This disease, also known as Burkitt's lymphoma, is the most common cancer of African children. D. Burkitt, a British surgeon, was the first to report extensive studies of the disease in 1958 while at Makerere College Medical School, Kampala, Uganda, East Africa. Other investigators found that the predominant characteristic, a lymphosarcoma of the jaw, was only one manifestation of widespread disease involving various other organs, such as ovaries and kidneys. The tumor grows rapidly, and, if untreated, usually causes death within 12 months. In geographic areas where Burkitt's tumor is common, acute leukemia, which causes about half of the deaths due to cancer among children in the United States and Europe, was considered extremely rare until very recently. Studies have now suggested that the incidence of acute leukemia in these areas may be significant.
A cancer primarily of African children, Burkitt's tumor, occurs most often in a geographic belt of low, humid areas across central Africa.
Burkitt's tumor is chiefly associated with a geographic belt extending across central Africa from east to west. The disease occurs almost exclusively at elevations below 5,000 feet and at temperatures above 60 degrees Fahrenheit, in regions where the annual rainfall is greater than 20 inches. This low, humid area is the habitat of man-biting African mosquitoes, among which are known carriers of viral diseases. Virus-like particles have been detected in tissue cultures of lymphoid cells of patients with Burkitt's tumor, and these are being studied intensively in attempts to find out whether this tumor is caused by a virus.
The average patient in areas where the tumor is common is younger than in other areas, and the incidence of jaw tumors is higher and that of abdominal tumors, lower. Since Burkitt's tumor is much less common in the United States and Europe, it is to be expected that the jaw tumors would be less prominent than the abdominal tumors, and this has been the case in most series of patients.
Until 1960 there was no successful therapy for Burkitt's tumor. In that year chemotherapy produced occasional successes. As with acute leukemia, the first outstanding results were achieved with the folic acid antagonists. Massive short courses of methotrexate, given in the dosage schedule originally used in treatment of choriocarcinoma, produced complete regressions, in some instances permanent, in patients with early Burkitt's tumor. This treatment was less satisfactory, however, in patients with more advanced disease. Intra-arterial infusion therapy with methotrexate to apparently localized disease in the jaw was unsuccessful, since although the jaw lesions responded rapidly, abdominal tumors developed immediately after therapy.
Systemic agents of several other classes, such as vincristine, cyclophosphamide, melphalan, orthomerphalan, and dactinomycin, have been used successfully in treating Burkitt's tumor. Cyclophosphamide has been found the most satisfactory against all stages of the disease. The usual schedule with this drug, in Africa, is a single large dose given intravenously, and repeated in two to three weeks. If complete regression follows these two doses, no further treatment is given. If, however, the tumor does not disappear completely, the treatment schedule is continued. Cytosine arabinoside, used recently, has produced total tumor regression, maintained for more than 3 months in 2 of 3 patients treated.
One of the important reasons for the keen interest of cancer chemotherapists in intensive studies of Burkitt's tumor is its sensitivity to drugs. A total of 38 out of 245 patients treated by groups of investigators in Nairobi, Kenya; Ibadan, Nigeria; and Kampala, Uganda have survived in unmaintained remission one to seven years after the start of therapy. The long-term remission rate was 15.5 percent; this was a significant achievement using chemotherapy alone. After treatment with cyclophosphamide, orthomerphalan, or methotrexate, only one patient has ever been reported as relapsing after one year of unmaintained remission. Investigators believe that most of the patients will continue to remain in remission. These studies have indicated that if the disease recurs after a few months, further treatment may still produce a long-term remission, perhaps with the use of a second or third drug when resistance to the first develops.
Another reason for scientific interest in Burkitt's tumor is that long-term remissions in the African patients appear to be due to a combination of chemotherapy and host immune defenses. The blood serums of Burkitt's tumor patients in complete remission had a higher level of antibody (specific disease-fighting substance in the blood) reactive with Burkitt's lymphoma target cells than did the serums of patients who did not respond well to chemotherapy. Reactivity was demonstrated by a test called membrane immunofluorescence test, in which serums from Burkitt's tumor patients produced a brilliant, fluorescent color in the cell membrane of Burkitt's tumor target cells. A negative reaction was a weak, pale-grey diffuse shadow, produced by the serums in control target cells. The control cells were normal bone marrow cells of Burkitt's tumor patients, normal lymph node cells, or bone marrow cells from leukemia patients. The antibodies have been found so far in the serums of only one or two patients with Burkitt's tumor in the United States.
These are Burkitt's lymphoma cells magnified many times The white areas indicate that the cells are fluorescing as a positive response to the membrane immunofluorescence test. The test is made by combining the cells grown in a test tube with serum from a Burkitt's tumor patient and staining the cells with a special reagent. Fluorescence of the cell membrane indicates that the patient's serum contains antibodies reactive with the cells.