Antibody-dependent cell-mediated cytotoxicity against Epstein-Barr virus membrane antigen in African Burkitt's lymphoma.

Serial samples of sera from patients with African Burkitt's lymphoma were tested for antibody against Epstein-Barr virus (EBV)-specific membrane antigen (MA) by the antibody-dependent cell-mediated cytotoxicity assay (ADCC). Titers of patients in the long-term survivor group were generally higher than those found in the sera of patients in the short-term survivor group. Although ADCC titers to EBV-MA were not useful in predicting which patients would relapse there was a definite relationship between ADCC titer and prognosis. The individual differences in ADCC titers in patients in remission may explain the variability of responses that have been reported in studies on serotherapy with remission plasma.

Delayed hypersensitivity reactions of cancer patients to antigens on lymphoid cell lines.

Four-hundred and fifty nine cancer patients were skin tested with extracts from five lymphoid cell lines. More than 50% of patients with lymphoma had positive skin tests with the extracts prepared from the cell line derived from Burkitt's lymphoma (BL) and more than 50% of nasopharyngeal carcinoma (NPC) patients reacted to the NPC-derived cell line extracts. Although the significant association between patient diagnosis and orgin of cell lines suggested that tumor-associated antigens were responsible for the pattern of delayed hypersensitivity, problems in standardization of antigen potency and non-specificity need to be resolved before this in vivo assay achieves its full potential.

Combination chemotherapy in abdominal Burkitt's lymphoma.

In a clinical trial, 42 patients with abdominal Burkitt's lymphoma (BL) were treated with a combination regimen, code-named CVA, consisting of cyclophosphamide (CTX), vincristine, and cystosine arabinoside. In addition, intrathecal methotrexate (i.t. MTX) was administered as prophylaxis against subsequent central nervous system (CNS) involvement. Induced remissions, relapse, and survival were compared with those in a preceding group of 44 patients with abdominal BL treated with CTX along. Remission rate did not differ significantly in the two treatment groups, although induced remissions were higher in the CVA plus i.t. MTX-treated group (94% vs. 83%). Remission duration was significantly increases (p less than .05) and CNS relapse significantly reduced (p less than .05) in the group treated with CVA and i.t. MTX. The combination therapy was associated with higher early deaths during treatment, which adversely affected the overally survival. It is suggested that a reduction of the initial chemotherapeutic doses, particularly for patients with extensive tumor load, could further improve on the results of this trial.

Sequential evaluation of cutaneous delayed hypersensitivity responses to recall and to lymphoid cell line antigens in Burkitt's lymphoma.

Delayed cutaneous hypersensitivity reactions to standard recall antigens (candidin, mumps and PPD), to crude membrane extracts of a cell line derived from Burkitt's lymphoma (Raji) and to cell line derived from normal lymphocytes (F265) were sequentially evaluated in 44 patients with Burkitt's lymphoma. Sixteen patients (36%) manifested delayed hypersensitivity responses to the standard antigens and seven (16%) to the Raji membrane extract at presentation. Following successful chemotherapy, there was prompt and significant improvement of reactivity to both the standard and Raji antigens (p greater than 0.001), suggesting that the initial impairment of delayed hypersensitivity was most likely related to tumor burden. By 9 months after treatment, all patients in sustained remission expressed reactivity to Raji and 21 of 22 to the standard antigens. None of the patients skin-tested with the F265 extract at presentation gave a positive response and only one subsequently expressed reactivity after remission was induced. On relapse, reactivity to the standard antigens was more readily lost (4 of 11) then reactivity to the Raji extract (1 of 7). Pretreatment delayed hypersensitivity to the standard antigens also correlated better with long-term survival than to pretreatment responses to Raji. It remains to be determined whether the antigens expressed in the Raji extract are indeed tumor-specific or related to Epstein-Barr virus.

Sickle cell trait, hemoglobin C trait, and Burkitt's lymphoma.

In a controlled study in Ghana, the hemoglobin electrophoretic pattern in 112 patients with Burkitt's lymphoma was compared to that of their nearest neighbor controls of the same age, sex, and tribe, as well as their sibling controls. Analysis of the data obtained did not show any statistically significant protective advantage for sickle cell trait against Burkitt's lymphoma. Hemoglobin C trait appeared to offer a slight protective advantage (p less than 0.1), but this did not reach statistical significance. These results do not disprove the malaria co-factor hypothesis in the etiology of 0urkitt's lymphoma, but deprive it of an additional indirect evidence in its favor.

Relapse in Burkitt's lymphoma.

Of 109 patients with histologically confirmed Burkitt's lymphoma who completed a course of chemotherapy, 86 (79%) achieved complete remission. Forty-five (52%) of patients with initial complete remission relapsed with tumour over an observation period ranging from 2 years to over 5 years. Relapse was more common in patients who initially presented with abdominal or central nervous system (CNS) involvement than in patients who presented with localized facial tumours (p less than 0.01). Anatomical distribution of tumour on relapse differed from that at presentation. Facial bones were much less frequently involved on relapse; on the other hand, the CNS, cranial nerves, orbits and skin were frequent sites of disease on relapse. CNS involvement occurred in 42% (19/45) of patients at the first relapse and in 73% (11/15) of patients with multiple relapses. Prognosis in these patients was poor. Two relapse types were clinically identifiable. Early relapse (remission duration less than 12 weeks) was associated with frequent involvement of the CNS, drug resistance and a generally unfavourable outcome. Patients with late relapse (remission duration greater than 12 weeks) responded much better to secondary treatment. Possible pathogenic mechanisms underlying these two relapse types are discussed.

Burkitt's lymphoma: a clinical study of 110 patients.

One hundred and ten previously untreated patients with Burkitt's lymphoma were studied prospectively over a period ranging from over 1 year to 5 years. Of 103 patients who were treated with cyclophosphamide as a single agent, 79 (77%) achieved complete remission. Vincristine plus methotrexate or cytosine arabinoside induced complete remissions in only two of 24 patients who failed to respond to cyclophosphamide. Fifty-two percent of patients who entered complete remission subsequently relapsed with tumor. Relapse was significantly higher in patients who presented with disseminated disease (Stage III-IV) than in patients with localized disease (Stage I-II). Patients who relapsed early (remission duration less than 12 weeks) had a significantly worse prognosis than patients who relapsed late (remission duration greater than 12 weeks). Actuarial calculated 2- and 4-year survival for all patients was 44% and 38%, respectively. Factors that adversely affected survival were primary resistance to cyclophosphamide, early tumor relapse, central nervous system disease, and involvement of abdominal organs.

Survival of Burkitt's lymphoma patients in Ghana.

Of 141 suspected cases of Burkitt's lymphoma referred from all over Ghana between November 1965 and June 30, 1969, the diagnosis of Burkitt's lymphoma was confirmed histologically in 60. This report deals with survival of all 50 treated and evaluable cases. The overall estimated long term survival rate was 38·5% calculated actuarially. It was 63·2% for Stage I (10 of 18); 20·0% for Stage II (2 of 10); and 25·4% for Stages III and IV combined (3 of 22), thus confirming the value of staging as a rough guide to prognosis. Six Stage I patients who died all had large tumors. These results have been compared with a similar study by Morrow et al. (1967) from Uganda.