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Journal of Clinical Oncology, Vol 23, No 25 (September 1), 2005: pp. 6263-6264 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.01.5131
Should We Transplant Indolent Lymphoma?Oncology Specialists, S.C. Lutheran General Cancer Center, Park Ridge, IL To the Editor: In their recent report, the German Low Grade Lymphoma Study Group investigators conclude that the statistically significant increased risk of secondary hematologic malignancies after high-dose therapy and autologous stem-cell transplantation (ASCT) should not preclude clinicians from recommending such an approach to newly diagnosed patients with low-grade indolent non-Hodgkin's lymphoma (I-NHL).1 The authors should be commended on concluding this randomized study, but I find their final conclusion alarming and certainly worth discussing. The argument that improvement in progression-free survival (PFS) observed in this investigation outweighs the complications associated with ASCT is debatable. First, the value of ASCT in I-NHL is still nebulous. Many therapeutic interventions exist for these patients, and the disease is considered incurable. Although some studies suggested that ASCT might offer PFS advantage over conventional chemotherapy,2,3 the lack of an overall survival benefit precludes recommendation of this strategy as a front-line approach. Many reports have suggested that radioimmunotherapy (RIT) given initially or in relapsed patients would improve PFS.4,5 In fact, Kaminski et al5 recently reported a median PFS of 6.1 years in patients receiving 131I-Tositumomab as initial therapy, an outcome comparable to that reported by Lenz et al. Although some have reported secondary hematologic disorders after RIT, such risk remains negligible.6,7 In addition, many studies have incorporated chemoimmunotherapy by combining monoclonal antibodies, specifically rituximab, with alkylating agents or purine analogs, with results showing better response rates and improvement in PFS.8,9 Yet the risk of secondary malignancies in these studies was never increased. With the wide variety of therapeutic options in I-NHL, it may be ideal to reserve ASCT for the relapsed aggressive entity. Second, the authors fail to report on the criteria used to select patients for starting therapy. Although these were patients with advanced indolent lymphoma, their stage, by itself, is not an indication to institute ASCT or chemotherapy. This is important since disease characteristics ("B" symptoms, bulkiness, performance status, etc) have a proven impact on outcome. The recently identified Follicular Lymphoma International Prognostic Index (FLIPI) indicators suggest that subgroups of patients with poor clinical features may have an unfavorable prognosis.10 FLIPI was not available at the time when this trial was initiated. Yet, retrospective subgrouping of these patients according to FLIPI may identify a subgroup of patients who would benefit from ASCT. In these patients, the increased risk of secondary hematologic malignancies may be offset by a survival benefit. Finally, the authors did not provide information on the outcome of patients who progressed on interferon and were crossed over to the ASCT arm. The fact that these patients were able to undergo ASCT at progression without compromising their survival outcome argues against offering ASCT as a front-line therapy. Clinicians need to balance the risks versus the benefits of any treatment option, and although ASCT may be an attractive approach to the young patient with advanced stage disease, the statistically significant increased risk of secondary leukemic disorders in this and other studies, is worrisome. Given these risks, this approach should be reserved only for patients with aggressive and relapsed disease. Instead of advocating ASCT as front-line strategy, the data should have prompted the authors to conclude the opposite, especially in this era of targeted therapies, RIT, and molecular diagnostics. Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. REFERENCES
1. Lenz G, Dreyling M, Schienitz E, et al: Moderate increase of secondary hematologic malignancies after myeloablative radioimmunotherapy and autologous stem-cell transplantation in patients with indolent lymphoma: Results of a prospective randomized trial of the German Low Grade Lymphoma Study Group. J Clin Oncol 22:4926-4933, 2004
2. Schouten HC, Qian W, Kvaloy S, et al: High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: Results from the randomized European CUP trial. J Clin Oncol 21:3918-3927, 2003
3. Horning SJ, Negrin RS, Hoppe RT, et al: High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission: Results of a phase II clinical trial. Blood 97:404-409, 2001
4. Horning SJ, Younes A, Jain V, et al: Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol 23:712-719, 2005
5. Kaminski MS, Tuck M, Estes J, et al: 131I-Tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med 352:441-449, 2005 6. Nabhan C, Peterson LA, Kent S, et al: Secondary acute myelogenous leukemia with MLL gene rearrangement following radioimmunotherapy for non-Hodgkin's lymphoma. Leuk Lymphoma 43:2145-2149, 2002[CrossRef][Medline]
7. Kaminski MS, Estes J, Zasadny KR, et al: Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: Updated results and long-term follow-up of the University of Michigan experience. Blood 96:1259-1266, 2000
8. Czuczman MS, Koryzna A, Mohr A, et al: Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol 23:694-704, 2005
9. Marcus R, Imrie K, Belch A, et al: CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 105:1417-1423, 2005
10. Solal-Celigny P, Roy P, Colombat P, et al: Follicular lymphoma international prognostic index. Blood 104:1258-1265, 2004
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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