High-Dose Sequential Chemotherapy Versus a Less Intensive Chemotherapeutic Regimen Followed by Peripheral Blood Progenitor Cell Autografting in Patients with Advanced Hodgkin's Disease.

Abstract

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is considered standard of care for patients with Hodgkin's disease (HD) who relapse or progress after first-line chemotherapy. Recently, high-dose sequential chemotherapy (HDS) before ASCT has been evaluated, and phase II data suggest that it may improve the outcome without increasing significantly the toxicity. However, the lack of comparison between HDS and a more conservative strategy hampers any conclusion about the effectiveness of HDS. In this study, we compared in a non-randomized fashion, HDS (n=52) with a less-intensive chemotherapeutic regimen (non-HDS, n=60) followed by ASCT in patients with relapsed or refractory HD. Patients were treated at 2 Brazilian centers (HDS - UNICAMP; non-HDS - UFRJ). HDS consisted of cyclophosphamide (7 g/m2) followed by stem cell collection, methotrexate (8 g/m2) plus vincristine (1.4 mg/m2) and etoposide (2 g/m2), followed by BEAM and peripheral blood ASCT. Non-HDS patients received 2 cycles of DHAP, followed by cyclophosphamide (1,5 g/m2) followed by stem cell collection, followed by CBV and peripheral blood ASCT. There were more HDS patients with advanced disease (stage IV 40% vs. 13%, p=0.001), bulky disease (62% vs. 39%, p=0.02), and less patients in complete remission (CR) (6% vs. 18%, p=0.04). Toxic death before HSCT occurred in 5 patients in the HDS group and in none in the non-HDS group (p=0.02). Among 31 patients with progressive disease (PD) in the HDS group, 8 (25% remained in PD before ASCT, compared to 100% of 28 patients in the non-HDS group (p<0.001). The actuarial survival from HSCT was similar (58% in both groups, p=0.49), as was the disease free survival (64% in HDS vs. 80% in non-HDS, p=0.19). The outcome of patients from the HDS group who were in PD at the time of HSCT was significantly poorer than patients in CR or partial remission (actuarial survival zero vs. 77%, p<0.001). On the other hand, in the non-HDS group, the overall survival was not influenced by the disease status before ASCT (60% vs. 59%, p=0.77). Although HDS was associated with early deaths, it seemed to be beneficial to patients in PD. These results suggest that HDS could be preferably selected to patients with PD.