Treatment of High Risk Diffuse Large B-Cell Lymphomas (DLBCL) with Ntensive Induction Chemotherapy, Rituximab and Autologous Stem Cell Transplant.

Background. Aggressive lymphomas with high-intermediate to high risk according to IPI or age-adjusted IPI (aaIPI) have approximately 50% probability of disease progression in two years. Previous studies of CLSG have shown that intensive induction chemotherapy combined with high-dose chemotherapy and autologous stem cell transplant (ASCT) might be benefitial in these patients (

Methods. DLBCL patients of age 18–65 years and aaIPI 2 or 3 were eligible for the study. Treatment protocol consisted of three cycles of high-dose CHOP (MegaCHOP, cytoxan 3 g/m², doxorubicin 75 mg/m², vincristin 2 mg, and prednison 300 mg/m² every 21 days with G-CSF support), followed by three cycles of ESHAP and BEAM with ASCT. Peripheral progenitor cells were collected after first cycle of ESHAP. Four to six doses of R 375 mg/m² were given on day 1 of induction chemotherapy. As four treatment-related deaths occured in first twenty patients, prephase consisting of AOP (MegaCHOP without cytoxan) was incorporated into the treatment regimen from mid-2003.

Results were analysed with intend-to treat approach. Kaplan-Meier curves were constructed for survival analyses. Results. 57 patients were treated from 2002–2004. Median age was 42 years (range, 21–64), and 34 patients were males (60%). 39 patients (67%) had aaIPI 2 and 18 patients (33%) had aaIPI 3. 17 patients had mediastinal variant of DLBCL (30%), and 40 patients (70%) had DLBCL-other. Of 54 evaluable patients, 47 achieved CR or CRu (87%), 5 achieved PR (9%) and two progressed less than three months after treatment completion (4%). Six patients died due to treatment related toxicity (11%), four of them treated without prephase. Three other patients have life-threathening complications (6%). Only one patient (2%) progressed more than one year after study entry. Both 2-year actuarial overall survival (OS) and 2-year event-free survival (EFS) are 79% after median follow-up of 13 months and are not different for aaIPI 2 or 3 patients.

Conclusion. Intensive induction chemotherapy combined with rituximab and ASCT is an effective strategy for treatment of young and high risk patients with CD20 positive DLBCLs. The two-year survival rates are higher than expected especially for aaIPI 3 patients. However, the toxicity is quite severe and the advantage of this regimen is to be proven in randomized trials.