High-dose chemotherapy followed by allogeneic stem cell transplantation in high-risk relapsed and refractory aggressive non-Hodgkin lymphoma: Results of a prospective study of the German high-grade non-Hodgkin lymphoma study group.

Abstract

8004 Background: The role of allogeneic stem cell transplantation (alloSCT) in high-risk aggressive NHL is poorly defined; the role of graft-versus-lymphoma effect is unclear. Reduced intensity conditioning has shown limited efficacy in patients with refractory disease. Methods: Patients with primary refractory disease, early relapse (<12 months) or relapse after autologous SCT of aggressive B-cell (n=61) or T-cell (n=23) NHL were enrolled from June 2004 to March 2009. Myeloablative conditioning (fludarabine 125mg/m2, busulfan 12mg/kg, cyclophosphamide 120 mg/kg) was followed by alloSCT from related (n=24) or unrelated (n=60) donors. 57/84 patients received a 10 HLA-loci compatible graft. Results: Overall survival at 3 years was 42% (95% CI, 31% to 52%), progression-free survival (PFS) was 40% (95% CI 29% to 50%). Non-relapse mortality (NRM) was 12% at 100 days and 35% at one year. Graft-versus-host disease (GVHD) and infection were the predominant causes of NRM. Relapse rate was 30% with latest relapse at day +327. Patients with an HLA fully compatible donor (plus ATG with unrelated donors) (n=40) had the best outcome (NRM at 1y 10.4 vs 57.2%, PFS at 3y 64.7% vs 31.8%, p < 0.0001). GVHD > grade I correlated with improved PFS (HR 0.45, p=0.0088). Patients with refractory disease or early relapse (n=60) experienced PFS at 3y of 33%. Conclusions: Lymphoma-debulking (high-dose) chemotherapy followed by alloSCT shows excellent results in heavily pretreated patients with early relapse or primary refractory aggressive lymphoma. There was evidence of graft-versus-lymphoma activity in this setting. For patients with a fully matched (10/10) related or unrelated donor the results compare favorably to autoSCT or alloSCT following reduced-intensity conditioning.