Place of low-dose total body irradiation in the treatment of localized follicular non-Hodgkin's lymphoma: Results of a pilot study

Abstract

In a first prospective nonrandomized trial, 107 patients with Stage III and IV "low-grade" lymphomas have been treated with a combination of chemotherapy and low-dose total body irradiation (LD-TBI). This study shows that this scheme of LD-TBI was very well tolerated, gave a high response rate (83%), and extended RFS. It incited us to start a pilot study on localized follicular lymphomas. From January 1986 through October 1994, 34 patients with previously untreated localized low-grade non-Hodgkin's lymphomas have been included in a prospective trial with LD-TBI followed by radical involved field radiotherapy (IF-RT). Patients received two courses of whole body irradiation of 0.75 Gy in 5 fractions and 1 week separated by a rest period of 2 weeks. After 1 month, patients were reevaluated, and received 40 Gy in 20 fractions, and 4 weeks on initially pathological lymph node areas. Eight patients have been excluded from the study: 4 after histologic review (2 centrocytic, 1 lymphocytic, 1 centroblastic) and 4 patients with Stage IV because of bone-marrow involvement. The remaining 26 patients were 11 men and 15 women, 50 years old median age (mean: 50.2; range: 35-73.5) with clinical Stage I (10 pts), II1 (8 pts), and II2 (8 pts). All patients received the planned treatment. Clinical tolerance was excellent, and the hematological follow-up shows a mean nadir value of 3.9.10(9)/l (2.1-8.1) for leucocytes, 13.4 g/l (10.8-15.4) for hemoglobin, and 124.10(9)/l (46-216) for platelets, with a median delay of 3.2 months. Of 26 patients, 24 achieved complete remission (CR) after the LD-TBI that was before the IF-RT. All patients, except one, were in complete remission after IF-RT. Nineteen patients remain alive without any evidence of disease, with a median follow-up of 56.2 months. Five patients relapsed; 3 of them died. As delivered, this schedule of LD-TBI give a very high rate of CR in localized follicular non-Hodgkin's lymphoma, with a very good tolerance. It remains to prove that this immediate efficacy has an impact on long-term disease-free survival in such patients, and to understand how the LD-TBI works (direct and/or indirect induction of apoptosis; relationship with t(14;18) translocation and overexpression of bcl-2). These will be the two aims of a new EORTC prospective randomized trial comparing LD-TBI followed by IF-RT vs. IF-RT alone.