Successful Treatment of Primary Refractory Bulky Diffuse Large B-Cell Lymphomas with Concomitant Radio-Chemotherapy Followed by Autologous Stem Cell Transplantation : A Single Center Experience

Diffuse large B cell lymphomas (DLBCL) with bulky presentation display a poor prognosis because of a substantial rate of primary refractory disease. Second and third lines of standard chemotherapy associated with rituximab do not always achieve a complete response (CR) Autologous stem cell transplantation (ASCT) provides the best progression-free survival when patients are transplanted in CR. Concomitant radio-chemotherapy (CRC) has been used in the treatment of solid carcinomas, and may be useful in the treatment of locally refractory DLBCL to obtain a better tumor control with a minimal risk of systemic progression. We report 5 retrospective cases of patients (less than 60 years old) treated at our institution with CRC for bulky DLBCL with localized refractory disease assessed by CT and/or PET-Scan. All 5 patients presented at diagnosis with at least one adverse prognostic factor : 4 with elevated LDH, 4 with stage III or IV. The largest diameter of the bulky sites ranged between 70 and 160 mm. All 5 patients experienced locally refractory disease after one (2/5) or two (3/5) lines of immuno-chemotherapy, at mediastinal (2/5) or abdominal (3/5) sites. They were treated by 3 cycles of rituximab (375 mg/m² on d1), CDDP (30 mg/m² d1–3) and etoposide (120 mg/m² d1–3) at 21d intervals and concomitant radiotherapy delivered to the residual disease sites, administrated in 2 Gy fractions once daily to a total dose of 30 Gy, beginning on d21. For one patient, CDDP was replaced by carboplatin because of previous renal toxicity and another received standard DHAP together with radiation therapy as a second-line treatment. The whole procedure was feasible, with no grade III or IV toxicities. One patient died of early disease progression outside the irradiation field. Four patients out of 5 achieved a complete response and were subsequently transplanted. With a follow-up ranging between 2 and 75 months, all 4 patients are alive and free of disease as well as of long-term toxicity. These preliminary results suggest that CRC deserves further investigation as an option for the management of localized refractory DLBCL.