来自英国血液病委员会的成人原发性中枢神经系统淋巴瘤(PCNSL)和原发性眼内淋巴瘤(PIOL)治疗指南

治疗指南

1  原发性中枢神经系统淋巴瘤的诊断必须总是组织学水平的。当有疑似淋巴瘤出现后，立体定向活检是最适合的外科手段。在淋巴瘤的治疗过程中，外科手术切除没有任何用武之地。Biopsy samples for PCNSL and PIOL should be subjected to central pathological review在活检之前，切忌进行类固醇激素的给予(证据级别 C,推荐级别IV)。上海东方医院神经外科魏社鹏

2  疾病的分期包括胸部，腹部和盆腔的CT检查，老年病人的睾丸超声检查。腰穿脑脊液蛋白和葡萄糖定量检查，细胞学检查，流式细胞仪分析以及免疫球蛋白基因重组研究。眼部的检查包括前房，玻璃体和眼底。眼内疾病应当进行活检，所有病人都应该明确有无HIV感染(证据级别 C,推荐级别IV)。

3  预后评分的计算应当依赖于年龄大于60岁，体力状态大于1分，升高的乳酸脱氢酶，升高的脑脊液蛋白和脑深部实质受累(证据级别 C,推荐级别IV)。

4  在准备进行治疗之前，病人和家属都应该知道治疗有导致病人认知功能下降的危险(证据级别 C,推荐级别IV)。

5  地塞米松能够使病人达到短期缓解，但不可以在活检之前使用(证据级别 C,推荐级别IV)。

6  全脑放疗能够提供有效的缓解，但是不应该作为那些有足够体格接受化疗的病人的一线治疗方案(证据级别 B,推荐级别III)。

7  在原发性中枢神经系统淋巴瘤的化疗中，CHOP方案（环磷酰胺、阿霉素、长春新硷和强的松）没有作用(证据级别 A,推荐级别1b)。

8  如果身体足够好，所有的病人都应该将化疗作为第一线的治疗措施。化疗方案为大剂量甲氨蝶呤总共3-5次，每次给在2-3小时内给予每平方米3g以上的甲氨蝶呤。甲氨蝶呤的疗效可以被能穿透中枢神经系统的化疗药物如阿糖胞苷所增强。但是这种方案的实行应当有充实的草案作为根据或者在临床试验中给予(证据级别 B,推荐级别IIa)。

9  对使用以甲氨蝶呤为基础的化疗方案后出现完全缓解的病人应当给予巩固性的放疗。60岁以下的病人，除非在化疗之后已经出现认知障碍，一般都应该要追加全脑放疗。那些等于或者大于60岁的病人，认知功能的损害相比于放疗带来的潜在的好处还是很小的(证据级别 B,推荐级别IIa)。

10  没有证据支持在大剂量静脉内MTX化疗之外，进行鞘内化疗的会有额外的好处(证据级别 B,推荐级别III)。

11 大剂量化疗配合自体干细胞移植仍旧处于试验阶段，不推荐在临床试验之外使用(证据级别 B,推荐级别III)。

12  静脉内或者鞘内使用利妥昔单抗不作为原发性中枢神经系统淋巴瘤常规治疗方案，除非是在临床试验当中(证据级别 B,推荐级别III)。

13  在治疗原发性中枢神经系统淋巴瘤的过程中，使用药物进行血脑屏障的开放不建议施行，除非是在临床试验当中(证据级别 B,推荐级别IIb)。

14  复发或者难治性的疾病应当尝试进行补救性的全脑放疗。地塞米松应当被用于短期缓解使用。其它化疗方案例如替莫唑胺或者大剂量化疗配合自体干细胞移植在临床试验中已经展示了良好的前景，但仍旧需要进一步的临床试验(证据级别 B,推荐级别III)。

15  对眼球和中枢神经系统同时有淋巴瘤存在病人，应当给以大剂量甲氨蝶呤（HD-MTX）为基础的系统性化疗，继而对双侧眼球进行放疗。如果病人年龄小于60岁，还要对脑部进行放疗。孤立的眼部病变治疗方法同前。对于复发的局限于眼部的淋巴瘤病人，玻璃体内甲氨蝶呤治疗是个有效的治疗方法选择(证据级别 B,推荐级别III)。

 

Guidelines on the diagnosis and management of adult patients

with primary CNS lymphoma (PCNSL) and primary intra-ocular

lymphoma (PIOL)

British Committee for Standards in Haematology 

Summary of key recommendations

1. Diagnosis of PCNSL should always be confirmed histologically. When PCNSL is suspected, stereotactic biopsy is the preferred surgical procedure. Surgical resection has no role to play in the treatment of PCNSL. Biopsy samples for PCNSL and PIOL should be subjected to central pathological review. Every effort should be made to avoid corticosteroid therapy prior to biopsy (grade C, level IV).

2. Staging should include CT scanning of chest, abdomen and pelvis; testicular ultrasonography in elderly males; lumbar puncture for CSF protein/glucose quantification, cytology, flow cytometric analysis and immunoglobulin gene rearrangement studies; and examination of the anterior chamber of the eye, vitreous and ocular fundus. Intraocular lesions should be biopsied, and HIV infection should be confirmed or excluded in all patients (grade C, level IV).

3. A prognostic score should be calculated based upon age >60 years, performance status >1, raised LDH, raised CSF protein and involvement of deep brain matter (grade C, level IV)

4. Patients and relatives should be  warned of the risk of neurocognitive deterioration when consent for treatment is being obtained (grade C, level IV)

5. Dexamethasone is the treatment of choice for short-term palliation but should be avoided before biopsy (grade C, level IV)

6. Whole brain radiotherapy can provide effective palliation but should not be used as first-line therapy in patients who are sufficiently fit to receive chemotherapy (grade B, level III)

7. There is no role for CHOP-like chemotherapy in the treatment of primary CNS lymphoma (grade A, level 1b) 

8. All patients should be offered chemotherapy as first line treatment if they are sufficiently fit. Chemotherapy should consist of a regimen that includes HD-MTX (3-5 doses of   3g/m delivered over a maximum of 2-3 hours at intervals of not more than 2-3 weeks). The efficacy of HD-MTX may be improved by using it in combination with other CNS-penetrating chemotherapeutic agents such as cytarabine but such treatment should be based on established protocols and should ideally be given within the framework of a clinical trial (grade B, level IIa)

9. Consolidation WBRT should be considered in patients who achieve CR with MTX-based chemotherapy. In patients under 60 years of age, WBRT should be offered to patients unless there is a significant neurocognitive deficit following chemotherapy. In patients aged 60 years or over, neurocognitive side-effects are more likely to outweigh potential benefits (grade B, level IIa)

10. There is no evidence supporting a role for intrathecal chemotherapy as an adjunct to high-dose intravenous MTX in patients with PCNSL (grade B, level III) 

11.  First line treatment with high-dose chemotherapy and autologous stem cell transplantation remains experimental and should not be conducted outside clinical trials (grade B, level III):

12. Rituximab administered via the intrathecal or intraventricular route should not be used in the routine treatment of PCNSL except in a clinical trial (grade B, level III):

13. Pharmacological disruption of the blood-brain barrier should not be performed as part of the treatment of PCNSL unless as part of a clinical trial (grade B, level IIb):

14. Relapsed or refractory disease should be treated with salvage radiotherapy in patients who have not previously received WBRT. Dexamethasone should be considered for short-term palliation. Alternative chemotherapeutic regimens such as temozolomide or high-dose chemotherapy with autologous stem cell transplantation show promise but require further evaluation in clinical trials (grade B, level III)

15. Concurrent intraocular and CNS lymphoma should be treated with systemic HD-MTX-based chemotherapy followed by radiation to both globes and possibly also the brain if the patient is less than 60 years old. Isolated intraocular disease should be treated in the same way. Intravitreal MTX is an effective treatment option for patients with recurrent disease confined to the eyes (grade B, level III)