Clinical outcomes according to conditioning regimens in patients with primary central nervous system lymphoma undergoing consolidation autologous stem cell transplantation = 원발 중추신경계 림프종 환자의 자가조혈모세포이식 공고요법에서 고용량 화학요법 요법에 따른 임상 성적 분석

다국어 초록 (Multilingual Abstract)

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive extra- nodal non-Hodgkin lymphoma confined to the central nervous system or eyes. Recent pivotal randomized controlled trials have established high-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) as the preferred consolidation strategy, demonstrating improved survival and reduced neurotoxicity compared to whole brain radiotherapy. Among conditioning regimens, thiotepa-based approaches have shown superior efficacy, but optimal regimen selection among those thiotepa-containing ones remains unclear. This study compared clinical outcomes of consolidation ASCT according to conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), busulfan/thiotepa (BuTT), and non-thiotepa regimens. Methods: This retrospective study included 160 newly diagnosed PCNSL patients treated at Asan Medical Center from 2000 to 2023 who responded to HD-MTX-based induction chemotherapy and proceeded to consolidation ASCT. Patients were categorized by conditioning regimen: non-thiotepa (busulfan/cytarabine/etoposide [BuCyE], busulfan/melphalan/etoposide [BuMelE], or BCNU/etoposide/cytarabine/melphalan [BEAM]; n = 28), TBC (n = 71), and BuTT (n = 61). We evaluated progression-free survival (PFS), overall survival (OS), non-relapse mortality (NRM), and treatment-related toxicities. PFS was defined as the time from initiation of the conditioning to the date of disease progression or death from any cause, whichever occurred first. OS was defined as the time from initiation of the conditioning to the date of death from any cause. Results: The median age at diagnosis was 57 years (range 17–68), and 84 (52.5%) were male. The BuTT group was older than the TBC and non-thiotepa groups (median age: 60 vs. 54 vs. 55 years, respectively; p <0.001). With a median follow-up of 6.5 years, BuTT and TBC showed comparable outcomes (3-year PFS: 83.6% vs 80.3%, p = 0.221; 3-year OS: 86.7% vs 83.1%, p = 0.531), while non-thiotepa conditioning was significantly associated with worse survival outcomes with 3-year PFS rate of 46.4% (p <0.001) and 3-year OS rate of 64.3% (p = 0.008) compared with BuTT. One-year NRM was higher in patients receiving thiotepa-based regimens (BuTT 9.8% vs. TBC 7.0% vs. non-thiotepa 0%). TBC was more frequently associated with infections: grade ≥3 infections (TBC 45.7% vs. BuTT 34.4% vs. non-thiotepa 28.6%), bacteremia (21.1% vs. 13.1% vs. 3.6%), and septic shock (12.7% vs 6.6% vs 0%). In the multivariate analysis, there was no significant difference in survival outcomes of BuTT compared with TBC (PFS: hazard ratio [HR] 1.96, p = 0.150; OS: HR 3.02, p = 0.071), while non-thiotepa showed worse outcomes compared with BuTT (PFS: HR 5.60, p = 0.003; OS: HR 7.54, p = 0.005). In the elderly subgroup (age ≥60; BuTT n = 33, TBC n = 23), BuTT showed a trend toward better survival outcomes compared with TBC (3-year PFS: 78.8% vs 65.2%, p = 0.201; 3-year OS: 81.6% vs 69.6%, p = 0.330) and was associated with a significantly lower infection rate (39.4% vs 72.7%, p = 0.027). Conclusion: Thiotepa-based conditioning regimens were associated with superior survival compared to non-thiotepa regimens. While BuTT and TBC showed comparable survival outcomes, TBC was associated with a higher incidence of infections. Among patients aged ≥60 years, BuTT demonstrated lower infection rates and a favorable survival trend compared to TBC. These findings suggest that BuTT may represent a more optimal conditioning regimen, particularly for elderly PCNSL patients. Keywords: Primary central nervous system lymphoma, consolidation, autologous stem cell transplantation

목차 (Table of Contents)

• Summary i
• List of tables iv
• List of figures v
• Introduction 1
• Methods 3
• Results 6
• Discussion 23
• Conclusion 27
• References 28
• Korean summary 31