An effective therapy for both undifferentiated (including Burkitt's) lymphomas and lymphoblastic lymphomas in children and young adults

Abstract

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)

Results of the LMT81 protocol, a modified LSA2L2 protocol with high dose methotrexate, on 84 children with non‐B‐cell (lymphoblastic) lymphoma

“…Our results also have to be compared with those of other groups treating non-B-cell lymphomas with other intensive regimens. At the Pediatric Branch of NC1, with a treatment consisting of a four drug regimen alternating with MTX in 48 hour infusion, continuous disease-free survival for 14 lymphoblastic lymphomas was 70% [25]. In the BFM studies [5], non-B lymphomas were treated according to the same protocols as the acute lymphoblastic leukemias.…”

Oral mucositis

“…five-fluorouracil (5-FU), cisplatin, etoposide and melphalan are particularly stomatotoxic (Chi et al, 1995;Pico et al, 1998) and mucositis is common with doxorubicin, vinblastine, taxanes and methotrexate (Symonds, 1998), but uncommon with asparaginase and carmustine (Symonds, 1998). The combining of different chemotherapeutic drugs further intensifies the likelihood of mucositis: from 40% to 70% of patients treated with standard chemotherapy regimens suffer mucositis (Hickey et al, 1982;Rodu and Gockerman, 1983;Magrath et al, 1984;Schubert et al, 1984;Balis et al, 1985;Caballero et al, 1985;Carl and Higby, 1985;Bishop et al, 1986;Dreizen et al, 1986;Barrett, 1987;Sonis and Kunz, 1988;Dahllof et al, 1989;Weisdorf et al, 1989;Roth et al, 1991).…”

Population‐based prognostic factors for survival in patients with Burkitt lymphoma: An analysis from the Surveillance, Epidemiology, and End Results database

“…[2][3][4] Many of the protocols were adapted for adults based on the improved outcomes seen in pediatric patients. 5,6 With the addition of rituximab to chemotherapy, an improvement in response and survival rates in patients with BL is expected, although it had been difficult to conclusively demonstrate in small single-arm, single-institution studies. 7,8 In addition, little is known about prognostic factors for survival in patients with BL in the rituximab era, which makes patient counseling and stratification in contemporary treatment studies difficult.…”