Much has been written about Burkitt Lymphoma (BL), which was first described by Dr. Denis Parsons Burkitt in 1956. Burkitt Lymphoma is an uncommon type of Non-Hodgkin Lymphoma, often but not exclusively affecting children. It is a highly aggressive type of B-cell Lymphoma and often involves tissues other than lymph nodes. The disease is associated with a chromosomal translocation of the MYC gene, and under microscopic examination, the tumor cells have been described as having a “starry sky” appearance.
Following is a “Quick Start Guide” to Burkitt Lymphoma written by Dr. Jean Paul Martin and Dr. Marie-Reine Martin, Co-Founders of the Foundation for Burkitt Lymphoma Research (FFBLR), describing the key characteristics, epidemiology, and prognosis of BL.
The Key B.L. Specific Features (1):
- B.L. is the most aggressive lymphoma;
- B.L. was the first human tumor associated with a virus;
- The C-MYC was the first oncogene to be described in a lymphoma;
- B.L. has the shortest cell doubling time among all human cancer;
- B.L. is divided into three clinical variants (W.H.O. classification): sporadic, endemic and immunodeficiency associated.
The epidemiology must be considered separately in each clinical variant, and is different for adults and children:
- Rare and predominantly affecting adult men in western countries:
- 6.0 per 1 million men (3)
- 2.4 per million women (3)
- 1 to 2 % of the adults lymphomas (1)
- 40 % of the children lymphomas (1)
- The link with Epstein Barr Virus (EBV) is low: 15 to 30% (1).
Endemic B.L. (2) (4):
- Mainly children, usually 4-7 years old, more male than female
- 3 to 6 per 100,000 children (around 50 times more than in western countries)
- 30 to 50% of childhood cancer in equatorial Africa
- EBV found in nearly all cases
- Correlation with geographical area of endemic Malaria
Immunodeficiency Associated B.L. (5) (6):
- Mainly patients with HIV
- B.L. is much more frequent in immunodeficient patients: 0.2% of HIV infected patients(5); 19% of B.L. occurred among HIV infected individuals (6)
The prognosis is very different between sporadic and endemic, adults and children, and also following the stage of the disease and the age (2) (7) (10).
Among the patients treated by the current intensive regimen, the 5 years survival rate is in average:
- Around 80 - 90% for children (3)
- Between 50 - 60% for adults. (3) (7) (11)
But this average for adults is the result of very different outcome following the stage of the disease which defines the type of risk: Low risk around 70%, Low-Intermediate around 55%, High-Intermediate around 40%, High risk around 30%
There is also a big variance following the ages: 20 - 39 around 60%, 40 - 59 around 45%, and more than 60 around 30%.
More recent treatment with Rituximab (8) (10), as well as low intensity therapy (9), has demonstrated some progress.
Overal survival is low, but almost impossible to approach with the same criteria than sporadic (12) (13).
Immunodeficiency Associated B.L.:
Immunodeficiency patients with H.I.V. have an estimated 5 years survival rate around 50% (5).
The BLGSP is detailed on ocg.cancer.gov
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- Blum K A, Lozanski G, Byrd J C. Adult Burkitt leukemia and lymphoma. Blood. Nov 15 2004;104(10): 3009-3020
- Costa L J, Xavier A C, Wahlquist A E et al. Trends in survival of patients with Burkitt lymphoma/leukemia in the USA: an analysis of 3,691 cases. Blood. June 13 2013;121(24): 4861-4872
- Magrath J . Epidemiology: clues to the pathogenesis of Burkitt lymphoma. British Journal of Haematology. 2012; 156, 744-756
- Gopal S, Patel M R, Yanick E L et al. Temporal trends in presentation and survival for HIV-associated lymphoma in the antiretroviral therapy era. J Natl Cancer Inst. 2013; 105 (16): 1221-1229
- Shiels M S, Engels E A, Linet M S et al. The epidemic of non-Hodgkin lymphoma in the United States: Disentangling the effect of HIV, 1992-2009. Cancer Epidemiology Biomarkers & Prevention. June 2013; 22(6): 1069-78
- Wasterlid T, Brown P N, Hagberg O et al. Impact of chemotherapy regimen and rituximab in adult Burkitt lymphoma: a retrospective population-based study from the Nordic Lymphoma Group. Annals of Oncology.2014; 24 (7): 1879-1886.
- Prica A, Pratzer A, Cheung M C et al. Rituximab improves overall survival in patients treated with CODOX-M/IVAC for Burkitt lymphoma (BL) and B-cell lymphoma, unclassifiable, with features intermediate between Diiffuse large B-cell lymphoma and BL: a single center experience and review of the literature. Blood. Nov 15 2013; 122(21): 5093- .
- Dunleavy K, Pittaluga S, Shovlin M et al. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013; 369: 1915-1925.
- Hoelzer D, Walewski J, Dohner H et al. Improved outcome of adult Burkitt lymphoma/leukemia patients with rituximab and intensive chemotherapy: report of a large prospective multicenter trial. Blood. 2014; 124:3870-3879
- Jacobson C, LaCasce A. How I treat Burkitt lymphoma in adults. Blood. Nov 6 2014; 124(19): 2913-2920
- Ngoma T, Adde M, Durosinmi M et al. Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease. British Journal of Haematology. 2012; 158: 749–762
- Mutyaba I, Orem J, Wabinga H et al. Access to cancer chemotherapy and predictors of early mortality for childhood cancers in Uganda. Journal of Clinical Oncology. 2013; Vol 31,n°15 supplement: 10070
In this short video, Dr. Jean Paul Martin, accompanied by his wife and Co-Founder of the Foundation for Burkitt Lymphoma Research, Dr. Marie-Reine Martin describes two of the characteristics of BL: most aggressive tumor in children, and the first cancer linked with a virus, the Epstein Barr Virus.
Scientific Definition and Genetic Findings
In this video Dr. Riccardo Dalla-Favera, Director of the Institute for Cancer Genetics at Columbia University, and member of the Foundation for Burkitt Lymphoma Research Scientific Advisory Board discusses the subtypes of the disease, alteration of the MYC gene, link to Malaria infection, and need for better treatment in developing countries were the disease is endemic.
History of Burkitt Lymphoma
Dr. Corey Casper, Chief Executive Officer, Infectious Disease Research Institute; Affiliate Member, Fred Hutchinson Cancer Research Center; member of the FFBLR Scientific Advisory Board; and Investigator for the Burkitt Lymphoma Genome Sequencing Project (BLGSP) describes in this video how Dr. Denis Burkitt operated on a child in Kampala, Uganda with Burkitt Lymphoma, and tumor tissue from that surgery provided Sir Anthony Epstein the opportunity to identify the presence of a virus, which was named after him, in the tumor tissue. Dr. Casper also describes the establishment of the Uganda Cancer institute.
There are several major unmet needs in the clinical management of BL that require urgent attention. First, current chemotherapy is ineffective in roughly 30% of cases, and is associated with therapy induced toxicity and death. Because of the toxicity, patients with BL over the age of 70 are ineligible for this potentially curative therapy. Second, young individuals exposed to these intensive regimens face the real possibility of secondary malignancies years later. Finally, children with endemic BL in Africa, in general do not receive these curative chemotherapy regimens because of the lack of hospital support for the management of post-treatment infections, and consequently many will die of their disease. What is needed, therefore, are new approaches to the therapy of BL that are based on an understanding of its molecular pathogenesis and the regulatory pathways that it utilizes for proliferation and survival.
Treatment Paradigms and Principles:
The need for improved treatment with less toxicity is emphasized in this video by Dr. Kieron Dunleavy, Director of Lymphoma Research at George Washington University and previous Investigator for the Burkitt Lymphoma Genome Sequencing Project. Dr. Dunleavy is accompanied by Dr. Wyndham Wilson, Head, Lymphoma Therapeutics Section, Senior Investigator of the Lymphoid Malignancy Branch at NCI, and Investigator for the BLGSP.
In this video Dr. Louis Staudt, Chief, Lymphoid Malignancies Branch NIH, NIH Distinguished Investigator NIH, Director Center for Cancer Genomics, NCI, and member of the FFBLR Scientific Advisory Board, also emphasizes the need for less toxic therapies to treat BL. He discusses potential molecular events and mechanisms that may lead to less toxicity in the treatment of the disease.
Treatment of Burkitt Lymphoma in Developed Countries:
Dr. Wilson, accompanied by Dr. Dunleavy discusses the promising results from a recent NIH/NCI clinical trial using less intense, shorter duration of chemotherapy infusion, in treatment of patients with mostly sporadic Burkitt Lymphoma
Challenges and Opportunities in Treating Burkitt Lymphoma in Developing Countries
In this video Dr. Corey Casper talks about the current treatment of endemic Burkitt Lymphoma in Sub-Saharan Africa and the prognosis and challenges in treating endemic Burkitt Lymphoma.
Dr. Marie-Reine Martin emphasizes the high mortality in children with endemic Burkitt Lymphoma.
Dr. Wyndham Wilson discusses the issues and the barriers facing successful treatment of children with endemic Burkitt Lymphoma, and what the ideal characteristics of therapy should be.
Dr. Kieron Dunleavy identifies an ongoing study in Europe that will try to replicate recent findings from the NIH/NCI study using the less intense, shorter duration of chemotherapy infusion. He also discusses further plans at NCI to conduct a larger, multi-center trial in patients with various types of lymphoma.