High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Relapsed or Refractory Primary CNS Lymphoma: A Retrospective Monocentric Analysis of Long-Term Outcome, Prognostic Factors, and Toxicity

Abstract

High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is reportedly an effective treatment strategy in relapsed or refractory primary CNS lymphoma (r/r PCNSL); however, only selected patients are eligible for this treatment. We retrospectively analyzed outcome, prognostic factors, and toxicity in 59 patients with r/r PCNSL planned to receive HCT-ASCT at our institution between January 2005 and December 2021 (n = 33 < 65 years; n = 26 ≥ 65 years). Median follow-up was 65 months (95% CI 21–109). Median age was 63 years (range 29–76), median Karnofsky performance score (KPS) was 80 (range 30–100). In the entire cohort of 59 patients, median overall survival (OS) was 14 months (95% CI 0–37). In 50/59 (84.7%) patients who completed HCT-ASCT, median progression free survival (PFS) was 12 months (95% CI 3–21) and median OS 30 months (95% CI 0–87). 1-year, 2-year, and 5-year OS rates of 61.2%, 52.3% and 47.1%, respectively, were observed. Six patients (10.2%) died related to treatment (1 during induction treatment, 5 post HCT-ASCT). Age was not prognostic. On univariate analysis, KPS ≥ 80 (p = 0.019) and complete or partial remission before HCT-ASCT (p = 0.026) were positive prognosticators of OS; on multivariate analysis, KPS (p = 0.043) and male gender (p = 0.039) had an impact on OS. The 5-year OS rate in patients with progressive or stable disease after induction treatment was 32.7%. In summary, HCT-ASCT was effective and feasible in this cohort of r/r PCNSL patients. Clinical state, remission status before HCT-ASCT, and gender influenced survival, whereas age did not influence outcome in this study.

Treatment Strategies and Prognostic Factors in Secondary Central Nervous System Lymphoma: A Multicenter Study of 124 Patients

“…Intriguingly, prolonged OS above 4 years was observed in every third patient in this challenging situation. This encouraging result confirms similar findings in PCNSL patients, recently published by our group 25 . Hence, HDT‐ASCT should be considered in initially refractory DLBCL‐SCNSL in clinical routine and future studies, at least until alternative treatments such as targeted therapy or immunotherapies (e.g.…”

“…This encouraging result confirms similar findings in PCNSL patients, recently published by our group. 25 Hence, HDT-ASCT should be considered in initially refractory DLBCL-SCNSL in clinical routine and future studies, at least until alternative treatments such as targeted therapy or immunotherapies (e.g. CAR-T cell therapy) prove to be superior.…”

Primary central nervous system lymphoma (PCNSL) in older patients

“…In this study, median PFS was 12 months and median OS was 30 months. HD-CT and ASCT is therefore an interesting therapeutic option for highly selected elderly patients [86 ▪▪ ].…”

High-dose chemotherapy and autologous stem cell transplantation in primary lymphomatoid granulomatosis of the central nervous system

“…Due to similarity of CNS-LG to primary CNS lymphomas (PCNSL), a reasonable rationale is to base the treatment on therapeutic advances of PCNSL. For diffuse large B-cell lymphoma (DLBCL) manifesting as CNS-lymphoma, HCT-ASCT has been well established as effective consolidation therapy with a clearly curative potential (Seidel et al 2022 ; Illerhaus et al 2016 ; Kasenda et al 2017 ). Current protocols usually consist of induction with rituximab and methotrexate (R-MTX; rituximab 375 mg/m 2 , MTX 4 g/m 2 ) and rituximab, thiotepa, and cytarabine (R-TT/AraC, rituximab 375 mg/m 2 , cytarabine 3000 mg/m 2 , thiotepa 40 mg/m 2 ), respectively.…”

“…Current protocols usually consist of induction with rituximab and methotrexate (R-MTX; rituximab 375 mg/m 2 , MTX 4 g/m 2 ) and rituximab, thiotepa, and cytarabine (R-TT/AraC, rituximab 375 mg/m 2 , cytarabine 3000 mg/m 2 , thiotepa 40 mg/m 2 ), respectively. Carmustine (BCNU), thiotepa, and rituximab (R-BCNU/TT; BCNU 400 mg/m 2 , thiotepa 10 mg/kg) followed by reinfusion of autologous hematopoietic cells is a feasible, effective, and often administered HCT protocol in this setting (Seidel et al 2022 ; Illerhaus et al 2016 ; Kasenda et al 2017 ).…”