High-dose chemotherapy and autologous stem cell transplantation for primary central nervous system lymphoma: a multi-centre retrospective analysis from the United Kingdom

Abstract

The prognosis of patients with primary central nervous system lymphoma (PCNSL) has improved in recent years. This has partly been achieved by remission induction protocols incorporating high-dose methotrexate (HD-MTX) and rituximab. Given the high rates of relapse, consolidation therapy is usually considered in first response. Whole brain radiotherapy may prolong PFS but appears to confer no long-term survival advantage and is associated with significant neurocognitive dysfunction. Attempts to improve efficacy and reduce neurotoxicity of consolidation therapy have included thiotepa-based high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT). This multi-centre, retrospective study reports the outcome of 70 patients undergoing HDC-ASCT for PCNSL in the United Kingdom. The median age at diagnosis was 56 years and all patients received HD-MTX-containing induction regimens. All patients underwent HDC-ASCT in first response. The rate of complete response increased from 50% before HDC-ASCT to 77% following HDC-ASCT. Treatment-related mortality was 6%. At a median follow-up of 12 months from HDC-ASCT, the estimated 1- and 2-year PFS rates were 71.5% and overall survival 86.4% and 83.3%, respectively. These data are comparable to published studies of HDC-ASCT for PCNSL, supporting its feasibility and efficacy.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma

“…Long‐term survival rates, however, are lower in chemorefractory patients who fail to achieve partial remission to induction therapy (Soussain et al , ; Schorb et al , ). Survival outcomes from the prospective studies have been mirrored by a recently published ‘real world’ UK retrospective study (Kassam et al , ).…”

Primary central nervous system lymphoma: status and advances in diagnosis, molecular pathogenesis, and treatment

“…Several retrospective studies have reported the efficacy of HDC-ASCT as a first-line treatment for PCNSL. [ 49 , 50 ] The IELSG32 study, a random phase 3 study, assigned 122 patients (1:1) to WBRT (45 Gy) and thiotepa-based HDC/ASCT and reported 2-year PFS rates of 80% and 69%, respectively, without significant difference between groups; however, long-term neurotoxicity was noted in the WBRT group. [ 51 ] In 2019, the ANOCEF-GOELAMS randomized phase II PRECIS study evaluated the efficiency and toxicity of WBRT and ASCT as first-line treatment in 140 younger patients (<60 years) assigned to receive WBRT or ASCT as consolidation therapy, with a conditioning regimen comprising TBC and a WBRT dose of 40 Gy.…”

Consolidation Treatment for Primary Central Nervous System Lymphoma: Which Modality for Whom?

“…Table 1 describes those studies that reported on HDC/ ASCT of >30 patients. These studies include phase II studies, 2 phase II randomized studies, and several large retrospective studies [24,26,31,[44][45][46][47][48][49]. Overall high remission rates and excellent long-term outcomes have been reported with approximately a 2-year PFS of 75-87% and a 2-year OS of 66-93% with a treatment-related mortality (TRM) of 0-11.5%.…”