Abstract
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 (Trneny, Blood98(11) 682a, 2001). In current study, we have explored the efficacy and tolerability of this regimen in combination with antiCD20 antibody rituximab (R) for DLBCL with 2 or 3 risk factors according to aaIPI.
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.
Prospective Phase 2 Trial of High-Dose Gemcitabine/Busulfan/Melphalan (Gem/Bu/Mel) with Autologous Stem Cell Transplant (ASCT) in Hodgkin's Lymphoma Patients at High Risk of Post-Transplant Recurrence—Comparison with a Concurrent Matched Cohort