Have we found the right patient population for transplantation in follicular lymphoma?

The management of follicular lymphoma (FL) is clinically challenging, in part because of the heterogeneous outcomes. A single-institution cohort of 257 patients diagnosed in the rituximab era between 1997 and 2003 demonstrated a 10-year overall survival (OS) rate of 72%. Within this group, 60% of the patients did not require therapy at their initial presentation, and the median time to first treatment in this group was 2.9 years. This observation was corroborated by prospective trials suggesting that many patients with FL may never require treatment, with up to 20% of patients remaining treatment-free at 10 years. On the other hand, some patients have a course marked by less durable responses, frequent relapses, and increased mortality. A prospective, randomized study from Italy attempted to identify high-risk patients at diagnosis and randomized them to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles alone or an intensified chemotherapy regimen followed by autologous hematopoietic cell transplantation (auto-HCT). Although the auto-HCT arm was associated with improved 4-year event-free survival (61% vs 28%; P< .001), there was no difference in 4-year OS (81% vs 80%; P 5 .96). These results call into question the value of risk scores at diagnosis in stratifying patients with FL for more intensive treatment regimens. Subsequent analyses have identified early treatment failure (ETF) as a predictor of worse OS for patients with FL. The National LymphoCare Study (NLCS) prospectively followed newly diagnosed FL patients over a 10-year period of follow-up. Of the 588 patients in this study who received upfront therapy with R-CHOP, those who experienced progression of disease within 24 months of their initial therapy experienced inferior outcomes. Although only 110 of the 588 patients (19%) experienced early progression of disease, the 5-year OS rate in that group was inferior at 50% (95% confidence interval [CI], 39.4%-59.2%) in comparison with the rate of 90% (95% CI, 86.2%-92.4%) for the patients without early progression. This inferior outcome was maintained even when adjustments were made for the Follicular Lymphoma International Prognostic Index score at diagnosis (hazard ratio, 6.44; 95% CI, 4.33-9.58). A combined Mayo Clinic/University of Iowa/Lyon analysis independently validated these results, finding that patients who failed to remain event-free 12 months after chemoimmunotherapy had inferior OS independently of the Follicular Lymphoma International Prognostic Index score at diagnosis. Auto-HCT and allogeneic hematopoietic cell transplantation (allo-HCT) have been used in relapsed/refractory FL, but with the exception of a single Italian study of upfront auto-HCT consolidation, randomized, prospective data from the rituximab era are nonexistent. In the pre-rituximab era, the CUP trial randomized relapsed FL patients with at least a partial response (PR) to 3 cycles of salvage chemotherapy to 3 additional cycles of therapy or auto-HCT. There was a progression-free survival benefit to undergoing auto-HCT (P 5 .0037), with a trend toward an OS benefit (P 5 .079). A clinical trial in the rituximab era was designed to determine whether auto-HCT or allo-HCT was superior in this setting, but it was closed early because of poor accrual. Previous publications based on Center for International Blood and Marrow Transplant Research (CIBMTR) registry data have described long-term outcomes of auto-HCT and allo-HCT in the rituximab era for patients with relapsed/refractory FL. Both analyses found similar outcomes with either modality, with many patients in both groups deriving a long-term benefit despite higher rates of nonrelapse mortality (NRM) in allo-HCT recipients. In this issue of Cancer, Smith et al take the previous CIBMTR analyses one step further by examining the ETF population, which has been shown to have inferior long-term outcomes. The CIBMTR registry combines the experience of more than 500 transplant centers across the world by longitudinally following patients who have received any type of