中枢神经系统原发淋巴瘤是一种较为难治的淋巴瘤,主要问题是大部分化疗药物无法突破血脑屏障,而传统的全脑照射和大剂量甲氨蝶蛉有较为严重的副作用。最近,在《血液》期刊登载的一篇文章介绍了一种新的疗法,取得了优异的治疗效果和相对较小的副作用。原文见附件,简介如下:
A New Treatment For Primary Central NervousSystem Lymphoma 中枢神经系统原发淋巴瘤的新疗法 Research sheds light on an effective newtreatment regimen for patients with what had once been considered a universallylethal disease. 对于曾经被认为普遍致命的疾病,研究展示了一种有效的新疗法。 Primary central nervous system lymphoma(PCNSL) is a rare non-Hodgkin'slymphoma subtype where the primary disease site is within thecentral nervous system. When the disease includes the brain, it is referred toas PCNSL with brain involvement. 中枢神经系统原发淋巴瘤(PCNSL )是一种罕见的非霍奇金淋巴瘤亚型,其主要病灶位于中枢神经系统。当病变部位包括脑部时,被称为中枢神经系统原发淋巴瘤脑侵犯。Untreated, PCNSL has been shown to bedeadly within three or four months of diagnosis. However, in the past 25 yearsthe disease has gone from beingunanimously deadly to being highly curable. 如果不治疗,PCNSL 可在确诊后三到四个月致命。但是,在过去的25 年中,这种疾病从普遍致命变成了有较高治愈率的疾病。The overwhelming majority of patientsdiagnosed with PCNSL have a disease that at the molecular level looks a lotlike diffuse large B-cell lymphoma (DLBCL). Unfortunately, when it came time totreat PCNSL, the conventional DLBCL therapy (R-CHOP) didn't work. Most expertsbelieve this is because PCNSL escapes chemo behind the blood-brain barrier,leading to relapse. 绝大多数PCNSL的病人在分子层面看上去像是弥漫大B淋巴瘤。不幸的事,当治疗PCNSL的时候,弥漫大B的常规方案(R-CHOP)没有作用。大多数专家认为PCNSL躲在血脑屏障后面,因此可以躲避化疗的作用而导致复发。 To prevent this, doctors beganadministering whole-brain radiotherapy (WBRT). While WBRT extended survival inpatients, it also led to lethal neurotoxicity in too many patients. When it wascombined with high-dose methotrexate-based chemotherapy, doctors found thatpatients who had been cured by the therapy were dying from the severe toxicity.为了防止这种情况发生,医生们开始采用全脑照射。全脑照射延长了病人的生存期,但是对很多病人也造成了致命的神经毒性。当与高剂量甲氨蝶蛉化疗联合的时候,很多被治愈的病人却因严重的治疗毒性而死亡。 Thus, while doctors knew that inductiontherapy for PCNSL patients would be methotrexate-based, the search was on forthe right consolidation therapy, one that could lead to long-term remission inpatients without being so devastatingly neurotoxic. 于是,医生们一方面认识到PCNSL的诱导方案应该是基于甲氨蝶蛉的,另一方面也开始寻找合适的巩固治疗方案,希望病人能够获得长期的缓解而避免严重的神经毒性。 Stunning New Findings 惊人的新发现 Researchers at Memorial Sloan KetteringCancer Center in New York, led by Antonio Omuro, may have found it. Theypublished the results of a single-center phase-2 study of newly diagnosedpatients with PCNSL that involves high-dose induction immunochemotherapy,followed by high-dose chemotherapy and an autologous stem-cell transplant as consolidationtherapy. This new regimen, although only tested in a relativelysmall sample, displayed an ability to overcome chemoresistance, get past theblood-brain barrier, and lead to durable remissions in this otherwisehard-to-treat patient population. 在纽约纪念斯隆-凯特琳癌症中心,由Antonio Omuro领导的研究人员可能发现了一种新疗法。他们公布了一项单中心二期临床试验的结果,这项研究接纳了新确诊的PCNSL的病人,采用高剂量的诱导免疫化疗,然后用高剂量化疗和自体干细胞移植进行巩固。尽管这个新的方案仅在相对较少的样本中进行了试验,但是却显示出了克服化疗耐药,突破血脑屏障的能力,使得这部分原本很难治疗的病人获得可持续的缓解。 In the study, published inthe journal Blood, patients received between five to cycles ofinduction immunochemotherapy involving the R-MPV regimen: 根据发表在《血液》期刊上的论文,在研究中,病人接受了5 -6 个周期的诱导免疫化疗,采用了R-MPV 方案: Rituximab美罗华 Methotrexate甲氨蝶蛉 Procarbazine甲基苄肼 Vincristine长春新碱 [Note: This regimen reflects the historicalsuccess of methotrexate against this subtype; the historical success ofmulti-drug therapy; and the fact that while rituximab doesn't as a rule crossthe blood-brain barrier in most patients, it appears to do so in patients withbrain lymphoma, when given in unusually high dosages.] 注:这个方案体现了用甲氨蝶蛉治疗这种亚型的成功历史;多药联合的成功历史;以及尽管美罗华在大多数情况下不能突破血脑屏障,但是在脑部淋巴瘤的病人中,如果给予超高剂量似乎有效的客观情况。 Patients with partial or complete responseto R-MPV continued on to consolidation high-dose chemotherapy (HDC) consistingof the TBC regimen, an aggressive regimen known to penetrate the centralnervous system: 对于R-MPV完全应答或部分应答的病人接下去用TBC方案的高剂量化疗进行巩固,这种激进的方案据悉可以突破血脑屏障: Thiotepa三胺硫磷 Busulfan白消安 Cyclophosphamide环磷酰胺 End Points 终点 Objective Response Rate 客观应答率 The objective response rate after R-MPVtherapy, meaning the percentage of patients who had either partial or completeresponse to the first round of chemotherapy, was 97 percent. R-MPV治疗后的客观应答率。即第一个周期的化疗后获得CR或PR的病人的百分比,为97%。 Progression-Free Survival Rate 无进展生存率 The two-year progression-free survival rateafter R-MPV therapy, meaning the percentage of patients who, after two years,showed no signs of their disease getting worse, was 79 percent. 在R-MPV后的两年无进展生存率,即在两年后没有疾病复发迹象的病人的百分比,为79%。 Overall Survival Rate总生存率 The two-year overall survival rate afterR-MPV therapy, meaning the percentage of patients who, after two years, arestill alive, was 81 percent. 在R-MPV后的两年总生存率,即在两年后依然存活的病人的百分比,为81%。 A total of 32 patients were involved in thestudy. 26 of them also underwent HDC and the stem cell transplant. In thesepatients, the two-year progression-free survival and overall survival rateswere 81 percent. This is significantly higher than any previous therapy andpotentially a tremendous breakthrough in the treatment of patients with thisdisease. 一共有32位病人参加了研究。其中26例进行了高剂量化疗和自体移植。在这些病人中,两年无进展生存率和总生存率位81%。这远高于先前任何治疗方案,对于这类病人来说可能是潜在的巨大突破。 Treatment-Related Questions治疗相关问题 The trial didn't go smoothly for everypatient. Specifically, there were three treatment-related deaths. 这个试验并不是对所有病人都顺利,有三例治疗相关的死亡。 However, researchers determined that forthe overwhelming majority of patients in the study, not only is this newtreatment highly effective, it also has an acceptable toxicity profile, anddoes not appear to be neurotoxic. 但是,研究人员确信,对于参加研究的绝大多数病人来说,这个新的疗法不仅高度有效,而且毒性可以接受,没有过分的神经毒性。 The team found that PCNSL as a disease,before any treatment, can by itself impair cognitive function. One concern isthat treatment can augment impairment so they included, as part of the study,prospective neuropsychological evaluations in the form of neuropsych tests,quality-of-life assessments, and radiographic evaluation of neurotoxicity. 研究发现PCNSL作为一种疾病,有可能本身影响认知能力。其中一个担心是怕治疗本身会加大这种认知能力的损害,因此,作为研究的一部分,也进行了前瞻性的神经心理评估,生活质量评估,和神经毒性的射线评估。 They reported that patients in this studywho experienced some cognitive impairment early on were no longer exhibitingany signs of impairment and were in fact gradually getting better. 他们报告说,在这项研究中,一些在初期经历了认知障碍的病人在治疗后不再有任何认知障碍的迹象,并且在逐渐好转。
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