Favorable Outcome of High-Risk Mediastinal Diffuse Large B-Cell Lymphoma (DLBCL) after Dose-Intensive Chemotherapy, Rituximab and Autologous Transplant (ASCT).

Background. According to the gene expression profiling studies, mediastinal variant of DLBCL is closely related to classical Hodgkins lymphoma (HL). As dose-intensive chemotherapy markedly improves survival in advanced HL, we investigated whether the same is true for high-risk mediastinal DLBCL.

Methods. Since 1998, three studies utilising dose-intensive chemotherapy with ASCT for high-risk DLBCL (aaIPI 2–3) were conducted by Czech Lymphoma Study Group. From 1998–1999, patients were induced with 3–4 cycles of MegaCHOP every 3 weeks (Cyclophosphamide, 3 g/m2 d 1, Vincristin 2 mg d 1, Doxorubicin 75 mg/m2 d 1, Prednison 60 mg/m2 d 1–5, G-CSF 5 ug/kg from day 6) and consolidated with BEAM and ASCT (Protocol 1). From 2000–2002, patients received 3 cycles of MegaCHOP, followed by 3 cycles of ESHAP and BEAM with ASCT (Protocol 2). From 2002, 4–6 doses of Rituximab 375 mg/m2 were added to the previous regimen (Protocol 3). Outcome of patients with mediastinal DLBCL was compared with outcome of other DLBCL patients treated by the same protocols with log-rank test.

Results. 24 patients with mediastinal DLBCL with at least 12 months follow-up were identified. Their median age was 26 years (range, 21–59) and 15 of them were women (62%). 88% of patients had stage IV disease based on extensive pulmonary, pleural or pericardial involvement and 25% of patients had subfrenic disease. LDH was elevated in 88% of cases. Nine patients were aaIPI 2 (38%) and 14 patients aaIPI 3 (58%). Five patients were treated with Protocol 1 (21%), 9 with Protocol 2 (37%) and 10 with Protocol 3 (42%). 22 patients (92%) were successfully mobilized after one of the induction cycles with median 8.03x10⁶ CD34+ cells/kg collected and 21 of them were transplanted as a part of primary treatment (88%). After chemotherapy and ASCT, there were 18 CR (75%) and 4 PR (17%). Twenty patients (84%) were further consolidated by mediastinal radiotherapy because not being in CR or because of bulky disease at diagnosis. Overall, 21 patients achieved CR and one achieved PR at the end of the treatment (ORR, 92%). Two patients progressed on treatment and two other relapsed; three of these were salvaged by additional therapy. After median follow-up of 31 months (12–70), the 3-year FFS is 87% and OS is 95%. Compared with other DLBCL patients, patients with mediastinal DLBCL had significantly better 3-year survival (95% v. 64%, p = 0.007).

Conclusion. Dose-intensive chemotherapy in high-risk mediastinal DLBCL patients leads to equally good results as in advanced Hodgkins lymphoma patients. Further studies are needed with aim to reduce the treatment burden while maintaining the efficacy of the therapy.