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Role of Hematopoietic Stem Cell Transplant in the Management of Follicular Lymphoma

University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA

Key Words. Lymphoma • Follicular lymphoma • Non-Hodgkin's • Hematopoietic stem cell transplantation • Transplantation conditioning • Bone marrow purging • Rituximab

Correspondence: Correspondence: Matthew Foster, M.D., Division of Hematology/Oncology, Department of Medicine, UNC, Chapel Hill, 3rd Floor Physicians Office Building, CB 7305, Chapel Hill, North Carolina 27599-7305, USA. Telephone: 919-966-5902; Fax: 919-966-6735; e-mail: mcfoster{at}med.unc.edu

Received March 10, 2009; accepted for publication May 8, 2009.

Disclosures: Matthew Foster: Consultant/advisory role: Genzyme; Don A. Gabriel: Intellectual property rights/inventor or patent holder: Patents provisionally filed; Honoraria: Speakers' bureau for Millennium, Novo Nordisk, Talecris; Research funding/contracted research: GlaxoSmithKline; Ownership interest: Invitrox; Thomas Shea: Consultant/advisory role: Board of Directors, CALGB; CIBMTR Scientific Advisors, president-elect; Honoraria: Speakers' bureau for Schering Plough, Genentech, Bristol-Myers Squibb, Novartis; Research funding/contracted research: Genzyme.

The article discusses unlabeled, investigational, or alternative use(s) of a product, device, or technique—alemtuzumab (Campath®; Genzyme), rituximab (Rituxan®; Genentech), iodine-131 tositumomab (Bexxar®; Corixa Corporation and GlaxoSmithKline), yttrium-90 ibritumomab tiuxetan (Zevalin®; Spectrum Pharmaceuticals, Inc.)—for conditioning regimens for HSCT.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors or independent peer reviewers.

Despite decades of published data regarding the application of autologous and allogeneic stem cell transplant in patients with follicular lymphoma, there remain no uniform indications for its use in this disease. Autologous transplant has been shown to lead to longer progression-free survival times in randomized trials when compared with postremission interferon-based chemoimmunotherapy. However, the development of rituximab and its use in frontline, salvage, and maintenance therapy complicates the decision to pursue autologous transplant, a modality developed prior to the advent of anti-CD20 monoclonal antibodies. Allogeneic transplant offers the advantages of lymphoma-free grafts and the immunologic graft-versus-lymphoma effect. These factors may confer the possibility of long-term remission, though historically they have been accompanied by high rates of upfront morbidity and mortality, especially in heavily pretreated patients with a poor performance status or chemotherapy-refractory disease. Advances in patient selection, human leukocyte antigen (HLA) matching, conditioning regimens, and supportive care have reduced transplant-related mortality and the incidence of graft-versus-host disease.

Recently published data focus on the incorporation of rituximab and radioimmunoconjugates prior to, during, and following autologous transplant. Furthermore, reduced-intensity allogeneic stem cell transplantation has increasingly been used for relapsed follicular lymphoma patients with comorbidities or advanced age. Several recent reports suggest that reduced-intensity regimens may provide a high likelihood of long-term disease-free survival for patients up to 70 years of age with a good performance status, chemotherapy-sensitive disease, and HLA-matched sibling donors. Such patients with relapsed disease should be referred to a transplant center that can enroll them in one of the forthcoming clinical trials that aim to confirm these outcomes.