Autologous stem cell transplantation for follicular lymphoma: no benefit for early transplant?

Autologous stem cell transplantation (SCT) is widely used as salvage treatment for patients with relapsed follicular lymphoma (FL). Although SCT can induce prolonged remissions, it does not appear to be curative in the vast majority of patients. The purpose of this study was to investigate if incorporation of SCT into first-line therapy can improve its efficacy. Fifty-five patients underwent sequential high-dose therapy as up-front (n=33) or salvage treatment (n=22) for advanced stage FL at our institution. Treatment consisted of intensive chemotherapy with dexamethasone, carmustine (BCNU), etoposide, cytarabine, and melphalan (Dexa-BEAM) for mobilization of peripheral stem cells and reduction of tumor load, followed by one of three different myeloablative regimens and SCT. With a median follow-up of 4 years, projected event-free survival (EFS) and overall survival (OS) at 4 years post transplant was 59% and 84%, respectively, with no evidence of plateau in the survival curves. By univariate and multivariate analysis weighing age, sex, stage, BM and extranodal involvement, timing of transplant, ex vivo purging, and conditioning regimen [total body irradiation (TBI) vs non-TBI], the only significant factor predicting for superior EFS and OS was up-front vs salvage transplant (4-year EFS 76% vs 38%, p=0.02; 4-year OS 92% vs 73%, p=0.033). However, when calculated from diagnosis, EFS and OS of the up-front and salvage groups were virtually identical, implying that the longer survival post SCT in the up-front group was completely compensated by the longer interval between diagnosis and transplant in the salvage group. Median OS from diagnosis was 13.5 years. Except for one case of anaplastic large cell lymphoma, secondary neoplasms have not occurred to date. In conclusion, our data indicate that SCT might improve the prognosis of patients with disseminated FL, although it is probably not curative even if applied early during the course of the disease. The optimum timing of SCT remains to be determined by the ongoing randomized multicenter trial of the German Low-grade Lymphoma Study Group. The impact of radiotherapy on the success of SCT does not seem to be as essential as originally believed.