Did you mean: burkitt s lymphoma
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Blood Feb 2021Burkitt lymphoma (BL) is a highly aggressive, B-cell, non-Hodgkin lymphoma categorized into endemic, sporadic, and immunodeficiency-associated subtypes. BL has distinct... (Review)
Review
Burkitt lymphoma (BL) is a highly aggressive, B-cell, non-Hodgkin lymphoma categorized into endemic, sporadic, and immunodeficiency-associated subtypes. BL has distinct pathologic and clinical features, characterized by rapidly progressive tumors with high rates of extranodal involvement. Next-generation-sequencing analyses have further characterized the genomic landscape of BL and our understanding of disease pathogenesis, although these findings have yet to influence treatment. Although most patients are cured with intensive combination chemotherapy, given the paucity of randomized trials, optimal therapy has not been defined. Furthermore, treatment of elderly patients, patients with central nervous system involvement, or those with relapsed disease remains an unmet need. In this review, we highlight the clinical, pathologic, and genomic features, as well as standard and emerging treatment options for adult patients with BL.
Topics: Adult; Africa South of the Sahara; Allografts; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Biomarkers, Tumor; Burkitt Lymphoma; Central Nervous System; Disease Management; Endemic Diseases; Epstein-Barr Virus Infections; Europe; Gene Expression Profiling; Genes, myc; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Humans; Mutation; Neoplasm Proteins; Prognosis; Rituximab; Therapies, Investigational; Tumor Lysis Syndrome; United States
PubMed: 33171490
DOI: 10.1182/blood.2019004099 -
Blood Sep 2022High-grade B-cell lymphoma (HGBL), not otherwise specified (NOS), is a recently introduced diagnostic category for aggressive B-cell lymphomas. It includes tumors with... (Review)
Review
High-grade B-cell lymphoma (HGBL), not otherwise specified (NOS), is a recently introduced diagnostic category for aggressive B-cell lymphomas. It includes tumors with Burkitt-like or blastoid morphology that do not have double-hit cytogenetics and that cannot be classified as other well-defined lymphoma subtypes. HBCLs, NOS, are rare and heterogeneous; most have germinal center B-cell phenotype, and up to 45% carry a single-hit MYC rearrangement, but otherwise, they have no unifying immunophenotypic or cytogenetic characteristics. Recent analyses using gene expression profiling (GEP) revealed that up to 15% of tumors currently classified as diffuse large B-cell lymphoma display an HGBL-like GEP signature, indicating a potential to significantly expand the HGBL category using more objective molecular criteria. Optimal treatment of HGBL, NOS, is poorly defined because of its rarity and inconsistent diagnostic patterns. A minority of patients have early-stage disease, which can be managed with standard R-CHOP-based approaches with or without radiation therapy. For advanced-stage HGBL, NOS, which often presents with aggressive disseminated disease, high lactate dehydrogenase, and involvement of extranodal organs (including the central nervous system [CNS]), intensified Burkitt lymphoma-like regimens with CNS prophylaxis may be appropriate. However, many patients diagnosed at age >60 years are not eligible for intensive immunochemotherapy. An improved GEP- and/or genomic-based pathologic classification that could facilitate HGBL-specific trials is needed to improve outcomes for all patients. In this review, we discuss the current clinicopathologic concept of HGBL, NOS, and existing data on its prognosis and treatment and delineate potential future taxonomy enrichments based on emerging molecular diagnostics.
Topics: Burkitt Lymphoma; Germinal Center; Humans; Immunophenotyping; Lymphoma, Large B-Cell, Diffuse; Prognosis; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-6; Proto-Oncogene Proteins c-myc
PubMed: 34525177
DOI: 10.1182/blood.2020008374 -
Journal of Clinical Oncology : Official... Apr 2021Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for...
PURPOSE
Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches.
METHODS
We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019.
RESULTS
In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively.
CONCLUSION
The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Australia; Burkitt Lymphoma; Canada; Cohort Studies; Europe; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Prognosis; Rituximab; United States
PubMed: 33502927
DOI: 10.1200/JCO.20.03288 -
Journal of Cancer Research and Clinical... Jan 2022More than 90% of the adult population globally is chronically infected by the Epstein-Barr virus (EBV). It is well established that EBV is associated with a number of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
More than 90% of the adult population globally is chronically infected by the Epstein-Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers.
METHOD
We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein.
CONCLUSION
We estimated that EBV-related cases from these six cancers accounted for 239,700-357,900 new cases and 137,900-208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Burkitt Lymphoma; Dacarbazine; Doxorubicin; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Hodgkin Disease; Humans; Lymphoma, Extranodal NK-T-Cell; Lymphoma, Large B-Cell, Diffuse; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasms; Stomach Neoplasms; Vinblastine
PubMed: 34705104
DOI: 10.1007/s00432-021-03824-y -
Journal of Clinical Oncology : Official... Aug 2020Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late...
PURPOSE
Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma.
METHODS
We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS).
RESULTS
Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were ≥ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare.
CONCLUSION
Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Cyclophosphamide; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prednisone; Prognosis; Risk Factors; Rituximab; Survival Rate; Vincristine; Young Adult
PubMed: 32453640
DOI: 10.1200/JCO.20.00303 -
Cancer Journal (Sudbury, Mass.) 2020Despite widely available antiretroviral therapy, lymphoma remains the leading cause of death for human immunodeficiency virus (HIV)-infected persons in economically... (Review)
Review
Despite widely available antiretroviral therapy, lymphoma remains the leading cause of death for human immunodeficiency virus (HIV)-infected persons in economically developed countries. Even a few months of drug interruptions can lead to drops in the CD4 cell count, HIV viremia, and an increased risk of lymphoma. Currently, good HIV control facilitates intensive therapies appropriate to the lymphoma, including autologous and even allogeneic hematopoietic stem cell transplantation. Nonetheless, HIV-related lymphomas have unique aspects, including pathogenetic differences driven by the presence of HIV and often coinfection with oncogenic viruses. Future therapies might exploit these differences. Lymphoma subtypes also differ in the HIV-infected population, and the disease has a higher propensity for advanced-stage, aggressive presentation and extranodal disease. Other unique aspects include the need to avoid potential interactions between antiretroviral therapy and chemotherapeutic agents and the need for HIV-specific supportive care such as infection prophylaxis. Overall, the care of these patients has progressed sufficiently that recent guidelines from the American Society of Clinical Oncology advocate the inclusion of HIV-infected patients alongside HIV-negative patients in cancer clinical trials when appropriate. This article examines HIV lymphoma and includes Burkitt lymphoma in the general population.
Topics: Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Clinical Trials as Topic; HIV; HIV Infections; Hematopoietic Stem Cell Transplantation; Humans; Neoplasm Staging; Progression-Free Survival; Survival Rate; Transplantation, Autologous; Transplantation, Homologous
PubMed: 32496459
DOI: 10.1097/PPO.0000000000000448 -
Blood Feb 2023Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge...
Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.
Topics: Child; Humans; Adult; Burkitt Lymphoma; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoma, Large B-Cell, Diffuse; Mutation
PubMed: 36201743
DOI: 10.1182/blood.2022016534 -
Cytotherapy Sep 2023Epstein‒Barr virus (EBV) is a human herpes virus that is saliva-transmissible and universally asymptomatic. It has been confirmed that more than 90% of the population... (Review)
Review
Epstein‒Barr virus (EBV) is a human herpes virus that is saliva-transmissible and universally asymptomatic. It has been confirmed that more than 90% of the population is latently infected with EBV for life. EBV can cause a variety of related cancers, such as nasopharyngeal carcinoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Currently, many clinical studies have demonstrated that EBV-specific cytotoxic T lymphocytes and other cell therapies can be safely and effectively transfused to prevent and treat some diseases caused by EBV. This review will mainly focus on discussing EBV-specific cytotoxic T lymphocytes and will touch on therapeutic EBV vaccines and chimeric antigen receptor T-cell therapy briefly.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Burkitt Lymphoma; T-Lymphocytes, Cytotoxic; Immunotherapy
PubMed: 37149797
DOI: 10.1016/j.jcyt.2023.04.003 -
Blood Aug 2022Remission durability following single-antigen targeted chimeric antigen receptor (CAR) T-cells is limited by antigen modulation, which may be overcome with combinatorial...
Remission durability following single-antigen targeted chimeric antigen receptor (CAR) T-cells is limited by antigen modulation, which may be overcome with combinatorial targeting. Building upon our experiences targeting CD19 and CD22 in B-cell acute lymphoblastic leukemia (B-ALL), we report on our phase 1 dose-escalation study of a novel murine stem cell virus (MSCV)-CD19/CD22-4-1BB bivalent CAR T-cell (CD19.22.BBζ) for children and young adults (CAYA) with B-cell malignancies. Primary objectives included toxicity and dose finding. Secondary objectives included response rates and relapse-free survival (RFS). Biologic correlatives included laboratory investigations, CAR T-cell expansion and cytokine profiling. Twenty patients, ages 5.4 to 34.6 years, with B-ALL received CD19.22.BBζ. The complete response (CR) rate was 60% (12 of 20) in the full cohort and 71.4% (10 of 14) in CAR-naïve patients. Ten (50%) developed cytokine release syndrome (CRS), with 3 (15%) having ≥ grade 3 CRS and only 1 experiencing neurotoxicity (grade 3). The 6- and 12-month RFS in those achieving CR was 80.8% (95% confidence interval [CI]: 42.4%-94.9%) and 57.7% (95% CI: 22.1%-81.9%), respectively. Limited CAR T-cell expansion and persistence of MSCV-CD19.22.BBζ compared with EF1α-CD22.BBζ prompted laboratory investigations comparing EF1α vs MSCV promoters, which did not reveal major differences. Limited CD22 targeting with CD19.22.BBζ, as evaluated by ex vivo cytokine secretion and leukemia eradication in humanized mice, led to development of a novel bicistronic CD19.28ζ/CD22.BBζ construct with enhanced cytokine production against CD22. With demonstrated safety and efficacy of CD19.22.BBζ in a heavily pretreated CAYA B-ALL cohort, further optimization of combinatorial antigen targeting serves to overcome identified limitations (www.clinicaltrials.gov #NCT03448393).
Topics: Animals; Antigens, CD19; Burkitt Lymphoma; Cytokine Release Syndrome; Cytokines; Humans; Immunotherapy, Adoptive; Lymphoma, B-Cell; Mice; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Recurrence; T-Lymphocytes
PubMed: 35605184
DOI: 10.1182/blood.2022015795 -
Virchows Archiv : An International... Sep 2023Emerging entities and molecular subgroups in large B-cell lymphomas (LBCLs) were discussed during the 2022 European Association for Haematopathology/Society for... (Review)
Review
Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.
Emerging entities and molecular subgroups in large B-cell lymphomas (LBCLs) were discussed during the 2022 European Association for Haematopathology/Society for Hematopathology workshop in Florence, Italy. This session focused on newly recognized diseases and their diagnostic challenges. High-grade/large B-cell lymphoma with 11q aberration (HG/LBCL-11q) is defined by chromosome 11q-gains and telomeric loss. FISH analysis is recommended for the diagnosis. HG/LBCL-11q can occur in the setting of immunodeficiency, including ataxia-telangiectasia, and predominates in children. The morphological spectrum of these cases is broader than previously thought with often Burkitt-like morphology and coarse apoptotic bodies. It has a Burkitt-like immunophenotype (CD10+, BCL6+, BCL2-) but MYC expression is weak or negative, lacks MYC rearrangement, and is in contrast to Burkitt lymphoma 50% of the cases express LMO2. LBCL with IRF4 rearrangement (LBCL-IRF4) occurs mainly in the pediatric population but also in adults. LBCL-IRF4 has an excellent prognosis, with distinguishing molecular findings. IRF4 rearrangements, although characteristic of this entity, are not specific and can be found in association with other chromosomal translocations in other large B-cell lymphomas. Other molecular subgroups discussed included primary bone diffuse large B-cell lymphoma (PB-DLBCL), which has distinctive clinical presentation and molecular findings, and B-acute lymphoblastic leukemia (B-ALL) with IGH::MYC translocation recently segregated from Burkitt lymphoma with TdT expression. This latter disorder has molecular features of precursor B-cells, often tetrasomy 1q and recurrent NRAS and KRAS mutations. In this report, novel findings, recommendations for diagnosis, open questions, and diagnostic challenges raised by the cases submitted to the workshop will be discussed.
Topics: Adult; Humans; Child; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Chromosome Aberrations; Translocation, Genetic; Mutation
PubMed: 37555980
DOI: 10.1007/s00428-023-03590-x