Different Types Of non-Hodgkin Lymphoma Research Articles

Abstract 1216: Virome characterization in different types of non-Hodgkin lymphoma

Abstract Non-Hodgkin's lymphoma (NHL) is a heterogeneous group of lymphoid tissue neoplasms, with different clinical, genetic and morphological aspects. It is the most common form of hematological malignancy worldwide. In addition to risk factors, some infectious agents cause or are related to the risk of developing NHL. These include Epstein Barr virus (EBV), human herpes virus 8, human T-cell lymphotropic virus type 1, human immunodeficiency virus, hepatitis C virus, and the H. pylori. Overall, cancer attributable to infections accounted for 15.4% of new cases in 2012, and this number may increase due to improvements in molecular methodologies. Recently, other infectious agents have been associated with NHL, such as human pegivirus and cutavirus. Although factors related to immune function and the infectious agents described play a relevant role in the etiology of NHL, these factors do not explain most cases, suggesting that others factors or infectious agents could be involved in NHL development. Identifying possible pathogens associated with NHL and understanding the cancer-infectious agents relationship is essential for the development of prevention and screening aproaches. The aim of this study is to characterize the viral composition of the tumor microbiome in different types of NHL. Tumor tissue samples from NHL stored at the Brazilian National Cancer Institute were processed for viral DNA and RNA extraction. The viral nucleic acids were prepared for 19 samples with the Nextera XT kit and sequenced on an Illumina MiSeq platform. Virus identification analyses were performed by comparing the sequences obtained with viral sequences in the GenBank database through the BLASTX tool. Most samples were from diffuse large B cell lymphoma (DLBCL; n = 11), followed by marginal zone and follicular lymphoma (three cases each), and small lymphocytic and non-B, non-T cell lymphoma (one case each). A median of 46% of the obtained reads mapped to the human genome. Among the remaining reads, four viral families were identified: Anelloviridae, Flaviviridae, Herpesviridae and Papillomaviridae. EBV, a herpervirus associated with different types of NHL, was found in one gastric DLBCL. Anelloviridae reads included only the genus Alphatorquevirus and were found in five DLBCL. This virus family has a ubiquitous presence, without any clinical manifestation so far described in humans. However, anellovirus viral load has been associated with the subject’s immune status. Different human papillomaviruses from the Alpha, Beta and Gamma genera were found in six samples, comprising follicular lymphoma and DLBCL. The flavivirus human pegivirus was found in one DLBCL. Some recent studies associated this later virus with risk of lymphoma. In summary, this study describes the viral diversity found in NHL, showing the presence of viruses not yet associated with this neoplasia. Additional studies are warranted to clarify the role of these viruses in the etiology of NHL. Citation Format: Juliana D. Siqueira, Esmeralda A. Soares, Marcelo A. Soares. Virome characterization in different types of non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1216.

Second Primary Malignancies in Patients with Non-Hodgkin Lymphoma

Introduction: Increased risk of second primary malignancies (SPMs) has been reported in Hodgkin lymphoma as well as non-Hodgkin lymphoma (NHL) patients. NHLs are heterogeneous with different genetic, immunophenotypic, and clinical features. Some NHLs are aggressive but potentially curable, such as Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), while other NHLs are indolent but generally incurable, such as follicular lymphoma (FL) and marginal zone lymphoma (MZL). We hypothesized that the risk for developing SPMs in patients with different types of NHL would differ significantly. In this study, we compared the incidences of SPMs in patients with various major types of NHL, including BL, DLBCL, mantle cell lymphoma (MCL), FL and MZL, using population-based cancer registry data.Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with NHL. While the most updated database includes 1973-2014 data, only the more recent 1991-2014 data were used in this study. NHL cases were identified using International Classification of Disease for Oncology, third edition (ICD-O-3) morphology codes (BL: 9687; DLBCL: 9680; MCL: 9673; FL: 9690, 9691, 9695, 9698; MZL: 9699). The SEER sequence number was used to limit the study population to those who had NHL as their only primary malignancy throughout their lives (code 00), and those who had multiple primary malignancies with NHL as their first malignancy (code 01). For the latter group, information on SPMs was obtained by using the same patient code and a defined sequence number (code 02). Further study criteria included age 18 or greater, pathology confirmation of malignancy diagnosis, and having active follow-up. Categorical data were analyzed using Chi-square test, and time-to-event data were analyzed using Kaplan-Meier estimator. Case identification and all statistical analyses were performed using SAS (v9.4).Results: A total of 154,961 patients were included in the final analyses, 3,716 with BL, 80,734 with DLBCL, 8,323 with MCL, 44,055 with FL, and 18,133 with MZL. SPMs developed in 14,357 patients, with an overall incidence of 9.26%. The incidences of SPMs varied significantly in patients with different types of NHL, with a rate of 5.22% in BL, 7.34% in DLBCL, 9.14% in MCL, 11.66% in FL, and 12.90% in MZL (Table 1). The differences of SPM incidences between any two types of NHL were statistically significant (all P < 0.05). Male and female patients with BL had similar incidences of SPMs (5.04 % vs 5.72%, P= 0.45). Male patients with DLBCL (7.98% vs 6.58%), MCL (9.58% vs 8.16%), FL (12.69% vs 10.63%) and MZL (14.46% vs 11.62%) had higher incidences of SPMs compared to female patients (all P < 0.05). Hematological malignancies (leukemia and other lymphomas) were the most common SPMs in patients with all types of NHL. With one exception (second lung cancer in BL patients), the most common solid SPMs in NHL patients were lung cancer, prostate cancer, and breast cancer, followed closely by colorectal cancer, consistent with the pattern in general population. The next most common solid SPM was melanoma, as opposed to bladder cancer in the general population. Thyroid cancer, while less common, occurred early in patients with NHL, with the shortest median time to develop SPM.Conclusions: Close to 10% of patients with NHL developed SPMs. The incidence of SPMs correlated with the aggressiveness and potential curability of NHL, with the lowest SPM incidence in BL, followed by DLBCL, MCL, FL and MZL. Male DLBCL, MCL, FL and MZL patients had higher incidences of SPMs compared to female patients. Hematological malignancy was the most common SPM in NHL patients. The most common solid SPMs in NHL patients were lung, prostate, breast, colorectal cancers and melanoma. Thyroid cancer as a SPM tended to develop early in NHL patients. Patients with NHL must be followed long-term for SPM, a potential complication of survival. [Display omitted] DisclosuresNowakowski:Morphosys: Consultancy, Research Funding; pharmacyclics: Consultancy; Abbvie: Consultancy; Genetech: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Nanostring: Research Funding; celgene: Consultancy, Research Funding. Wang:Juno Therapeutic: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Kite Pharma: Research Funding; BeiGene: Research Funding; Oncoceutics: Research Funding; Novartis: Research Funding; Karus: Research Funding; Oncternal: Research Funding; Celgene: Honoraria, Research Funding; Asana: Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding.

High-dose polychemotherapy with autologous hematopoietic stem cell transplantation in children with non-Hodgkin lymphomas

High-dose polychemotherapy with autologous hematopoietic stem cell transplantation in children with non-Hodgkin lymphomas

Immunohistochemical subtypes of non-hodgkin lymphomas with special emphasis on diffuse large B-cell lymphoma: An epidemiological study in a tertiary care center of Eastern India

Background: Non-Hodgkin lymphoma (NHL) is a heterogeneous disease with respect to etiology, morphology, immunohistochemistry, and prognosis. Diffuse large B-cell lymphoma (DLBCL) is categorized into two subtypes – germinal center B-cell like (GCB) and activated B-cell like, based on the stage of B-cell differentiation. The epidemiologic profile of NHL varies from one place to another. The aim of the present study was to delineate the frequencies of different types of NHL including subtypes of DLBCL in a tertiary care center. Another objective was to determine if there is any correlation between different subtypes of DLBCL and clinicopathological parameters. Materials and Methods: Immunohistochemical (IHC) examination was done on paraffin blocks of patients diagnosed as NHL by histopathological examination. The patient details, type of NHL including subtype of cases of DLBCL, diagnosed by IHC, were recorded. Results: The mean age of the study population of 62 patients was 53 ± 14.5 years. Forty patients (65%) were male and 22 (35%) were female. The majority (56, 90%) of the NHLs were of B-cell type. DLBCL was the most common B-cell lymphoma (23, 41%). GCB subtype (12, 21%) of DLBCL was slightly more frequent than non-GCB type (11, 20%). The correlation between subtypes of DLBCL and clinicopathological parameters was not statistically significant. Peripheral T-cell lymphoma was the most common type of T-cell lymphoma. Most of the NHLs presented with nodal involvement (38, 61%). Conclusion: The heterogeneity of NHLs in different parts of the country makes it necessary to undertake epidemiological studies so that patient care may be improved.

Preliminary evidence of imaging of chemokine receptor-4-targeted PET/CT with [68Ga]pentixafor in non-Hodgkin lymphoma: comparison to [18F]FDG

BackgroundIn order to study the CXCR4 expression with [68Ga]pentixafor PET in different types of non-Hodgkin lymphoma, we performed a retrospective study to describe the [68Ga]pentixafor PET/CT imaging in a spectrum of lymphomas and to compare it with [18F]FDG PET/CT.ResultsTwenty-seven patients with newly diagnosed non-Hodgkin lymphoma were recruited retrospectively. [68Ga]pentixafor PET showed increased radioactivity in lymphoplasmacytic lymphoma (n = 8), marginal zone lymphoma (n = 4), diffuse large B cell lymphoma (n = 3), follicular lymphoma (n = 2), mantle cell lymphoma (n = 1), unclassified indolent B cell lymphoma (n = 3), and enteropathy associated T cell lymphoma (n = 3). However, peripheral T cell lymphoma, not otherwise specified (n = 1), and NK/T cell lymphoma (n = 2) were not avid for [68Ga]pentixafor. In comparison to [18F]FDG PET, [68Ga]pentixafor PET demonstrated more extensive disease and higher radioactivity in lymphoplasmacytic lymphoma and marginal zone lymphoma.ConclusionCXCR4 expression varies in different types of non-Hodgkin lymphoma. Overexpression of CXCR4 was detected with [68Ga]pentixafor PET/CT in lymphoplasmacytic lymphoma, marginal zone lymphoma, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, unclassified indolent B cell lymphoma, and enteropathy associated T cell lymphoma. The uptake of [68Ga]pentixafor was higher than [18F]FDG in lymphoplasmacytic lymphoma and marginal zone lymphoma.

Frequency of Different Types of Non-hodgkin Lymphoma and their Association with Demographics and Stage of Disease: An Institutional Perspective from Pakistan

Introduction: Lymphoma is the fifth most common cancer and affects both genders throughout the world. The purpose of current study is to find out the frequency of different types of Non-hodgkin lymphoma and its association with age, gender and stage of disease in Pakistani population. Methods: It was a retrospective study conducted at Department of Oncology, Liaquat National Hospital. The study included all patients with histopathological diagnosis of NHL that reported in adult oncology outpatient department from year 2005 to 2015. The pertinent clinical information and demographic data of all the patients were recorded. RESULTS: Total of 214 cases of NHL were reported between 2005 and 2015. Out of 214 patients, 113 (52.8%) were males and 101 (47.2%) were females. The mean age at diagnosis was 50.85 ± 15.64 years. Most of the cases were B cell lymphomas (n=189, 88.32%), had intermediate tumor grade (n=150, 74.61%) and stage 3 disease (n=55, 26.19%). Half of the cases had nodal presentation (n=114, 53.27%). Diffuse large B cell lymphoma was the most common type (n=140, 65.42%), followed by follicular lymphoma (n=17, 7.94%) while the most rare type was T lymphoblastic leukemia/lymphoma (n=3, 1.40%). Age (p&lt;0.001), gender (p=0.001) and tumor grade (p&lt;0.001) were significantly different among subtypes. CONCLUSION: Non-hodgkin lymphoma has different presentations in different geographic locations which could be due to different environmental and lifestyle factors. In our study the male population was predominantly affected. Intermediate grade and nodal lymphomas were more frequent and the median age of presentation was lower than the rest of the world.

The Minimal Residual Disease in Non-Hodgkin's Lymphomas: From the Laboratory to the Clinical Practice.

Minimal residual disease (MRD) in non-Hodgkin's lymphomas (NHLs) still represents matter of interest and debate: indeed, the new available treatments offer higher rates of complete responses and MRD negativity than in the past, with a positive impact on the long-term survival. Furthermore, the introduction of more sensitive and accurate molecular techniques, such as digital PCR (ddPCR) and the next generation sequencing techniques (NGS), increased the possibility of identifying molecular targets to be followed after therapy (such as rearrangement of immunoglobulins, fusion genes, or mutations). This review focused on how molecular biology can help to detect MRD in different types of NHLs and how MRD can change the clinical practice in 2019. In follicular lymphoma (FL), contamination of the grafts and molecular disease persistence after transplantation represent a negative prognostic factors. The combination of Rituximab or Obinutuzumab with Bendamustine seems to be the most effective way to clear MRD in FL patients receiving chemo-immunotherapy (further studies are in progress), and also 90Yttrium-Ibritumomab-Tiuxetan offers a deep clearance of molecular disease. Finally, molecular MRD can further stratify PET-negative cases, with subjects both PET- and MRD-negative presenting the best outcome. In aggressive lymphomas, MRD has a relevant prognostic power and can represent the platform for immunotherapy (such as CAR-T). In diffuse large B-cell lymphoma (DLBCL), the assessment of MRD in the plasma (where cell-free DNA and exosomes circulate) seems to be more predictive than the bone marrow analysis or peripheral blood mononuclear cells. Finally, NGS technologies could be more useful than the classical “patient allele-specific PCR” because they can identify any possible clone emerging during the treatment or follow-up, even if different from that identified at diagnosis, thus predicting relapse. After all, the present available molecular approaches can move MRD from the bench side to the clinical practice.

The Association between Hepatitis B Virus and Non Hodgkin’s Lymphoma in Sudanese Patients in Gezira State Sudan

The incidence of non-Hodgkin lymphoma (NHL) is steadily increasing worldwide. According to the Globocan 2008, NHL is ranked as the 12 most common cancer worldwide and the 4 most common cancer in Sudan. Sudan is endemic with hepatitis B virus (HBV) infection. Objectives: The objective of this study was to identify the association between NHL and HBV infection in Sudanese patients, Gezira State. Methods: This was cross sectional case-control study was conducted at the, National Cancer Institute (NCI) University of Gezira, during the period from 2007 to 2008. A total of 81 non-Hodgkin lymphoma patients and 95 hospitals based controlled of matched age and sex, were included in the study. All patients and control had their serum screened for the presence of HBsAg by ELISA and HBV DNA was tested using polymerase chain reaction (PCR). The Statistical Program for Social Science (SPSS16.0) was used for all statistical analyses, and test of significance. Results: The mean age of NHL patients was 37.9±23.6 years with a range (1-85 years). Male to female ratio was 1.9 to 1. There were different types of NHL in this study with the majority being B-cell lymphoma 70.4% (57/81), 49.38% (40/81 ) were positive by PCR, Original Research Article International Journal of TROPICAL DISEASE & Health, 4(8): 860-868, 2014 861 while controls 20/95 (21.05%) with significant difference between cases and controls (P<0.05). There was a significant association between B-cell subtype and HBV by both serological and molecular methods (OR= 6.5 95% CI: 1.3 32.5) and (OR= 3.6 95% CI: 0.8 – 07.4). Conclusion: This study concludes that there is a significant association between HBV and the development of NHL in Sudanese patients in Gezira State the finding provides evidence supporting the hypothesis that HBV infection may have an association with the development of NHL patients.

Clinical development of phosphatidylinositol 3-kinase inhibitors for non-Hodgkin lymphoma

Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is extensively explored in cancers. It functions as an important regulator of cell growth, survival and metabolism. Activation of this pathway also predicts poor prognosis in numerous human malignancies. Drugs targeting this signaling pathway have been developed and have shown preliminary clinical activity. Accumulating evidence has highlighted the important role of PI3K in non-Hodgkin lymphoma (NHL), especially in the disease initiation and progression. Therapeutic functions of PI3K inhibitors in NHL have been demonstrated both in vivo and in vitro. This review will summarize recent advances in the activation of PI3K signaling in different types of NHL and the applications of PI3K inhibitors in NHL treatment.

ROR1 expression is not a unique marker of CLL

Recent studies have identified receptor tyrosine kinase-like orphan receptor 1 (ROR1) on the surface of chronic lymphoid leukaemia (CLL) cells. In order to determine whether ROR1 expression is a suitable surrogate marker for the diagnosis of CLL we analysed the mRNA level of ROR1 in different types of non-Hodgkin lymphomas (NHL), and detected elevated levels of ROR1 compared to control peripheral mononuclear cells in several entities (CLL ≥ mantle cell lymphoma (MCL) > marginal zone lymphoma (MZL) >> diffuse large B-cell lymphoma > follicular lymphoma). ROR1 protein was expressed intensely on the cell surface of lymphoma cells with leukaemic blood count detected by three colour immunofluorescence. Our results indicate that ROR1 expression is not limited to CLL cases, but it is more prevalent in NHLs, mainly in MCL where it is expressed intensely and MZL where it is expressed moderately, suggesting a general role of ROR1 in lymphoma genesis and/or maintenance. Copyright © 2010 John Wiley & Sons, Ltd.

Follicular dendritic cells in follicular lymphoma and types of non‐Hodgkin lymphoma show reduced expression of CD23, CD35 and CD54 but no association with clinical outcome

Follicular dendritic cells (FDC) are specialized antigen-presenting cells found exclusively in the germinal centre (GC), which can be detected in B cell non-Hodgkin lymphomas (NHL) as reactive bystander cells. Recently, gene expression profiling has revealed that FDC networks might be associated with clinical outcome in follicular lymphoma. The aim was to characterize FDC in NHL and to evaluate a possible association with outcome in follicular lymphoma. The extent and immunophenotype of FDC was determined semi-quantitatively in reactive GC and NHL (follicular lymphoma, angioimmunoblastic T cell lymphoma, mantle cell lymphoma) using fluorescence double staining and digital image analysis. In all NHL tested CD23 and CD35 and CD54 were expressed at relatively low levels on FDC, comparable to FDC found in the dark zone of the GC. However, the extent of FDC networks did not correlate with the clinical outcome of 102 patients with follicular lymphomas treated within a prospectively randomized trial. FDC found in different types of NHL show quantitatively reduced expression of several proteins, suggesting that there are functional differences between FDC in normal GC and NHL. The extent of the FDC networks in follicular lymphoma is not useful as a prognostic marker.

Biomarkers and Prognosis in Malignant Lymphomas

Approximately 100 hematologists and pathologists from Europe, the United States, and Canada participated in the workshop Biomarkers and Prognosis in Malignant Lymphomas, held in Mandelieu, France, April 11-13, 2008, under the leadership of Anton Hagenbeek, Randy Gascoyne, and Gilles Salles. International experts in the field (discussed herein) shared their experiences in exploring the role of a variety of biologic markers related to different types of non-Hodgkin lymphomas (follicular, diffuse large B-cell, mantle cell, and Burkitt lymphomas) as well as Hodgkin lymphoma. The final goal of this clinical research is to develop new biologic prognostic indices for these major subtypes of lymphoma. In recent years, various prognostic indices, mainly based on clinical characteristics of the patient at diagnosis, have served to determine the prognostic profile and to develop prognostic factor—based treatment strategies. However, it is now time to reconsider this based on the wealth of new biologic information directly related to lymphoma cells and the surrounding cells. In this workshop, organized by the European School of Hematology and the European Hematology Association, the latest developments on molecular pathogenesis, new biomarkers, and their relation to prognosis were extensively discussed. Herein, the major conclusions presented in the different sessions are summarized.

Expression of Circadian Core Clock Gene Per2 Is Markedly Down-Regulated in Diffuse Large B-Cell Lymphoma

Non-Hodgkin's lymphoma (NHL) is a heterogeneous clinicopathologic entity characterized by distinct cells of origin, cytogenetic and molecular aberrations. In vivo studies recently showed that mice deficient in Period (PER) 2 developed lymphomas. Furthermore, we and others have recently suggested that the core circadian clock genes Period (Per)1 and Per2 have been linked to DNA damage response pathways. We showed that both genes are involved in tumor suppression by regulating cell cycle- and apoptosis-related genes. In mammals and other vertebrates, heterodimers of the basic helix-loop-helix-PAS transcription factors, CLOCK and BMAL1, activate transcription of the Period and Cryptochrome (Cry1 and Cry2) genes via binding to E-box sequences in their promoters. Subsequently, the PER and CRY repressor proteins accumulate in the nucleus and inhibit CLOCK:BMAL1 complexes, thereby inhibiting their own gene expression. This forms the major negative circadian feedback loop. In the present study, we focused on Per1 and Per2 and their role in different types of NHL. Real-time reverse transcriptase-polymerase chain reaction (real time RT-PCR) was performed to determine the mRNA expression levels of Per1 and Per2 in patients with diffuse large B-cell lymphoma (DLBCL; n = 37), mantle cell lymphoma (MCL; n = 12), follicular lymphoma (FL; n = 12), and Burkitt's Lymphoma (n = 6) compared to human normal tonsil samples (n = 10). We further tested their expression in 14 different human lymphoma cell lines. The relative expression of Per2 was markedly down-regulated in all DLBCL samples compared to normal tonsils (mean fold change: − 20.5 ± 28.7; p < 0.001). On the other hand, levels of expression of Per2 in samples of either MCL (2.5 ± 2.6; p = 0.1), FL (1.1 ± 10; p = 0.9), or Burkitt's Lymphoma (− 1.1 ± 2; p = 0.07) showed no significant change compared to the normal tonsils. Moreover, we found no significant regulation of the mRNA levels of Per1 in any of the four NHL subtypes. We confirmed our results by showing concordant results in human lymphoma cell lines. Again, Per2 expression levels were persistently down-regulated in the 7 DLBCL cell lines (OCI-Ly1, -Ly4, -Ly7, -LY10, and SUDHL-4, -6, -16; mean fold change: − 8.6 ± 5.7; p < 0.001) compared to normal tonsils, but not in MCL (SP-49, Jeko-1, NCEB-1), FL (FLK-1), Burkitt's lymphoma (Daudi), and B-precursor acute lymphoblastic leukemia (Nalm-6, BALL-1) cell lines (p > 0.05). Western blot protein analyses showed easily detectable levels of PER2 in tonsil samples, but the protein was either not expressed or significantly reduced in expression in human DLBCL cell lines. In summary, our results strongly suggest for the first time that the disruption of the key circadian clock gene Per2 may play a role in the development of DLBCL.

Expression of C‐IAP1, C‐IAP2 and SURVIVIN discriminates different types of lymphoid malignancies

(De-)regulation of apoptosis plays an important role in normal and malignant lymphopoiesis. Apoptosis-regulating genes of the BCL-2 family and the recently identified inhibitors of apoptosis (IAP) family have been implicated in different types of non-Hodgkin lymphoma (NHL). To investigate whether expression of specific apoptosis-regulating genes correlated with different types of lymphoid malignancies, we measured the expression of five BCL-2 family genes, four IAP family genes and SMAC by real-time quantitative polymerase chain reaction in patient samples. In total, 137 samples from B- and T-cell acute lymphoblastic leukaemia (ALL), B-cell chronic lymphocytic leukaemia (CLL), six different NHL types and three control tissue types were analysed. The data were further analysed using cluster and discriminant analysis. Three specific expression patterns were identified for CLL, ALL and NHL respectively. CLL samples, as well as B-ALL and follicular lymphoma samples showed high similarity in the expression of these apoptosis-regulating genes and could be distinguished from each other and other diseases and controls. Discriminant analysis identified three members of the IAP family, C-IAP1, C-IAP2 and SURVIVIN, as the most informative genes to discriminate between these lymphoid malignancies.

Management of pediatric non-Hodgkin's lymphoma

Over the past 15 years, significant progress has been made in the understanding of the molecular mechanisms involved in malignant transformation of lymphocytes as well as in the management and treatment of non-Hodgkin's lymphoma (NHL) in childhood. Cyto-histological classifications and immunophenotyping of different types of NHL have contributed to the characterisation of three major subtypes of NHL in children i.e. Burkitt's lymphoma (BL), lymphoblastic lymphoma (LL) and large cell lymphoma (LCL). Precise staging of the disease at diagnosis is necessary before the onset of the treatment and should be performed as quickly as possible. Presence of bone marrow and central nervous system (CNS) involvement are major prognosis criteria. In most cases, surgery has no therapeutic role and is required only for diagnostic procedures. Similarly, several studies have demonstrated that irradiation of various sites including the CNS does not improve survival. Thus, NHL patients are usually treated with chemotherapy alone. BL and LL have distinct clinical presentations and require completely different chemotherapy protocols. After comparable induction phases with intensive chemotherapy regimens, the former is usually treated with a short consolidation phase while the latter receives a long lasting consolidation consisting of intermittent chemotherapy for at least one year. The prognosis of stage I–II, and III–IV bone marrow negative NHL of children is excellent with respectively 95% and 75% long term survival. However, patients with concomittent CNS and bone marrow involvement in both histological subtypes have a considerably worse prognosis with only 30% long term survival. Treatment of relapse is currently under investigation and usually includes high dose chemotherapy regimen followed by bone marrow transplantation in patients experiencing a response after second line conventional dose chemotherapy. Cure after relapse is achieved in 25–40% of the cases.