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急性淋巴细胞白血病患儿在预防性中枢神经系统治疗期间(柏林方案)脑脊液蛋白质模式的变化

Changes of CSF-protein pattern in children with acute lymphoblastic leukemia during prophylactic CNS therapy (Berlin protocol).

作者信息

Siemes H, Rating D, Siegert M, Hanefeld F, Müller S, Gadner H, Riehm H

出版信息

Med Pediatr Oncol. 1980;8(1):25-34. doi: 10.1002/mpo.2950080105.

DOI:10.1002/mpo.2950080105
PMID:6934368
Abstract

The cerebral spinal fluid (CSF)-protein profiles of ten children with previously untreated acute lymphoblastic leukemia (ALL) were investigated by agarose gel electrophoresis. The profiles were determined at diagnosis and during the fifth to eighth week of treatment when preventive therapy for central nervous system (CNS) leukemia (skull irradiation, intrathecal methotrexate (ithMTX) was administered. The profiles were compared with those obtained from a control group of 67 children and those from 42 patients with acute aseptic meningitis. The data from the latter group demonstrated the CSF-protein pattern of partial blood-CSF barrier (B-CSF-B) breakdown. The children with ALL showed no or only minor signs of a B-CSF-B impairment at diagnosis and after four weeks of systemic treatment. However, CSF changes indicative of a lesion of the B-CSF-B increased in all children continuously during CNS prophylaxis. The protein profile at the end of combined chemotherapy and radiotherapy was very similar to that in patients with acute aseptic meningitis. These observations point to neurotoxic side effects on the CNS barrier system with the combination of cranial radiation and ithMTX. A striking finding was restricted heterogeneity of gamma-globulin, observed in the CSF of nine out of the ten children with ALL before or during treatment. The significance of this abnormality is unknown.

摘要

通过琼脂糖凝胶电泳对10例未经治疗的急性淋巴细胞白血病(ALL)患儿的脑脊液(CSF)蛋白质谱进行了研究。这些蛋白质谱在诊断时以及治疗的第五至八周期间确定,此时对中枢神经系统(CNS)白血病进行预防性治疗(颅骨照射、鞘内注射甲氨蝶呤(ithMTX))。将这些蛋白质谱与67名儿童的对照组以及42名急性无菌性脑膜炎患者的蛋白质谱进行了比较。后一组的数据显示了部分血脑屏障(B-CSF-B)破坏的脑脊液蛋白质模式。ALL患儿在诊断时和全身治疗四周后未显示或仅显示轻微的B-CSF-B损伤迹象。然而,在CNS预防期间,所有儿童中提示B-CSF-B损伤的脑脊液变化持续增加。联合化疗和放疗结束时的蛋白质谱与急性无菌性脑膜炎患者的蛋白质谱非常相似。这些观察结果表明,颅骨照射和ithMTX联合使用对CNS屏障系统有神经毒性副作用。一个显著的发现是,在10例ALL患儿中,有9例在治疗前或治疗期间脑脊液中观察到γ-球蛋白的异质性受限。这种异常的意义尚不清楚。

相似文献

1
Changes of CSF-protein pattern in children with acute lymphoblastic leukemia during prophylactic CNS therapy (Berlin protocol).急性淋巴细胞白血病患儿在预防性中枢神经系统治疗期间(柏林方案)脑脊液蛋白质模式的变化
Med Pediatr Oncol. 1980;8(1):25-34. doi: 10.1002/mpo.2950080105.
2
Acute changes in blood-CSF barrier permselectivity to serum proteins after intrathecal methotrexate and CNS irradiation.鞘内注射甲氨蝶呤和中枢神经系统照射后血脑脊液屏障对血清蛋白的通透选择性急性变化。
J Neurol. 1985;231(6):336-9. doi: 10.1007/BF00313712.
3
Studies on the assessment of neurotoxicity in children with acute lymphoblastic leukemia.
Cancer. 1987 Mar 1;59(5):891-5. doi: 10.1002/1097-0142(19870301)59:5<891::aid-cncr2820590506>3.0.co;2-m.
4
Prophylactic CNS therapy in childhood acute leukemia: review of methods used.
Am J Pediatr Hematol Oncol. 1979 Summer;1(2):119-26.
5
[Side effects and late results of the combined radio- and chemotherapy of the brain in children with acute lymphoblastic leukemia (author's transl)].
Strahlentherapie. 1979 Mar;155(3):165-70.
6
[Central nervous system irradiation for children with leukemia].
Gan No Rinsho. 1984 Feb;30(2):152-6.
7
Chemotherapy of acute lymphoblastic leukemia in children.
Am J Hematol. 1976;1(2):201-9. doi: 10.1002/ajh.2830010204.
8
[Prophylactic central nervous system irradiation for childhood acute lymphoblastic leukemia].
Gan No Rinsho. 1984 Apr;30(4):363-7.
9
Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica.鞘内注射甲氨蝶呤可替代颅脑照射,用于预防接受基于柏林-法兰克福-明斯特方案的强化化疗的中危急性淋巴细胞白血病患儿的中枢神经系统复发。意大利儿科血液学和肿瘤学协会。
J Clin Oncol. 1995 Oct;13(10):2497-502. doi: 10.1200/JCO.1995.13.10.2497.
10
Low numbers of CSF blasts at diagnosis do not predict for the development of CNS leukemia in children with intermediate-risk acute lymphoblastic leukemia: a Childrens Cancer Group report.诊断时脑脊液原始细胞数量少不能预测中危急性淋巴细胞白血病患儿中枢神经系统白血病的发生:儿童癌症研究组报告
J Clin Oncol. 1994 Dec;12(12):2594-600. doi: 10.1200/JCO.1994.12.12.2594.

引用本文的文献

1
Acute changes in blood-CSF barrier permselectivity to serum proteins after intrathecal methotrexate and CNS irradiation.鞘内注射甲氨蝶呤和中枢神经系统照射后血脑脊液屏障对血清蛋白的通透选择性急性变化。
J Neurol. 1985;231(6):336-9. doi: 10.1007/BF00313712.
2
[Changes in the blood-cerebrospinal fluid barrier for serum proteins in children with acute lymphatic leukemia].[急性淋巴细胞白血病患儿血清蛋白的血脑脊液屏障变化]
Klin Wochenschr. 1987 Jan 15;65(2):76-81. doi: 10.1007/BF01745478.