Relapse after Autologous Stem Cell Transplant (ASCT) for Diffuse Large B Cell Lymphoma: Clinical Outcome and Prognostic Factors Affecting Long-Term Outcome

Introduction: We have evaluated the clinical outcome and the prognostic variables in patients with large B-cell non-Hodgkin’s lymphoma (DLBCL) who relapse after autologous stem cell transplantation (ASCT).

Methods. One hundred and two patients autografted for DLBCL [58 males (60%) and 44 (40%) females, median age of 49 (18–70) years] reported to the GEL/TAMO Cooperative Group between July 1993 and July 2007 who relapsed at a median time of 9 (range, 2–90) months after ASCT were included in this retrospective multicenter study. Inclusion criteria were to achieve at least a partial response (PR) after transplant and to receive treatment after relapse. After transplant 81 patients (79.4%) had achieved complete remission (CR), 11 (10.8%) uncertain CR, and 10 (9.8%) were partial responders. At relapse or progression, 65 patients (67%) had advanced clinical stage, 28.4% presented with B symptoms, 20 patients (15%) had age older than 60 and 13.8% with a bulky disease. Forty-seven percent of the patients had an age-adjusted IPI 2 or 3 and 52 (53.6%) and 25 (41%) had an elevated LDH or a high beta 2 microglobulin respectively. Regarding treatment at relapse or progression, forty-seven patients (46%) received rituximab, either alone (n=7) or in combination with chemotherapy (n=40), 44 received chemotherapy, 6 involved-field radiotherapy and the remaining 5 patients received a palliative treatment. Finally, 20 patients received a consolidation therapy with a second stem cell transplantation, (9 a second ASCT, and 11 an allogeneic transplant).

Results. Overall response (OR) rate was 54% (38.2% CR). Among the 47 patients who received rituximab-based protocols, the OR rate was 70.2% (48.9% CR). With a median follow-up after relapse/progression of 39.3 months (2.6 to 121.8) for surviving patients, the median overall survival (OS) from ASCT failure was 288 days with a median time to progression of 120 days. The actuarial 5-year OS and event-free survival (EFS) for the entire population of relapsed patients were 30.7% and 0%, respectively. Adverse prognostic factors significantly influencing OS and EFS in multivariate analyses were: haemoglobin level <100 g/l at salvage treatment (OS; relative risk (RR): 1.9, 95% CI 1.1–3.6, p=0.03); (EFS; RR 1.8, 95% CI 1.0–534, p=0.05), the IPI higher than 2 at progression (OS; RR: 2.3, 95% CI 1.3–4.0, p=0.003); (EFS; RR 1.8, 95% CI 1.1–3.0, p=0.028) and no achievement of response after relapse/progression (OS; RR: 17.4, 95% CI 7.8–39.0, p=0.000); (EFS; RR 5.8, 95% CI 2.9–11.5, p=0.000). The rituximab-based regimens as salvage treatment (RR: 2.0, 95% CI 1.1–3.6, p=0.02) was a significant favorable prognostic factor for OS in the multivariate analysis. In the same way, those lymphoma patients who underwent a second transplantation fared significantly better than patients who were not re-transplanted: 74.6% versus 27.5% (p=0.004) OS at 3 years and 12.5% versus 3.1% (p=0.05) EFS at 3 years.

Conclusion. Although prognosis of relapsed DLBCL after ASCT is generally poor, some patients with chemosensitive disease treated with rituximab-based regimens and/or a second autologous or allogeneic transplantation experienced prolonged survival. Given the limitations of this retrospective series, larger prospective studies are required in order to confirm the role and feasibility of these therapeutic approaches in these patients.