Could the Intensification of Salvage Regimens Safely Overcome the Lymphoma Disease Resistance?

Abstract

Background Disease chemosensitivity to salvage treatment is a major predictive factor for a favorable outcome after autologous stem cell transplantation (ASCT) for patients with refractory lymphomas. Therefore the importance of effective and safe salvage regimens is indisputable. Methods We retrospectively compared the outcomes in terms of safety and efficacy, in 67 (HL:36, NHL:31) patients, with a median age of 34,5 (16-75)ys, who received as 1st salvage either DICEP [Dose Intensified Cyclophoshamide (1750 mg/m2), Etoposide (350 mg/m2), Cisplatin (35 mg/m2), days 1-3, (n=23)] or the widely used regimen ESHAP (n=44). Rituximab was additionally given to all CD-20 positive lymphoma patients. The statistical analyses based on the student's T-test, Kaplan Meir method and log rank test. Results In a total, 34 patients were evaluated with primary induction failure (PIF), 14 with early relapsed ( The overall response (>50% tumor reduction) rate was significantly superior for the DICEP regimen, reaching 83% (19/23 patients) vs. 60% (26/44 patients) for ESHAP group (p=0,04). Eleven out of 23 patients (48%) from the DICEP group and 14/44 (30%) from the ESHAP group achieved complete metabolic remission according to PET/CT criteria. The median hospitalization period was 20(5-25) days for the DICEP compared to 10(10-19) days for the ESHAP group. However, for the ESHAP group, an additional median of 21 (6-28) hospitalization days were required, since 12/18 non-responders patients admitted for a 2nd salvage treatment before ASCT. All but two patients (due to refractory disease) underwent ASCT. The 2-ys overall survival from disease diagnosis and the 2-ys progression free survival from 1st salvage treatment were similar for the two groups (95% vs. 88% and 70% vs. 78% for DICEP and ESHAP groups respectively). Two heavily pretreated patients from the ESHAP group developed secondary myelodysplastic syndrome post ASCT. Conclusion In our study both regimens demonstrated a safe profile. The extremely high response rates for DICEP regimen, finally resulted in less exposure to chemotherapeutic agents before proceeding to ASCT, that might led in less early and long term severe toxicity. Nevertheless, only prospective trials with large series of patients can clarify the role of DICE in the salvage treatment setting.