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Radioimmunotherapy for Stem Cell Transplantation in Non-Hodgkin's Lymphoma: In Pursuit of a Complete Response

^aHôpital Saint-Louis, Paris, France; ^bUniversity of Nebraska Medical Center, Omaha, Nebraska, USA; ^cCity of Hope National Medical Center, Duarte, California, USA; ^dIstituto Nazionale Tumori, Milan, Italy; ^eBMT & CBB, Chaim Sheba Medical Center, Tel Hashomer, Israel

Key Words. Stem cell transplantation • Lymphoma • Non-Hodgkin's lymphoma • Radioimmunotherapy • Iodine-131 tositumomab • Yttrium-90 ibritumomab tiuxetan

Correspondence: Christian Gisselbrecht, Ph.D., Hôpital Saint-Louis, Hémato-oncologie, 1 Avenue Claude Vellefaux, Paris 75010, France. Telephone: 33-1-4249-9296; Fax: 33-1-4249-9641; e-mail: christian.gisselbrecht{at}sls.ap-hop-paris.fr

Received March 27, 2009; accepted for publication June 1, 2009.

Disclosures: Christian Gisselbrecht: Research funding/contracted research: Bayer Schering Pharma; Julie Vose: Research funding/contracted research: GlaxoSmithKline, Biogen/IDEC; Auayporn Nademanee: None; Alessandro M. Gianni: None; Arnon Nagler: None.

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 independent peer reviewers.

High-dose chemotherapy (HDC) conditioning given in association with autologous stem cell transplantation (ASCT) or reduced-intensity conditioning (RIC) with allogeneic stem cell transplantation (alloSCT) are established treatment approaches for patients with chemotherapy-sensitive, relapsed, aggressive, or low-grade non-Hodgkin's lymphoma (NHL). These approaches have been shown to be the only curative option for patients with relapsed NHL. Despite data suggesting that prolonged event-free survival can be achieved with SCT combined with HDC, there are problems that may limit the utility of this approach for a broad patient population. For example, older patients, who make up the majority of the NHL population, may not be able to withstand the toxicities associated with this intensive regimen, and this therapy combination, especially when it includes the use of total-body irradiation, has been associated with a greater risk for secondary malignancies. Furthermore, relapse is the most common cause of treatment failure after HDC with ASCT and there is a poor success rate for those patients with either chemotherapy-refractory or heavily pretreated, multiple-relapsed disease. Consequently, there is an urgent need for other effective and well-tolerated approaches that will eradicate the residual disease that may persist before SCT, thus improving outcomes for patients with this life-threatening disease. In addition, approaches with better safety profiles would allow older patients to benefit from this therapeutic option. Because lymphomas are highly sensitive to radiation, radioimmunotherapy (RIT) has been used with great success in consolidation therapy and, as a result, there is great interest in exploring the use of RIT, either as a single agent or as augmentation of HDC, as part of a conditioning regimen for ASCT. The flexibility of including RIT as part of conditioning therapy also allows it to be combined with RIC to reduce the toxic effects of HDC. This treatment option replaces any concomitant loss of chemotherapy efficacy with a gain in RIT efficacy. The data so far suggest that the use of RIT in the autologous setting can improve clinical outcome with no added toxicity in these patients, whereas similar positive findings have been reported in preliminary studies of yttrium-90 ibritumomab tiuxetan combined with RIC and alloSCT in high-risk patients.

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