Aboulafia David M, Ratner Lee, Miles Steven A, Harrington William J
Divisions of Hematology and Oncology, Virginia Mason Medical Center and the University of Washington, Seattle, WA 9811, USA.
Clin Lymphoma Myeloma. 2006 Mar;6(5):399-402. doi: 10.3816/clm.2006.n.017.
A consistent association with Epstein-Barr Virus (EBV) distinguishes acquired immunodeficiency syndrome (AIDS)-related primary central nervous system lymphoma (PCNSL) from that which occurs in the general population. Recent descriptions of long-term remissions in patients with posttransplantation EBV-associated PCNSL who received EBV-specific therapy suggest some antitumor effect is anti-EBV mediated.
We enrolled 4 patients with AIDS-related PCNSL into a novel antiviral and immunomodulatory protocol. An additional patient was treated in a similar fashion off protocol. Treatment consisted of intravenously administered zidovudine (1.5 g twice daily), ganciclovir (5 mg/kg twice daily), and interleukin-2 (2,000,000 U twice daily). After 2 weeks of therapy, patients were switched to oral ganciclovir (1 g 3 times daily), patient-specific, highly active, antiretroviral therapy, and subcutaneous interleukin-2 (2,000,000 U 3 times weekly). A final patient was treated with intravenous zidovudine and hydroxyurea. All 6 patients had advanced-stage AIDS as reflected by a CD4+ T-lymphocyte cell count of < 50/microL and a detectable human immunodeficiency virus (HIV)-1 viral RNA load (median copies, 135,000/mL; range, 2170-360,000/mL). One of 4 protocol-enrolled patients remains in complete remission with > 4 years' follow-up.
Three patients died from complications of progressive PCNSL. Two patients treated off protocol exhibited favorable responses and remain in complete remission at 28 months and 52 months, respectively. Grade 3/4 myelosuppression was uniformly noted, but there were no clinically significant hemorrhagic or infectious complications.
We conclude that for patients with AIDS and PCNSL, treatments with dual efficacy against HIV and EBV merit further investigation. Our experience provides a platform for future studies.
与爱泼斯坦-巴尔病毒（EBV）的持续关联将获得性免疫缺陷综合征（AIDS）相关的原发性中枢神经系统淋巴瘤（PCNSL）与普通人群中发生的PCNSL区分开来。近期对接受EBV特异性治疗的移植后EBV相关PCNSL患者长期缓解的描述表明，某些抗肿瘤作用是由抗EBV介导的。
我们将4例AIDS相关PCNSL患者纳入一项新的抗病毒和免疫调节方案。另外1例患者在方案外以类似方式接受治疗。治疗包括静脉注射齐多夫定（每日2次，每次1.5 g）、更昔洛韦（每日2次，每次5 mg/kg）和白细胞介素-2（每日2次，每次2000000 U）。治疗2周后，患者改为口服更昔洛韦（每日3次，每次1 g）、患者特异性的高效抗逆转录病毒治疗以及皮下注射白细胞介素-2（每周3次，每次2000000 U）。最后1例患者接受静脉注射齐多夫定和羟基脲治疗。所有6例患者均处于晚期AIDS，表现为CD4 + T淋巴细胞计数<50/μL且可检测到人类免疫缺陷病毒（HIV）-1病毒RNA载量（中位数拷贝数，135000/mL；范围，2170 - 360000/mL）。4例纳入方案的患者中有1例在超过4年的随访后仍处于完全缓解状态。
3例患者死于进行性PCNSL的并发症。2例在方案外接受治疗的患者表现出良好反应，分别在28个月和52个月时仍处于完全缓解状态。均观察到3/4级骨髓抑制，但无临床显著的出血或感染并发症。
我们得出结论，对于患有AIDS和PCNSL的患者而言，对HIV和EBV具有双重疗效的治疗值得进一步研究。我们的经验为未来的研究提供了一个平台。
