Diagnosis and Treatment of Burkitt Lymphoma

. Burkitt lymphoma was recognised as a clinical syndrome by Denis Burkitt - an Irish surgeon who worked in British East Africa for the British Colonial Medical Service after the Second World War. Remarkably, it was not until 1957 - 10 years after his arrival in British East Africa (Uganda), that he saw a case.  The hospital Pediatrician (Hugh Trowel) asked Burkitt to see a 5 year old boy with tumours that had developed in all 4 jaw quadrants.  Burkitt could only confirm that the child had an inoperable cancer. Remarkably, just a week later, while visiting the District Hospital at Jinja (the location of the source of the Nile, he saw a second child with tumours present in all 4 jaw quadrants. This child also had palpable abdominal masses.  Since Burkitt had never seen such a tumour, he studied pediatric case records to determine whether tumours of this type had been seen previously.  As he soon discovered., a significant number of such cases has been seen.  Fortunately, a cancer registry had been established some 7 years before, and after painstakingly examining the records Burkitt was able to identify a total of 37 children who had died with jaw tumours - often multiple and often associated with tumour at various other anatomical sites, particularly the abdomen. The tumour also quite frequently involved serous membranes, the orbits, endocrine glands, ovary, breasts and central nervous system.  He also found a number of references to the tumour in the published literature.   The professor of pathology, Jack Davies, could not make a diagnosis other than "small round cell sarcoma" and it was not until 1959 that Gregory O'Conor, a young pathologist recently arrived from the USA, reviewed, with Davies, all the childhood cancers in the Kampala registry.  O'Conor concluded that the tumour was a type of lymphoma.  Remarkably, it accounted for 50% of all childhood cancers in the Kampala cancer registry.     

Determining optimal therapy for endemic Burkitt lymphoma is beset with problems, many arising from late referral and inadequate support.  These differ little from those facing pioneer chemo therapists in the 1960's.  Initially, the only feasible approach was trial and error, using drugs that had shown activity in other lymphoid diseases.  Resection of jaw tumours was clearly not feasible, but the intensity of the response to intra-arterial infusions of methotrexate infused into the tumour showed excellent local responses, but patients died from tumour in the high concentration areas.  This appproach showed dramatic results with methotrexate, demonstrating its effectiveness, but could not be used for patients with wide-spread tumour.  Vincristine and cyclophosphamide appeared to be as active as methotrexate when given intravenously and the best route oof administration of methotrexate is clearly intravenous.  These encouraging results prompted the use of chemotherapy in many children as well as comparisons of the mode of administration although the studies were not nearly as rigorous. In LMIC where even the validity of the diangosis needs to be checked and all patients monitored carefullly - which is difficult to achieve in the lowest income coutries.  as they are today.  For most drugs, the optimal dose and schedule has still not been determined, especially in the context of multiple drug regimens, but as experience of tolerance and effectiveness has increased, results have improved and in optimal circumstances in high income countries survival approaches 100%.   In the early studies  of methodtrexate by Oettgen, Burkitt and Burchannal in 1963, 2 of 31 had good responses but very few achieved long term survival and many were lost to follow up or had severe toxicity, making analysis impossible.  Soon other drugs were studied, including mustine (which gave a poor result) cyclophosphamide and vincristine.  Many patients achieved complete remission with these drugs used as single agents and and some long term results with one or two doses of these drugs were observed. Many other studies were using different drugs and doses have been performed since that time, but many factors impact upon the results, particularly late diagnosis, poor support and loss to follow up. In the INCTR study at Gulu, in which 132 patients were treated, preliminary results suggested a long term survival rate of as much as 70%.  This suggests that if these challenges could be overcome, it may be possible to cure as many as 75% of patients.  

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