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. Allogeneic transplantation did not improve outcomes compared with rituximab-containing chemotherapy alone.
This retrospective cohort study included 172 patients aged 18 to 65 years with follicular lymphoma and subsequent biopsy-proven aggressive histology transformation. Patients undergoing transplant were those treated with autologous or allogeneic transplantation between 1994 and 2010 at transplant centers in Canada. A separate comparison group of patients receiving rituximab-containing chemotherapy alone was identified using the British Columbia Cancer Agency Centre for Lymphoid Cancer Database.
Patients with grades 1, 2, and 3A follicular lymphoma were included, and those with grade 3B lymphoma were excluded. Patients undergoing transplantation for a subsequent diagnosis of Hodgkin lymphoma or T-cell lymphoma and those without biopsy confirmation of transformation were excluded. All patients received at least one cycle of an anthracycline- or platinum-containing regimen with rituximab for transformation.
Of the 172 patients included in the analysis, 22 (13%) received allogeneic stem cell transplantation, 97 (56%) received autologous stem cell transplantation, and 53 (31%) received rituximab-containing chemotherapy alone (chemotherapy-alone group). Baseline characteristics and risk factors for outcomes were not balanced among groups.
At diagnosis, median ages were 44 years in the allogeneic transplant group, 51 years in the autologous transplant group, and 51 years in the chemotherapy-alone group (P = .001 overall); median ages at transformation were 48, 55, and 57 years, respectively (P < .001 overall), with 0%, 26%, and 36%, respectively, being 60 years or older (P = .005 overall). A total of 64%, 64%, and 51% of patients were male.
Patients in the allogeneic transplant group received a median of two systemic regimens for follicular lymphoma, and those in the other two groups received a median of one (P = .01 overall). Overall, 14% of patients receiving allogeneic transplant, 16% of those receiving autologous transplant, and 32% in the chemotherapy-alone group were chemotherapy-naive prior to transformation. Two patients in the allogeneic transplant group had received pretransformation autologous transplant. Other significant differences across groups included differences in year of diagnosis of transformation and proportions of patients receiving anthracyclines and platinums.
For patients undergoing stem cell transplantation, the median time from transformation to transplant was 6 to 8 months, although time varied widely from several months to several years. Patients in the autologous transplant group were significantly older at transplant than those in the allogeneic transplant group (median, 56 vs 48 years, P < .001) and were significantly more likely to have undergone transplant during 2006 to 2010 (75% vs 50%) compared with 2001 to 2005.
Overall, 77% of patients in the allogeneic transplant group and 85% of those in the autologous transplant group had chemosensitive disease. Approximately half of patients underwent transplant in first complete remission or partial remission and approximately one-third in second complete or partial remission.
Conditioning regimens included total-body irradiation in 55% of allogeneic transplant patients and 4% of autologous transplant patients (P < .001 overall). There was also a significant difference in stem cell sources, which included peripheral blood in 77% and 94% of patients, respectively, and bone marrow in 18% and 6%, respectively (P = .02 overall).
After a median follow-up of 7.5 years, 5-year overall survival from time of transformation was 46% in the allogeneic transplant group, 65% in the autologous transplant group, and 61% in the rituximab-containing chemotherapy–alone group (P = .24) and 5-year progression-free survival was 46%, 55%, and 40%, respectively (P = .12), with no significant differences observed across treatments. Similarly, there were no differences between the allogeneic transplant group and the autologous transplant group in 5-year post-transplant overall survival (45% and 57%, P = .12) or post-transplant progression-free survival (45% and 55%, P = .52).
Transplantation-related mortality rates were 23% in the allogeneic transplant group vs 4% in the autologous transplant group at 1 year (P = .01) and 23% vs 5% at 5 years (P = .001).
Survival Outcomes on Multivariate Analysis
Multivariate analysis was performed to adjust for the following factors: female sex, age less than 60 years at transformation, years from diagnosis of follicular lymphoma to transformation, advanced stage at transformation, elevated lactate dehydrogenase at transformation, number of chemotherapy regimens for transformation, anthracycline-containing chemotherapy, platinum-containing chemotherapy, and year of transformation of 2005 or later.
On multivariate analysis, patients in the autologous transplant group had significantly improved overall survival from the date of transformation compared with the rituximab-containing chemotherapy–alone group (hazard ratio [HR] = 0.13, P < .001), whereas there was no significant difference for the allogeneic transplant group vs the chemotherapy-alone group (HR = 0.44, P = .12). There was no significant difference for the allogeneic transplant group vs the autologous transplant group with regard to overall survival from time of transplant (HR = 1.5, P = .35). Progression-free survival from the date of transformation was significantly better in the autologous transplant group (HR = 0.09, P < .001) and in the allogeneic transplant group (HR = 0.19, P = .001) compared with the rituximab-containing chemotherapy–alone group.
As the authors noted, the study has a number of limitations due to its retrospective, nonrandomized cohort design, including the fact that multiple known and unknown factors led the study patients to be offered the treatments they received: “This likely generated selection bias, because a higher proportion of patients responding to chemotherapy would have proceeded to autologous [transplant] or allogeneic [transplant] rather than receive rituximab-containing chemotherapy only,” they wrote.
Patients in the chemotherapy-only group were also older than those in the transplant groups, which may have led to an overestimation of the benefit of stem cell transplantation.
The authors concluded:
[O]ur data suggest that eligible patients with transformed follicular lymphoma may benefit from autologous [stem cell transplantation] because it improves [overall survival] compared with rituximab-containing chemotherapy. However, the superiority of autologous [transplant] is modest. Patients with significant comorbidities related to organ dysfunction or age may be best served by treatment with rituximab-containing chemotherapy. Allogeneic [transplant] may be considered in certain circumstances, particularly if an autologous stem-cell graft cannot be collected or if better strategies emerge to minimize [transplantation-related mortality]. However, relapse and [transplantation-related mortality] remain significant problems in patients with transformation who undergo [stem cell transplantation], even in the rituximab era. Prospective trials will be required to demonstrate the optimal therapy for this aggressive form of non-Hodgkin lymphoma. ■
Disclosure: For full disclosures of the study authors, visit jco.ascopubs.org.
1. Villa D, Crump M, Panzarella T, et al: Autologous and allogeneic stem-cell transplantation for transformed follicular lymphoma: A report of the Canadian Blood and Marrow Transplant Group. J Clin Oncol 31:1164-1171, 2013.
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...