Zayac Adam S, Evens Andrew M, Danilov Alexey, Smith Stephen D, Jagadeesh Deepa, Leslie Lori A, Wei Catherine, Kim Seo-Hyun, Naik Seema, Sundaram Suchitra, Reddy Nishitha, Farooq Umar, Kenkre Vaishalee P, Epperla Narendranath, Blum Kristie A, Khan Nadia, Singh Daulath, Alderuccio Juan P, Godara Amandeep, Yazdy Maryam Sarraf, Diefenbach Catherine, Rabinovich Emma, Varma Gaurav, Karmali Reem, Shao Yusra, Trabolsi Asaad, Burkart Madelyn, Martin Peter, Stettner Sarah, Chauhan Ayushi, Choi Yun Kyong, Straker-Edwards Allandria, Klein Andreas, Churnetski Michael C, Boughan Kirsten M, Berg Stephanie, Haverkos Bradley M, Orellana-Noia Victor M, D'Angelo Christopher, Bond David A, Maliske Seth M, Vaca Ryan, Magarelli Gabriella, Sperling Amy, Gordon Max J, David Kevin A, Savani Malvi, Caimi Paolo, Kamdar Manali, Lunning Matthew A, Palmisiano Neil, Venugopal Parameswaran, Portell Craig A, Bachanova Veronika, Phillips Tycel, Lossos Izidore S, Olszewski Adam J
Lifespan Cancer Institute, Alpert Medical School of Brown University, Providence, RI.
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson University Hospital, New Brunswick, NJ.
Haematologica. 2021 Jul 1;106(7):1932-1942. doi: 10.3324/haematol.2020.270876.
Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.
中枢神经系统（CNS）受累于伯基特淋巴瘤（BL）构成了一项重大的治疗挑战，而当代治疗方案治疗CNS受累的相对能力仍不确定。我们利用2009年至2018年间美国30家机构诊断的成年BL患者的真实世界临床病理数据，描述了CNS受累的预后意义以及当代免疫化疗后CNS复发/进展的发生率。我们研究了基线CNS受累、患者特征、完全缓解（CR）率和生存率之间的关联。我们还研究了CNS复发的危险因素。19%（120/641）的患者（年龄18 - 88岁）有CNS受累。它与HIV感染、体能状态差、≥2个结外部位受累或骨髓受累独立相关。一线治疗方案的选择不受CNS受累的影响（P = 0.93）。有CNS疾病的患者CR率显著较低（59%对比无CNS疾病者的77%；P < 0.001），3年无进展生存率更差（调整后风险比[aHR]，1.53，95%置信区间[CI]，1.14 - 2.06，P = 0.004）以及总生存率更差（aHR，1.62，95%CI，1.18 - 2.22，P = 0.003）。CNS复发的3年累积发生率为6%（95%CI，4 - 8%）。与DA - EPOCH - R方案（13%）相比，接受其他方案（CODOX - M/IVAC，4%，或hyperCVAD/MA，3%）的患者中CNS复发率显著更低（调整后亚风险比，4.38，95%CI，2.16 - 8.87，P < 0.001）。BL患者的基线CNS受累相对常见，且预示着较差的预后，与一线治疗方案的选择无关。在实际临床实践中，使用具有高CNS渗透性的静脉全身药物的方案与较低的CNS复发风险相关。这一发现可能受到观察到的对DA - EPOCH - R方案中严格的CNS分期和鞘内治疗程序依从性欠佳的影响。
