The role of autologous hematopoietic cell transplantation (auto-HCT) in the management of indolent non-Hodgkin lymphomas (NHL) is shrouded in controversy. The outcomes of conventional therapies for many indolent lymphoma subtypes have dramatically improved over the last several years with the use of monoclonal antibodies, maintenance therapy programs and with the incorporation of radio-immunoconjugates. These significant advances in the armamentarium of lymphoma therapeutics warrant reappraisal of the current role of auto-HCT in the treatment algorithm of indolent NHL. Prospective randomized studies comparing contemporary chemoimmunotherapies against auto-HCT are lacking, leading to significant debate about the role and timing of auto-HCT for indolent NHL in the modern era. Although autografting for follicular lymphoma (FL) in first remission has been largely abandoned, it remains a useful modality for relapsed disease, especially for the subgroup of patients who are not candidates for allogeneic transplantation with a curative intent. Auto-HCT can provide durable disease control in chemosensitive transformed FL and mantle cell lymphoma (MCL) in first remission, with relatively low toxicity, and remains appropriate in chemoimmunotherapy era. Contemporary data are also reviewed to clarify the often underutilized role of autografting in relapsed MCL and other less frequent indolent NHL histologies. The biological basis of the increased risks of second malignancies with auto-HCT are reviewed to identify strategies designed to mitigate this risk by, for example, avoiding exposure to genotoxic agents, planning early stem cell collection/cryopreservation and minimizing the use of TBI with transplant conditioning, and so on. Genetic testing able to identify patients at high risk of therapy-related complications and novel post-transplant immune therapies with the potential of transforming autografting in indolent NHL from a remission-extending therapy to a curative modality are discussed to examine the possibly expanding role of auto-HCT for lymphoid malignancies in the coming years.
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