High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation As a Salvage Treatment in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma

Introduction Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. There are only limited treatment options for patients with refractory disease to induction chemotherapy and patients with relapsed PCNSL. In this study, we evaluate high-dose chemotherapy followed by ASCT as a salvage treatment for patients with refractory or relapsed PCNSL to induction treatment.

Methods The PCNSL registry data prospectively collected from March 1993 to May 2017 at a single institute, Asan Medical Center, was retrospectively reviewed. Relapsed or refractory PCNSL patients who received high-dose chemotherapy followed by ASCT as salvage modality were included in this analyses. Overall survival (OS) was defined as the time from the day of stem cell infusion to death by any cause, and progression-free survival as the time from the day of stem cell infusion to disease progression or death by any cause.

Results Total 241 patients with diagnosis of PCNSL were identified and 18 patients were included in this study. Nine patients (50%) had refractory disease, 4 patients (22.2%) relapsed without consolidation, and 5 patients (27.8%) relapsed after whole-brain radiotherapy consolidation. Median follow-up period of the survivors was 2.2 years (range, 0.1-15.0). Median age was 57 years (range, 29-64) and 12 patients were male. Sixteen patients received methotrexate (MTX) based combination chemotherapy as induction treatment and 12 patients showed complete response (CR) or partial response (PR) as the best response to induction treatment. All patients received systemic chemotherapy as second-line treatment. Ten patients received ifosfamide, carboplatin, etoposide, and dexamethasone (ICE/D), 5 patients received cytarabine and etoposide (CYVE), 2 patients received high-dose MTX, and 1 patient received etoposide, dexamethasone, cytarabine, and cisplatin (EDAP). Four patients showed CR and 12 patients showed PR as the best response to second-line treatment. Twelve patients received thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimen for ASCT, 4 patients received BCNU, etoposide, cytarabine, and cyclophosphamide (BEAC), 1 patient received busulfan, cyclophosphamide, and etoposide (BuCyE), and 1 patient received BCNU, etoposide, cytarabine, and melphalan (BEAM). Median OS and PFS was 1.5 years (95% CI not applicable), and 0.9 years (95% CI 0.6-1.2), respectively. The 2-years OS and PFS rate was 49.5% and 36.7%, respectively. Median hospitalization duration was 19 days (range, 4-51) and median dose of CD34⁺ cells infused was 7.57 × 10⁶ cells/kg (range, 4.77-70.50). Seventeen patients (94.4%) had complete recovery of granulopoiesis and 15 patients (83.3%) had complete recovery of thrombopoiesis. Ten patients (55.6%) showed grade 3-4 diarrhea and 4 patients (22.2%) showed grade 3-4 mucositis.

Conclusion High-dose chemotherapy followed by ASCT could be a treatment option in patients with refractory or relapsed PCNSL to induction chemotherapy. Further prospective studies are warranted.