套细胞淋巴瘤患者CNS事件不会立即致命

阿姆斯特丹——澳大利亚Peter MacCallum癌症中心血液部主任John Seymour博士在欧洲血液病学会(EHA)年会上报告称，虽然套细胞淋巴瘤(MCL)是一种罕见疾病且患者预后往往不佳，但确诊时有中枢神经系统(CNS)受累的患者并非总是很快死亡。

根据多中心回顾性欧洲套细胞淋巴瘤协作网(EMCLN)研究结果，确诊时CNS事件粗患病率为0.9%，而累计患病率为4.1%。至CNS事件发生的中位时间为15.2个月，事件确认后总生存时间为3.9个月，但部分患者生存时间超过2年。研究者指出，我们现在对CNS事件患者的预后和结局有了更深入的了解。虽然CNS受累患者总体预后非常不良，但仍有部分患者情况相对较好。 能够接受大剂量阿糖胞苷或大剂量甲氨蝶呤治疗、年轻且身体状况较好的患者预后较好，部分患者可存活2年，因此CNS事件不一定导致患者快速死亡，并非意味着毫无希望。

John Seymour博士
 
MCL是一种罕见的非霍奇金淋巴瘤(NHL)，在美国NHL病例中只占不足3%，以老年患者为主(Cancer 2008;113:791-8)。CNS受累情况也非常罕见且往往具有致命性，但目前对其特点尚不完全了解，因此也不清楚CNS预防是否对患者有益。为此，EMCLN研究试图对该问题进行深入考察，确定CNS受累患病率，探索临床典型特征、治疗效果以及患者结局。

研究者查阅了12个中心确认的1,396例MCL患者的数据，其中1,339例患者无CNS受累。在57例CNS受累患者中，大部分(44例)发生在随访期间。确诊时发生CNS受累的患者中位年龄61岁，但年龄在38~82岁之间，以男性(70%)、IV期(91%)为主，28%的患者呈母细胞样组织学特征，单纯CNS受累患者15例。

患者突出特征为高MIPI(MCLy国际预后指数)计分(占61%)，69%的患者Ki-67>30%，β2-微球蛋白和乳酸脱氢酶增高者分别占77%和75%。骨髓和外周血为最常见结外受累部位，受累部位≥2个者占61%。CNS受累患者神经症状包括虚弱、精神状态改变以及复视等眼部症状。感觉障碍、疼痛、坐骨神经痛、头昏、眩晕、共济失调、癫痫以及吞咽困难等其他症状存在但不多见。脑脊液(CSF)细胞学和流式细胞术检查对于确认CNS受累具有高敏感性，85%的患者细胞学检查阳性，91%患者流式细胞术检查结果阳性。

患者在CNS受累之前接受了一系列化疗，但并非都有保护作用。化疗是缓解CNS疾病的最常见策略(67%)，部分患者的CNS疾病也的确得到完全缓解。在一项探索性分析中，这些患者与白细胞计数较低(<10.9×109/L)患者以及接受大剂量抗代谢药物的患者一样，总生存率也有改善趋势。

研究者称，从长远来看，上述数据为确定预测因素以及在事件发生之前确认高风险患者奠定了基础，并希望有助于预防措施的开展。

Seymour博士无相关利益冲突披露。

爱思唯尔  版权所有

By: SARA FREEMAN, Clinical Neurology News Digital Network

AMSTERDAM – Although it is rare and the prognosis for patients is often poor, the presence of central nervous system involvement at the time of diagnosis of mantle cell lymphoma is not always immediately fatal, according to findings from an international study.

According to the European Mantle Cell Lymphoma Network (EMCLN) findings, the crude prevalence of CNS events was 0.9% at the time of diagnosis and 4.1% at any time. The multicenter, retrospective study found that the median time to a CNS event’s occurring was 15.2 months, with an overall survival of 3.9 months after the event was identified, but some patients were still alive 2 years later.

"We now have some better descriptors about what the expectations and outcome of patients with central nervous system involvement are," Dr. John Seymour said in an interview at the annual congress of the European Hematology Association.

Dr. Seymour, professor and chair of the hematology service at Australia’s Peter MacCallum Cancer Centre in East Melbourne, Victoria, added that even though the overall prognosis of patients who develop CNS involvement is very poor, there are some patients who do better than others.

There is "a subgroup [of patients] who are able to receive high-dose ara-c [cytarabine] or high-dose methotrexate treatment, who are young and fit enough, who do somewhat better," Dr. Seymour said. "A proportion will be alive at 2 years, so it’s not an inevitably, rapidly fatal, and ... futile situation."

Mantle cell lymphomas are a rare type of non-Hodgkin’s lymphoma (NHL), accounting for just less than 3% of all NHL cases in the United States and affecting primarily more elderly patients (Cancer 2008;113:791-8).CNS involvement is also a rare and often devastating event, but it has not previously been very well characterized. As a result, it’s not known whether CNS prophylaxis is of benefit to patients.

The aim of the EMCLN study, therefore, was to look at the problem in more detail, to determine the prevalence of CNS involvement, and to look for any clinically defining features, effect of treatment, and patient outcomes.

A retrospective database review by EMCLN members in 12 centers identified 1,396 patients with mantle cell lymphoma, of whom 1,339 had no CNS involvement. Of the 57 patients with CNS involvement, most (44) developed it at some point during the course of their follow-up.

At diagnosis of mantle cell lymphoma, the patients who developed CNS involvement had a median age of 61 years, but this ranged from 38 years to 82 years; patients were predominantly men (70%), with stage IV (91%) disease, and 28% had blastoid histology. Isolated CNS involvement occurred in 15 cases.

Prominent features were a high MIPI (Mantle Cell Lymphoma International Prognostic Index) score (61% of cases), a Ki-67 greater than 30% in 69% of patients, and increased beta2-microglobulin and lactate dehydrogenase in 77% and 75% of cases, respectively. The bone marrow and the peripheral blood were the most common extranodal sites involved, affecting two or more sites in 61% of patients.

At diagnosis of CNS involvement, patients’ neurologic symptoms included weakness, altered mental state, headache, and ocular problems such as double vision. Other symptoms – such as sensory disturbances, pain, sciatica, dizziness, vertigo, ataxia, seizure, and dysphagia – occurred but were less frequent.

CSF cytology and flow cytometry showed a high sensitivity for identifying CNS involvement, with 85% having positive cytology and 91% a positive flow cytometry result.

"Patients had a range of chemotherapies prior to developing central nervous system involvement, but receipt of these regimens was not totally protective," Dr. Seymour said. Data were not collected to enable the relative risk of CNS development with the regimens received.

Chemotherapy was the most frequent treatment strategy to allay CNS disease (67%), and some patients did appear to achieve a complete remission of the CNS disease as a result. In an exploratory analysis, these patients also tended to have improved overall survival, as did those with lower white cell counts (less than 10.9 x 109/L), and who received treatment with high-dose antimetabolites.

"In the longer term, these data will provide a foundation for us to identify predictive factors, to identify – ahead of the event – those people at increased risk," Dr. Seymour said, adding his hope that this will allow preventive steps to be taken.

Dr. Seymour had no conflicts of interest.