Salvage Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma

Introduction

Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma. This unique disease shows unsatisfactory outcomes comparing to other types of non-Hodgkin lymphoma and limited treatment options are available with relapsed or refractory disease. The purpose of this study is to evaluate outcomes of relapsed or refractory PCNSL patients treated with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT).

Methods

The registry data set of PCNSL, collected from March 1993 to May 2017 at a single institute, Asan Medical Center, was retrospectively reviewed and patients with refractory disease to first-line therapy and who relapsed were sorted. Among selected patients, patients who showed complete response (CR) or partial response (PR) to salvage therapy were enrolled in analyses and divided into two groups with whether high-dose chemotherapy followed-by ASCT was done or not as consolidation therapy. Overall survival (OS) was defined as the time from the day response was evaluated after salvage therapy to any cause of death, and progression free survival (PFS) was defined as the time from the day response was evaluated after salvage therapy to disease progression or any cause of death. Chi square test and Fisher's exact test was done to compare variables in two groups. Survival curves were estimated by Kaplan-Meier methods with log-rank tests and multivariate analysis with Cox-proportional hazards regression analyses was done to evaluate potential confounding effects of known prognostic factors. All statistical analyses were performed using IBM SPSS version 21.0.

Results

Total 241 patients with diagnosis of PCNSL were identified and 83 patients who had relapsed or refractory to induction chemotherapy were sorted. Among these patients, 39 patients who had CR or PR to salvage chemotherapy were enrolled in analyses. Median follow-up duration was 2.1 years (IQR 0.1-15.49), median OS was 1.5 years (95% CI 0.3-2.7), and median PFS was 1.4 years (95% CI 0.2-2.7). Median age was 63 years (range, 29-77), 69.2% of patients were 60 years or older and 59.0% of patients was male. Thirty patients (76.9%) had high-dose methotrexate based chemotherapy as first-line therapy and 71.8% had overall response (CR or PR). Twenty patients (48.7%) had ICE (ifosfamide, carboplatin, etoposide) + dexamethasone regimen, 22.9% had high-dose methotrexate based regimen. Thirty-one patients (79.5%) showed good performance (ECOG performance status < 2). Among these patients, 16 patients had high-dose chemotherapy followed-by ASCT as consolidation therapy and 23 patients did not. Proportion of patients with good performance status, salvage chemotherapy regimen, response to salvage therapy showed no statistically significant difference between two groups who had salvage ASCT or not. The median age was 55 years old (range 29-64) in salvage ASCT group, and 68 years old (range, 36-77) in non-ASCT. Median OS was 2.5 years [95% CI 0.3-4.6] in salvage ASCT group, and 1.0 years [95% CI 0.4-1.7] in group without salvage ASCT (p = 0.032). Median PFS was 1.5 years in salvage ASCT group, and 0.4 years [95% CI 0.4-0.5] in non-ASCT group (p = 0.027). In multivariate analyses with age, ECOG performance status, CSF protein level, and serum LD level, salvage ASCT revealed its independent prognostic impact for OS with HR of 0.11 [95% CI 0.01-0.96, p = 0.046], and for PFS with HR of 0.13 [95% CI 0.02-0.78, p = 0.025].

Conclusion

Consolidation therapy with high-dose chemotherapy followed-by ASCT could be a good treatment option in relapsed or refractory PCNSL patients who had response to salvage therapy. Prospective studies are needed to validate our results.