Patients in whom transformation occurs before therapy for the follicular lymphoma have a better outlook than when transformation occurs after extensive previous treatments for follicular lymphoma.
—James O. Armitage, MD
The place of either autologous or allogeneic hematopoietic stem cell transplantation in the care of patients with follicular lymphoma has been a point of controversy. However, for patients in whom an effective chemotherapy or chemoimmunotherapy regimen for low-grade follicular lymphoma fails, I believe that transplantation provides the best chance for prolonged failure-free survival.
Data on 121 patients from St. Bartholomew’s Hospital in London and the Dana-Farber Cancer Insitute in Boston,1 and the results for 126 patients treated at the University of Nebraska Medical Center (unpublished data), both show a 10-year freedom from relapse of lymphoma of approximately 45%. In addition, a European randomized trial showed improved failure-free and overall survival with autotransplant as part of the first salvage regimen.2 A recent report from a GELA/GOELAMS study found that rituximab (Rituxan) as part of primary therapy did not reduce the benefit of autologous transplantation after relapse.3 Allogeneic transplantation yields an even higher freedom from relapse, but has a higher treatment-related mortality and morbidity.4-6
Villa et al have addressed another issue in the use of autologous or allogeneic transplantation for patients with follicular lymphoma—ie, transplants for patients whose lymphoma has transformed from follicular to diffuse large B-cell lymphoma. In reviewing the data, it is important to remember that patients in whom transformation occurs before therapy for the follicular lymphoma have a better outlook than when transformation occurs after extensive previous treatments for follicular lymphoma. (In the Villa paper, patients in the chemotherapy-alone group were twice as likely to be chemotherapy-naive before transformation.)
The authors found a high treatment-related mortality rate associated with allogeneic transplantation (ie, 23% vs 5%) that reduced the chance that a presumed graft-vs-cancer effect in the allogeneic group might lead to a better outcome. Although the progression-free survival curves in the paper were not significantly different among patients undergoing transplant or treatment with chemotherapy and rituximab, many more late progressions in the chemotherapy-alone patients will likely lead, eventually, to a poorer overall survival unless these patients can be salvaged by a delayed transplant.
My experience has been that patients who present with a transformation to diffuse large B-cell lymphoma and have composite low-grade follicular lymphoma can often be “cured” of the high-grade lymphoma with regimens like CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, plus rituximab). However, for patients with transformation that occurs after previous treatment for follicular lymphoma, the results with further standard chemotherapy/chemoimmunotherapy have not been satisfactory, and these patients should be offered transplantation if they respond to salvage chemoimmunotherapy. The results by Villa and colleagues suggest that for most patients, autologous transplantation is likely to lead to the best outcome. ■
Dr. Armitage is Joe Shapiro Professor of Medicine and Professor and Chair of Oncology, University of Nebraska Medical School, Omaha.
Disclosure: Dr. Armitage is a consultant for Ziopharm, Seattle Genetics, GlaxoSmithKline, Spectrum, Genentech, and Roche; and is on the Board of Directors of Tesaro.
1. Rohatiner AZ, Nadler L, Davies AJ, et al: Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: Long-term follow-up. J Clin Oncol 25:2554-2559, 2007.
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. Le Gouill S, De Guibert S, Planche L, et al: Impact of the use of autologous stem cell transplantation at first relapse both in naive and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study. Haematologica 96:1128-1135, 2011.
4. van Besien K, Loberiza FR Jr, Bajorunaite R, et al: Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 102:3521-3529, 2003.
5. Robinson SP, Goldstone AH, Mackinnon S, et al: Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: An analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 100:4310-4316, 2002.
6. Peniket AJ, Ruiz de Elvira MC, Taghipour G, et al: An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: Allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant 31:667-678, 2003.
As reported by the Canadian Blood and Marrow Transplant Group in Journal of Clinical Oncology,1 patients with transformed follicular lymphoma receiving autologous transplantation have improved survival outcomes compared with patients receiving rituximab (Rituxan)-containing chemotherapy alone....