Allogeneic Transplantation for Follicular Lymphoma: Does One Size Fit All?

Follicular lymphoma (FL) exhibits striking biologic and clinical heterogeneity. Patients with newly diagnosed asymptomatic or low-bulk disease may be observed or managed with immunotherapies alone. Chemoimmunotherapy is considered a standard treatment for patients with advanced, symptomatic disease. In patients with FL who achieve at least a partial remission after first-line chemoimmunotherapy, autologous (auto-) hematopoietic cell transplantation (HCT) consolidation is not recommended; however, most patients with FL experience disease relapse after frontline therapies, with the experience of therapy failure within 2 years of first-line treatments predicting poor survival. Despite remarkable efficacy, even in patients who experience failure with other therapies, auto-HCT and allogeneic (allo-) HCT remain underutilized in relapsed/refractory FL, even among healthy and younger patients. Early use of auto-HCT consolidation should be considered a standard therapy option for high-risk patients who experience early failure of chemoimmunotherapy (< 2 years). For patients with FL who experience failure of frontline therapies late (> 2 years), deferring auto-HCT until later in the disease course is reasonable. Allo-HCT is best reserved for medically fit individuals with heavily pretreated disease, persistent marrow involvement, refractory, but low-bulk, disease, and in those who experience a failure to mobilize stem cells for auto-HCT. Allo-HCT is also a reasonable option for patients with FL who experience failure with a prior autograft; lower-intensity conditioning regimens and HLA-matched related donors are preferred in that setting. Future research should focus on the eradication of minimal residual disease before HCT and the prevention of disease relapse after HCT by integrating novel targeted agents into pre-HCT and post-HCT regimens.