL. We conducted this study to evaluate if there have been any changes in the risk of or survival after BL diagnosis among persons living with HIV during the antiretroviral era. Veterans living with HIV (VLWH) and age-matched HIV-negative controls receiving care between 1999 and 2016 were retrospectively identified using Veterans Health Administration electronic medical records. We identified BL diagnoses through Veterans Health Administration Cancer Registry review and International Classification of Diseases, Ninth/Tenth Revisions, codes, and we extracted demographic, lifestyle, and clinical variables from electronic medical record. We estimated hazard ratios (HR) and 95% confidence intervals (CIs) for BL risk and survival using Cox proportional models. We identified 45,299 VLWH. Eighty-four developed BL (incidence rate = 21.2 per 100,000 person years; CI: 17.1 to 26.3). Median CD4 count at BL diagnosis was 238 cells per milliliter (SD: 324.74) and increased over time. Survival was truncated in VLWH with BL (P < 0.05). The risk of BL in VLWH was 38% less in blacks compared with whites (HR: 0.620; CI: 0.393 to 0.979; P = 0.0401). VLWH with an undetectable viral load for at least 40% of follow-up were 74% less likely to develop BL (HR: 0.261; CI: 0.143 to 0.478; P < 0.0001) and 86% less likely to die after diagnosis (HR: 0.141; CI: 0.058 to 0.348; P < 0.0001). BL incidence among VLWH did not improve between 2000 and 2016. Survival after BL diagnosis in VLWH remains dismal as compared with their HIV-negative counterparts, although veterans with prolonged periods of undetectable viral load had improved prognosis.

Status and prognostic nomogram of patients with Burkitt lymphoma.

The purpose of the present study was to evaluate the newest status of patients diagnosed Burkitt lymphoma (BL), an aggressive lymphoma subset with a high cure rate. Furthermore, the study aimed to create prognostic nomograms to consider various prognostic factors and estimate patient survival, paving the way for clinical decision-making. A total of 4,600 patients diagnosed with BL between 1983 and 2015 were investigated, via data collected from the SEER database. The overall status of the patients was analyzed through several aspects, including incidence and survival analysis of the previous three decades using the log-rank test and the Kaplan-Meier method. In order to construct and validate the nomograms, the patient diagnosed during 2005–2015 were randomly assigned to the training cohort and validation cohort. Univariate and multivariate analyses were applied to identify independent factors that were further included in the nomograms, predicting 3- and 5-year overall survival (OS) and cancer-specific survival (CSS). The data of the training cohort were used for internal validation and validation cohort used to external validation. C-index and calibration plots were used to validate the nomograms, comparing predicted values with actual outcomes. The incidence of BL was gradually increased from 1984 and reached its peak in 2009, at a rate of 0.491 per 100,000 [95% confidence interval (CI), 0.412–0.581]. From 2009, the incidence slowly declined year by year and dropped to 0.280 per 100,000 (95% CI, 0.224–0.346). The OS and CSS rates of patients diagnosed between 2005 and 2015 were increased, in contrast with those of patients diagnosed from 1983–1993 and 1994–2004. A total of five variables, including age, race, chemotherapy, primary site and stage, proved to be the prognostic factors of BL and were used to construct the nomograms predicting 3- and 5-year OS and CSS. The internal and external calibration plots for the probability of 3- and 5-year OS and CSS were consistent between nomogram prediction and observed outcomes. The slow decline in incidence and the significantly improved cure rate make BL a disease that is no longer an urgent problem. Effective nomograms were developed to predict the OS and CSS of patients with BL.

Burkitt lymphoma: Trends in children below 15 years reveal priority areas for early diagnosis activities in north-west Cameroon

Background: Burkitt lymphoma is one of the most common childhood cancers in Cameroon. Incidence rates of 5.9/100 000 and 2.58 per 100 000 have been reported in two studies in 2005 and 2012 amongst children below 15 years in the North-West Region.Aim: This study seeks to examine how Burkitt lymphoma incidence has varied between the various health districts of north-west Cameroon from 2003 to 2015.Setting: North-West region of Cameroon.Method: Ethics approval was obtained from the relevant university and Health Services Institutional Review Board. Population data was obtained from the regional delegation of public health. The Paediatric Oncology Networked Database registry from two hospitals and two pathology-based registries were reviewed for cases per year from the various districts. Age-standardised incidence rates were computed for all districts by year using the World Health Organizaion world standard populations.Results: A total of 317 cases were registered. Overall age-standardised incidence rate was 3.07 per 100 000. Annual incidence ranged from 0.09 in 2003 to 6.12 in 2010. The districts with the highest incidence rates for the entire study period include Nwa with 10.54; Ndop with 5.63; Benakuma with 5.48; Ako with 4.97; and Nkambe with 4.73.Conclusion: Clustering of Burkitt lymphoma is seen in the region, with the highest incidence in Nwa, Ndop, Benakuma, Ako and Nkambe. These districts should be prioritised for awareness creation campaigns. There is need for a population-based childhood cancer registry in the region, which will use both active and passive surveillance methods to record all childhood cancer cases.

Clinical profile and outcomes of Non-Hodgkin's lymphoma in children: A report from a tertiary care hospital from India

Abstract Background: Non-Hodgkin's lymphoma (NHL) is an aggressive malignancy. Its outcome has improved over the past decades. Although it accounts for 8%–10% of all childhood cancers, very less information about its clinical presentation and outcomes is available from India. Our objective was to study the clinical presentation and outcomes in children (&lt;15 years) with NHL at our center. Methodology: We retrospectively analyzed 26 children diagnosed with NHL at our center from August 2008 to June 2014 and followed them up to May 2017. Results: The median age at the time of diagnosis was 7.7 years (2.5–13 years). Abdominal distension and an abdominal lump were the most common presenting features occurring in 75%, followed by fever (73.8%) and weight loss (46.2%). Most patients had advanced-stage (Stage III/IV, 92.3%) disease at presentation. The primary presentation was extranodal in 57.7%, nodal in 26.9%, and combined in 15.4%. Burkitt's lymphoma (BL) was the most common subtype (46.2%), followed by T-lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma. Three patients did not take treatment. The median follow-up of patients was 48 months (36–99 months). Nineteen patients achieved remission and four had progressive disease. Significantly better event-free survival (EFS) was found with younger age and lower stage of presentation. The EFS did not significantly differ with sex, group of disease, lactate dehydrogenase levels, and presenting features. Conclusions: Our cohort of patients with NHL showed characteristics similar to those reported from other developing countries. NHL occurred at a younger age, with a higher incidence of BL. The outcome for patients aged &gt;10 years was poor. The outcome of NHL was comparable to that of other centers in the world.

HIV Tat induces a prolonged MYC relocalization next to IGH in circulating B-cells.

With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners. The two partner genes, MYC and IGH, were found colocalized only very rarely in the nuclei of normal peripheral blood B-cells examined using 3D-FISH while circulating B-cells from HIV-infected individuals whose exhibited consistently elevated levels of MYC-IGH colocalization. In vitro, incubating normal B-cells from healthy donors with a transcriptionally active form of the HIV-encoded Tat protein rapidly activated transcription of the nuclease-encoding RAG1 gene. This created DNA damage, including in the MYC gene locus which then moved towards the center of the nucleus where it sustainably colocalized with IGH up to 10-fold more frequently than in controls. In vivo, this could be sufficient to account for the elevated risk of BL-specific chromosomal translocations which would occur following DNA double strand breaks triggered by AID in secondary lymph nodes at the final stage of immunoglobulin gene maturation. New therapeutic attitudes can be envisioned to prevent BL in this high risk group.

Comparative Analysis of Endemic and Sporadic Burkitt Lymphoma By RNA Sequencing

Introduction: Burkitt lymphoma (BL) is an aggressive B-lineage non-Hodgkin lymphoma that has traditionally been classified into 3 subtypes: "endemic", "sporadic", and HIV-associated. The highest incidence of BL - prompting the "endemic" classification - is observed in children in sub-Saharan Africa, where the distribution of the disease is closely associated with that of P. falciparum malaria. The tumor cells in most cases of BL from sub-Saharan Africa are infected with Epstein Barr virus (EBV). In contrast, a minority of BL tumors from Europe and North America - which are commonly described as "sporadic" - are EBV positive. Although excellent outcomes have been observed for patients with BL treated with multi-agent chemotherapy in Europe and North America, the outcomes of BL patients in sub-Saharan Africa are suboptimal. We hypothesized that improved understanding of the molecular heterogeneity that exists within BL, particularly the molecular features that distinguish cases from sub-Saharan Africa from those from Europe/North America, will enable more effective treatment strategies that can readily be implemented in low-resources settings.Methods: Tumor biopsies were collected from 19 pediatric patients who presented to the Uganda Cancer Institute with maxillofacial tumors histologically confirmed to be BL. Total RNA was extracted and polyA-selected sequencing libraries were prepared. Paired-end, 50-base pair sequencing was performed on the Illumina HiSeq 2500 platform at a depth of 100 million reads per sample. A publicly available RNA sequencing dataset from 28 BL cases from Europe and North America that were previously analyzed by both microarray (NEJM 2006; 354[23]: 2431-2442) and RNA sequencing (Nature 2012; 490[7418]: 116-120) was analyzed in parallel for comparison. RNA sequencing on the 28 sporadic BL tumors was performed on polyA-selected sequencing libraries with paired-end, 108-base pair sequence reads generated on the Illumina HiSeq 2000 platform. The reads from all 47 BL tumors were aligned to the human and EBV (GenBank ID KC207813.1) genomes using the STAR aligner. Tumors were deemed EBV positive if the ratio of mapped viral reads to human reads exceeded 0.001%, since the EBV genome is 0.005% the size of the human genome. Normalization and differential expression analysis were performed on aligned reads using the DESeq2 R package. Somatic variants were identified by the Genome Analysis Tool Kit. Analysis of alterative splicing was performed with the SGSeq R package.Results: All of the Uganda BL cases but only 70% of the previously published European/North American cases were obtained from children less than 18 years; 61% and 87% were from male patients, respectively. One half of patients in both groups presented with Ann Arbor stage I or II disease, while the remainder presented with higher stage disease. The median survival in the 19 Ugandan patients was less than one year. Sequence reads from 15 (79%) of the Ugandan tumors and 4 (15%) of the European/North American tumors aligned to the EBV genome. Although BL is reported to express only latency type I EBV genes, expression of latency type I, II, and III genes was detected. Among the 4 tumors from Uganda that did not contain EBV-derived reads, 1 was from a child who was HIV-seropositive, while the others were from HIV-seronegative patients. Unsupervised hierarchical clustering and principal component analysis of all annotated genes failed to separate EBV positive and EBV negative tumors. Cluster analysis of the Ugandan tumors revealed no association with clinical variables. Ongoing analyses are being performed to identify associations between differentially expressed genes and somatic mutations and alternative splicing that may distinguish the tumor subtypes.Conclusions: While the terms "endemic" and "sporadic" have traditionally been used to classify BL, this nomenclature is archaic and does not accurately capture the underlying biology of the tumor subtypes. We performed a comparative whole transcriptome analysis of BL tumors from patients in Uganda to a dataset of BL tumors from patients in Europe/North America to identify features that distinguish the two cohorts. While cluster analysis failed to clearly separate tumors by their EBV or clinical status, ongoing analyses are being performed to identify alterations that may contribute to their distinct gene expression profiles. DisclosuresNo relevant conflicts of interest to declare.

Treating Children With Cancer Worldwide--Challenges and Interventions.

* Abbreviations: ALL — : acute lymphoblastic leukemia HICs — : high-income countries LMICs — : low- and middle-income countries > Although morbidity from childhood cancer is second only to unintentional injuries in high-income countries, in low-income countries, it hardly hits the radar screen compared with death from pneumonia, diarrhea, malaria, neonatal sepsis, preterm birth, and neonatal asphyxia. Nevertheless, the extraordinary progress made in treating childhood cancer in high-income countries brings into harsh focus the mammoth disparities that exist in impoverished areas of the world. As the capacity to diagnose and treat childhood cancer improves in low- and middle-income countries, the ability to improve outcomes for the more common diseases benefits as well. The authors have summarized the issues related to childhood cancer care with thoughtful attention to how children everywhere can gain from the advances in medical science in high-income nations. > > Jay E. Berkelhamer > > Column Editor Childhood cancer is a relatively rare disease, and most cases occur in the low- and middle-income countries (LMICs) where nearly 90% of the world’s children live.1,2 In low-income countries, childhood cancer mortality is low compared with childhood mortality from other causes (eg, infectious disease). However, as mortality rates from other causes decreased by 49% worldwide from 1990 to 2013 for children aged under 5 years, so the relative importance of childhood cancer has increased.2,3 Although no etiologic agent or trigger is identifiable for most childhood cancers, there are some well-described associations with infectious diseases. The incidence of Burkitt lymphoma is much higher in malaria-endemic regions, Kaposi sarcoma is almost always associated with HIV infection, and hepatocellular carcinoma is more frequent in areas with a high prevalence of hepatitis B infection.1,2 Public health measures to reduce these infectious diseases will also lower childhood cancer mortality. There are 3 standard modalities … Address correspondence to Trijn Israels, MD, PhD, Pediatric Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands 1081 HV. E-mail: t.isreals{at}vumc.nl

Childhood lymphoma incidence patterns by ICCC-3 subtype in Mexico City metropolitan area population insured by Instituto Mexicano del Seguro Social, 1996-2010.

We reviewed the childhood lymphomas epidemiological data for the Mexico City metropolitan area (MCMA). Data analysis from children (0-14 years old) diagnosed with lymphoma during the period 1996-2010 was performed at the Mexican Childhood Cancer Registry. Histological subtype was determined according to the International Classification of Childhood Cancer 3 (ICCC-3). Age-adjusted incidence rates were calculated per 1,000,000 children/year by age, gender, and ICCC-3 subtype; trends, by average annual percent change (AAPC). A total of 328 lymphoma cases included in the study had an incidence rate of 11.8, showing a decreasing trend [AAPC: -3.5; CI 95% (-5.9, -1.0)], primarily due to non-Hodgkin lymphomas (NHL) and Hodgkin lymphoma (HL) mixed cellularity subtype. NHL had the major incidence (5.8), with the precursor cell subtype being the most frequent (38.3%). Nodular sclerosis was the most frequent HL subtype. The incidence of Burkitt lymphoma was low (1.3). During the study period, there was an important reduction in the not-otherwise-specified subtype of NHL, which translated into a relative increase in the IIb3 subtype [AAPC: 7.3 (1.2, 13.8)]. Low incidences of NHL and of HL and NHL were found for < 1-year-olds and for 10- to 14-year-olds, respectively. Incidence rates for children in the MCMA, particularly the < 1 and 10-14 age groups, were lower than those for developed countries. The overall male/female ratio was 2.3. There was a trend toward a reduced incidence, for some lymphoma subtypes, in particular for NOS lymphomas, which may be the result of improvement in diagnostic techniques.

Disease patterns of pediatric non-Hodgkin lymphoma: A study from a developing area in Egypt.

Non-Hodgkin lymphoma (NHL) accounts for 8-10% of all childhood cancers. NHL collectively represents various lymphoid malignancies with diverse clinicopathological and biological characteristics. In this study, we aimed to describe the epidemiological and clinicopathological characteristics and treatment outcomes of pediatric NHL patients treated at the Pediatric Oncology Unit of Zagazig University Hospital and the Benha Specialized Pediatric Hospital. We conducted a cross-sectional retrospective study by reviewing the medical records of 142 patients admitted with a diagnosis of NHL over a period of 8 years (February, 2004 to February, 2012) in these two Oncology Units. The age at presentation ranged between 2 and 15 years, with a mean ± standard deviation (SD) of 6.1±2.8 years and a male:female ratio of 1.7:1. Abdominal involvement was the most common presentation (73.2%). Burkitt's lymphoma (BL) was the most common NHL subtype (69%), followed by lymphoblastic lymphoma, diffuse large B-cell lymphoma and anaplastic large-cell lymphoma, accounting for 18.3, 10.6 and 2.1% of the cases, respectively. The majority of the patients (88.7%) had been diagnosed with advanced disease (Murphy stage III/IV). Complete remission was achieved in 120 cases (84.5%). A total of 16 patients (11.3%) succumbed to the disease during the first few months and 6 patients (4.2%) remained alive following relapse. The mean follow-up duration ± SD was 34.6±25.1 months (range, 3-84 months). The 5-year overall survival (OS) and event-free survival (EFS) rates were 88.7 and 85.1%, respectively. None of the clinical, epidemiological or pathological variables exhibited a statistically significant association with the OS or EFS. In conclusion, NHL occurs at a younger age, with a higher incidence of BL and advanced-stage disease. The outcome of NHL in our two centers was satisfactory, approaching the international rates.

Burkitt lymphoma risk in U.S. solid organ transplant recipients.

Case reports of Burkitt lymphoma (BL) in transplant recipients suggest that the risk is markedly elevated. Therefore, we investigated the incidence of BL in 203,557 solid organ recipients in the U.S. Transplant Cancer Match Study (1987-2009) and compared it with the general population using standardized incidence ratios. We also assessed associations with demographic and clinical characteristics, and treatments used to induce therapeutic immunosuppression. BL incidence was 10.8 per 100,000 person-years, representing 23-fold (95% confidence interval (CI) 19-28) greater risk than in the general population, and it peaked 3-8 years after the time of transplantation. In adjusted analyses, BL incidence was higher in recipients transplanted when <18 vs. ≥35 years (incidence rate ratio [IRR] 3.49, 95% CI 2.08-5.68) and in those transplanted with a liver (IRR 2.91, 95% CI 1.68-5.09) or heart (IRR 2.39, 95% CI 1.30-4.31) compared with kidney. BL incidence was lower in females than males (IRR 0.45, 95% CI 0.28-0.71), in blacks than whites (IRR 0.33, 95% CI 0.12-0.74), in those with a baseline Epstein-Barr virus (EBV)-seropositive versus EBV-seronegative status (IRR 0.34, 95% CI 0.13-0.93), and in those treated with azathioprine (IRR 0.56, 95% CI 0.34-0.89) or corticosteroids (IRR 0.48, 95% CI 0.29-0.82). Tumors were EBV-positive in 69% of 32 cases with results. EBV positivity was 90% in those aged <18 years and 59% in those aged 18+ years. In conclusion, BL risk is markedly elevated in transplant recipients, and it is associated with certain demographic and clinical features. EBV was positive in most but not all BL cases with results.

Incidence and trends in Burkitt lymphoma in northern Tanzania from 2000 to 2009

Burkitt lymphoma (BL) is endemic in parts of Tanzania, but there is scant country or region level data about burden and trends of BL in Tanzania over the past three decades. Here, we update baseline epidemiology of BL in northern Tanzania using recent data. Data for childhood BL diagnosed at six hospitals in Mara and Mwanza regions in northern Tanzania during 2000-2009 were compiled. Age, sex, and regional patterns were analyzed. Crude incidence rates of BL were calculated by sex, anatomic site, geographical region, and calendar year. Among 944 cases, 549 (58%) were male (male/female case ratio 1.4:1). Among those with known anatomic site (92%), facial only tumors represented a large proportion of tumors in boys than girls (50% vs. 36%, P < 0.002). Tumors occurred at a younger mean age in boys than girls (6.8 years vs. 7.6 years, P < 0.01). Crude BL incidence was 4.2 per 100,000, but varied by region (3.0 in Mwanza vs. 6.8 in Mara, P = 0.01), by district (1.4-22), by gender (5.0 in boys vs. 4.0 in girls), and by age group (2.0 in 0-4, 7.8 in 5-9, and 3.1 in 10-15 years). BL incidence peaked in 2001 and decreased gradually thereafter. Our results indicate that male sex, young age, and geographical characteristics are risk factors for BL in Tanzania. BL incidence declined with calendar year, but the significance of this finding is uncertain. Well-designed epidemiological studies of BL in Tanzania may shed light on environmental characteristics underlying these patterns.