We have been able to detect soluble interleukin-2 receptors (IL-2R) in pretreatment sera from 80 patients with undifferentiated lymphoma (predominantly Burkitt's lymphoma) and lymphoblastic lymphoma. The demonstration of IL-2R in lymphoma-derived cell lines by immunoprecipitation and direct staining indicates that IL-2R is synthesized by the tumor cells. Comparisons were made with two other subject groups: 42 sarcoma patients and 17 normal individuals. The distribution of soluble IL-2R values for lymphoma patients (geometric mean, 1,132 U/mL) was significantly greater than that of sarcoma patients (geometric mean, 332 U/mL; P = .0001) or normal individuals (geometric mean, 238 U/mL; P = .0001). Patients with undifferentiated lymphoma stages B, C, and D had significantly higher soluble IL-2R values (geometric mean, 1,648 U/mL) than stages A and AR (geometric mean, 706 U/mL; P = .0001) or lymphoblastic lymphoma (geometric mean, 826 U/mL; P = .0002). Within the lymphoma group, the soluble IL-2R level was found to be the most significant prognostic indicator of disease-free interval and survival when compared with other previously recognized factors such as histology, stage, bone marrow involvement at presentation, lactic dehydrogenase (LDH), uric acid (UA), and age. No factor was significantly associated with response to therapy, ie, the initial achievement of complete remission (CR) status, although small numbers of patients with a partial response limit interpretation. Soluble IL-2R levels were measured serially in two patients and were found to be elevated at presentation or relapse and to decrease to normal levels during periods of disease remission. IL-2R appears to reflect tumor burden and may prove to be a useful and specific marker for lymphoid tumors.
We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt’s lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2–16 yr) and 34 young adults 17–35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt’s lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)
We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt’s lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2–16 yr) and 34 young adults 17–35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt’s lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)
Sixty-four patients with American Burkitt's lymphoma (AMBL) treated at the National Cancer Institute were reviewed to determine the frequency and characteristics of central nervous system (CNS) involvement. Patients with minimal or completely resected tumor never had CNS disease. Of the 45 patients with more extensive disease, 15 had CNS disease: nine presented with CNS disease, six of whom subsequently had recurrent CNS disease, and six developed CNS disease only at relapse. There was a significant association between CNS and bone-marrow disease at presentation. Therapy of CNS disease consisted of short courses of intrathecal chemotherapy with cytosine arabinoside and methotrexate. Cranial irradiation was given only to patients with CNS relapse. There are six long-term survivors (LTS) who have been disease free for four to six years post chemotherapy. Of these six LTS, three presented with CNS disease, two experienced isolated CNS relapse, and one had CNS disease both at presentation and at relapse. Three of the six LTS never received cranial irradiation. It is concluded that CNS involvement in AMBL can be effectively treated, and that long-term remission, which is probably cure, can be achieved.
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