甲氨蝶呤致化学性蛛网膜炎1例

病例患儿，女，11岁。2年半前被确诊为急性淋巴细胞白血病L2型，现回院化疗。用甲氨蝶呤12.5mg，地塞米松5mg，阿糖胞苷35mg，生理盐水5ml鞘内注射，2～3小时后患者出现头痛，呕吐，发热，最高体温达40．1℃，热退后症状缓解，查体颈项强直阳性，被确诊为化学性蛛网膜炎。     

鞘内注射药物治疗神经精神性红斑狼疮的临床研究

目的:探讨甲氨蝶呤联合地塞米松鞘内注射治疗神经精神性红斑狼疮的效果。方法:对64例行鞘内注射药物治疗的系统性红斑狼疮中枢神经系统损害患者治疗前后的临床表现、脑脊液、头颅CT或MRI进行分析。结果:64例中57例临床症状完全好转,脑脊液压力下降。结论:甲氨蝶呤联合地塞米松鞘内注射治疗神经精神性红斑狼疮有明显效果。     

探讨不同治疗方案对肺腺癌脑膜转移患者脑脊液癌胚抗原(CEA)下降率及预后的影响

目的探究肺腺癌脑膜转移患者采取不同治疗方案对脑脊液癌胚抗原下降率及预后的影响。方法此次80例研究对象筛选自2019年1月至2019年12月在本院进行治疗的肺腺癌脑膜转移患者,所有患者均基于甲氨蝶呤鞘内注射进行治疗,甲组仅采取甲氨蝶呤鞘内注射治疗,乙组采取甲氨蝶呤鞘内注射与血脑屏障药物联合治疗,丙组采取甲氨蝶呤鞘内注射与培美曲塞+贝伐珠单抗±铂类化疗联合治疗,丁组采取甲氨蝶呤鞘内注射与酪氨酸激酶抑制剂联合治疗,对比组间治疗效果。结果所有患者均完成甲氨蝶呤鞘内注射,累积剂量可达到120mg,随着升高甲氨蝶呤鞘内注射累积剂量(30mg、60mg、90mg、120mg),四组患者均升高脑脊液癌胚抗原下降率,组间差异显著(P<0.05);相同甲氨蝶呤累积剂量下,丙组患者癌胚抗原下降率升高程度高于甲组、乙组及丁组,且丁组癌胚抗原下降率升高程度高于甲组、乙组,差异显著(P<0.05)。结论肺腺癌脑膜转移患者采取甲氨蝶呤鞘内注射联合酪氨酸激酶抑制剂类分子靶向药物治疗,能够提升治疗有效率,延长患者生存期,值得临床应用实践。     

白血病治疗期用CSF作稀释液作鞘内注射

预防性头部照射和鞘内注射药物(氨甲喋呤和阿糖胞苷)能预防脑膜白血病的发生。鞘内滴注药物的部分并发症是由稀释液所引起。使用人工脊髓液能明显地降低发病率,但这种溶液难以制备。本文改用病人自己脊髓液稀释氨甲喋呤和阿糖胞苷作鞘内注射。方法是将脊髓针一次刺入,抽出液体作细胞计数和生化检验,另抽2～5ml于注射器内,与粉末状的化学治疗药物混匀,然后重新滴注。由于     

鞘内注射甲氨蝶呤治疗脑膜癌的疗效

目的 探讨鞘内注射甲氨蝶呤治疗脑膜癌的疗效、安全性和预后.方法 回顾性分析接受甲氨蝶呤鞘内注射化疗的22例脑膜癌患者的临床资料,分析鞘内注射化疗的疗效、不良反应及预后.结果 22例患者均接受鞘内注射化疗,14例(63.9％)头痛减轻,3例(13.6％)精神行为异常缓解;6例患者出现鞘内注射相关不良反应,其中神经根受刺激...     

鞘内注射预防和治疗中枢神经系统白血病的不良反应及其处理(附71例分析)

鞘内注射化疗药物是预防和治疗中枢神经系统白血病（CNSL）的主要方法之一，但有不少不良反应，有时甚至危及生命。我科自1989年以来共有71例CNSL患儿反复多次进行鞘内注射，其中60例患儿出现各种不良反应，本文分析了鞘内注射各种下良反应的临床表现、发病率、发病机理和处理方法。现报道如下。1材料与方法1．1一般资料：本组71例，男38例，女33例，年龄2～14岁，均经骨髓检查确诊为急性淋巴细胞性白血病。CNSL诊断按1976年南宁召开的全国白血病防治研究协作会议制定的诊断标准[1]。1．2治疗方法：30例单用甲氨喋呤（MTX）或阿糖胞苷…     

急性淋巴细胞白血病中枢神经系统病变的预防——两种方法的比较

本文报告1971年7月至1973年3月间194例儿童(年龄<15岁)急性淋巴细胞白血病(ALL)鞘内注药和颅脑照射预防中枢神经系统(CNS)白血病的研究结果。 CNS防治:以氨甲喋呤15mg/m~2(最大剂量为15mg),琥珀酰氢化考的松钠15mg/m~2和阿糖胞苷30mg/m~2溶于Elliott’s B溶液或生理盐水中,连续分别注入鞘内。在维持缓解的第1个月,给予每周1次鞘内注射。此后隔月1次,持续1年或至骨髓或CNS复发。近一半病例除鞘内注药外,再接受颅脑照射,在缓解开始时给予2,400rad,2岁以下儿童减为1,800rad。结果:119例ALL用VP方案诱导取得骨體缓解,     

鞘内注药化疗治疗中枢神经系统白血病的护理

目的 探讨鞘内注射化疗药物治疗中枢神经系统白血病的护理要点.方法 对43例中枢神经系统白血病患者进行化疗药物鞘内注射,并对护理要点进行总结.结果 用药后23例占53.49％的患者的症状得以显著改善、脑脊液检查也趋于正常.结论 对鞘内注射前后进行护理干预可避免患者不良反应的发生,或使其程度明显减轻.     

急性白血病病人鞘内注射化疗药物的护理干预

[目的]探讨责任护士全程陪同的护理干预对急性白血病病人鞘内注射化疗药不良反应的影响。[方法]初次行腰椎穿刺鞘内注射三联药（地塞米松、甲氨蝶呤、阿糖胞苷）的住院病人64例为研究对象,随机分为对照组、干预组各32例。对照组采用常规护理,干预组除常规护理外责任护士全程陪同进行综合护理干预,观察两组紧张、恐惧程度及不良反应发生情况;观察两组病人好转等程度及不良反应情况。[结果]两组病人的紧张、恐惧程度,头痛、头晕、恶心、呕吐不良反应比较差异有统计学意义（P〈0.05）。[结论]主管医生与责任护士密切配合,在鞘内注射全程中进行综合护理干预可减少病人紧张、恐惧的程度,减少不良反应发生率,有利于操作顺利完成。     

急性白血病病人鞘内注射化疗药物的护理干预

[目的]探讨责任护士全程陪同的护理干预对急性白血病病人鞘内注射化疗药不良反应的影响。[方法]初次行腰椎穿刺鞘内注射三联药(地塞米松、甲氨蝶呤、阿糖胞苷)的住院病人64例为研究对象,随机分为对照组、干预组各32例。对照组采用常规护理,干预组除常规护理外责任护士全程陪同进行综合护理干预,观察两组紧张、恐惧程度及不良反应发生情况;观察两组病人好转等程度及不良反应情况。[结果]两组病人的紧张、恐惧程度,头痛、头晕、恶心、呕吐不良反应比较差异有统计学意义(P0.05)。[结论]主管医生与责任护士密切配合,在鞘内注射全程中进行综合护理干预可减少病人紧张、恐惧的程度,减少不良反应发生率,有利于操作顺利完成。     

Effect of the intermittent prophylactic treatment of the central nervous system in adults with acute leukemia

Nineteen patients with acute leukemia, who achieved complete remission between January, 1980 and March, 1983, were given 10 mg of methotrexate (MTX) and 20 mg of prednisolone (PSL) intrathecally at 1st, 3rd, 6th, 10th and 15th month after the termination of consolidation therapy followed by the same dose twice a year, when the intensification therapy was being performed. During the observation period of 29 to 68 months, none developed central nervous system (CNS) leukemia. On the other hand, the incidence of CNS leukemia in patients given the prophylactic intrathecal treatment once or twice just after the complete remission was 35% (7/20) compared with 24% (8/33) in patients without treatment. No statistical difference was observed in these groups. The intrathecal administration of MTX and PSL is easy to perform and no adverse reaction was observed in our series. It is concluded that the intermittent prophylaxis with MTX and PSL is of benefit in preventing CNS leukemia in adults patients with acute leukemia.     

三氧化二砷和阿糖胞苷交替治疗急性早幼粒细胞性白血病的护理

目的 :总结三氧化二砷和阿糖胞苷交替治疗急性早幼粒细胞性白血病 (M3 )的护理经验。方法 :对 2 1例M3 患者进行三氧化二砷和阿糖胞苷交替治疗并采取有效的护理措施。结果 :2 1例M3 患者治疗总有效率95 2 4 % ,3年生存率 71 4 3% ,5年生存率 5 7 14 % ,生存质量明显提高。结论 :熟悉三氧化二砷和阿糖胞苷的药理作用、药物动力学特点及M3 病理生理特点 ,积极采取有针对性的护理措施有利于提高患者生存率和生存质量。     

Fentanyl inhibits acute myeloid leukemia differentiated cells and committed progenitors via opioid receptor‐independent suppression of Ras and STAT5 pathways

Fentanyl is a common sedative/analgesic used for intrathecal chemotherapy injection in children with acute leukemia. Given the contradictory findings that fentanyl has both inhibitory and stimulatory activities in cancer cells, we investigated the biological effects of fentanyl alone and its combination with standard of care in acute myeloid leukemia (AML) cells at all stages of development. We showed that fentanyl at clinically relevant concentration inhibited growth and colony formation of AML differentiated cells and committed progenitors without affecting their survival. Compared to AML cells without FLT3 mutation, cells harboring FLT3‐ITD mutation are likely to be more sensitive to fentanyl. However, fentanyl did not affect the most primitive AML stem cells. Fentanyl significantly augmented the efficacy of cytarabine but not midostaurin in AML differentiated cells and committed progenitors. We further demonstrated that fentanyl inhibited AML cells via suppressing Ras/Raf/MEK/ERK and STAT5 pathway, and this was not dependent on opioid receptor system. Our findings demonstrate the anti‐leukemia activity of fentanyl and synergistic effects between fentanyl and cytarabine in AML, via opioid receptor‐independent suppression of Ras and STAT5 pathways. Our work is the first to suggest the beneficial effects of fentanyl in children with leukemia.     

A case of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma in a Korean child

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) (intermediate DLBCL/BL), is a heterogeneous group with some features resembling DLBCL and others resembling BL. Here, we report a case of intermediate DLBCL/BL in a Korean child. A 2-yr-old male was admitted for evaluation and management of left hip pain. Immunohistochemistry of a biopsy of the femur neck revealed tumor cells positive for CD20, CD10, BCL2, BCL6, and Ki67. A bone marrow (BM) aspirate smear revealed that 49.3% of all nucleated cells were abnormal lymphoid cells, composed of large- and medium-sized cells. Immunophenotyping of the neoplastic cells revealed positivity for CD19, CD10, CD20, and sIg lambda and negativity for CD34, Tdt, and myeloperoxidase (MPO). Cytogenetic and FISH analyses showed a complex karyotype, including t(8;14)(q24.1;q32) and IGH-MYC fusion. Intensive chemotherapy was initiated, including prednisone, vincristine, L-asparaginase, daunorubicin, and central nervous system prophylaxis with intrathecal methotrexate (MTX) and cytarabine. One month after the initial diagnosis, BM examination revealed the persistent of abnormal lymphoid cells; cerebrospinal fluid cytology, including cytospin, showed atypical lymphoid cells. The patient was treated again with cyclophosphamide, vincristine, prednisone, adriamycin, MTX, and intrathecal MTX and cytarabine. The patient died of sepsis 5 months after the second round of chemotherapy.     

Clinical pharmacology of encapsulated sustained-release cytarabine

BACKGROUND: The therapeutic effectiveness of chemotherapy is often limited by the inability to sustain cytotoxic concentrations at the tumor site. Cytarabine liposome injection (DepoCyt), a sterile, injectable suspension of the antimetabolite cytarabine, encapsulated into multivesicular, lipid-based particles, has been developed to improve the treatment of neoplastic meningitis (NM) through sustained release of cytarabine. OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of intrathecal DepoCyt for the treatment of NM secondary to lymphoma or solid tumors. RESULTS: In preclinical and clinical studies, DepoCyt markedly extended the duration of tumor exposure to cytotoxic concentrations of cytarabine compared with administration of unbound cytarabine. Data from recent clinical studies demonstrate that DepoCyt improves complete response rates among patients with NM secondary to lymphoma. Trends in time to neurologic progression and median survival also favored DepoCyt over unbound cytarabine in these studies. Data have also been presented that suggest that patients with NM secondary to solid tumors benefit more from DepoCyt than from conventional treatment approaches. Chemical arachnoiditis (i.e., headache, fever, nausea, vomiting) was common in patients receiving DepoCyt, however, symptoms were manageable with oral dexamethasone. CONCLUSIONS: Encapsulation of cytarabine into liposomes for sustained release prolongs tumor exposure to cytotoxic concentrations of cytarabine, which may improve therapeutic efficacy in patients with NM secondary to lymphoma or solid tumors.     

成功治疗儿童罕见髓系/自然杀伤细胞祖细胞急性白血病1例

本文总结儿童髓系/自然杀伤细胞祖细胞急性白血病(M/NKPAL)的治疗经验以提高对该病的认识。对1例罕见的3岁8个月女童M/NKPAL合并中枢神经系统白血病进行了确诊分析,并对其治疗经过及长期随访结果进行了总结。结果表明,女童M/NKPAL合并中枢神经系统浸润得到了确诊,其免疫表型特征为CD7,CD33,CD34,CD56和HLA-DR共表达,MPO阴性,其他NK细胞和T、B细胞分化抗原阴性,染色体核型有+8和12p-。采用柔红霉素+阿糖胞苷化疗后达完全缓解,随后应用急性髓系白血病的化疗方案巩固强化治疗5个疗程,化疗方案中均含有大剂量阿糖胞苷,期间共行腰穿及鞘内注射治疗10次。停止治疗后中枢神经系统白血病复发,腰穿及鞘内注射治疗9次后行颅脑放疗36 Gy,取得了长期生存。结论:M/NKPAL是一种罕见的白血病,有特异的免疫表型特征,应用含有大剂量阿糖胞苷的急性髓系白血病化疗方案可能取得较好疗效。     

大剂量甲氨蝶呤治疗急性淋巴细胞白血病的观察及护理

目的探讨大剂量甲氨蝶呤（HDMTX）在急性淋巴细胞白血病（ALL）治疗中的疗效、不良反应及护理措施。方法对17例缓解期ALL患者进行23例次HDMTX（3．0g／m^2）连续24h静脉输注,同时给予三联鞘内注射。于第36h甲酰四氢叶酸钙（CF）解救,观察其不良反应并及时对症护理。结果全部患者均能耐受治疗,达持续完全缓解（CCR）。不良反应主要表现为恶心呕吐、口腔黏膜炎、中性粒细胞减少和一过性转氨酶升高等,经对症护理后,均于2周内恢复正常。结论HDMTX治疗ALL是一种安全可行的方法。其中化疗是根本,护理是关键,解救是契机。     

亚叶酸钙不同给药途径拮抗氨甲喋呤胃肠道反应的临床研究

目的:探讨亚叶酸钙不同给药途径拮抗氨甲喋呤胃肠道反应的效果.方法:将接受HDMTX加CF化疗的6例急性淋巴细胞性白血病患儿随机分为两组,观察组口服给药,对照组肌注给药,对比两组患儿的胃肠道反应.结果:观察组胃肠道反应明显轻于对照组(P＜0.05).结论:亚叶酸钙口服给药比注射给药能明显减轻氨甲喋呤的胃肠道反应.临床应用亚叶酸钙拮抗氨甲喋呤的毒副作用时,宜口服给药.     

Methotrexate cerebrospinal fluid and serum concentrations after intermediate-dose methotrexate infusion

Twenty-nine children with acute lymphocytic leukemia were given 24-hr infusions of intermediate-dose methotrexate (MTX, 1000 mg/m2) with and without intrathecal (IT) MTX (12 mg/m2), followed by leucovorin rescue. There was substantial interpatient variability in MTX systemic clearance (98.3 +/- 51 ml/min/m2), inducing total steady-state serum MTX concentrations ranging from 5.4 to 33.7 microM. The cerebrospinal fluid (CSF) concentration at the end of the infusion was 0.27 (+/- 0.1) microM when no IT-MTX was given and correlated with total steady-state (24-hr) serum concentration of MTX. By stepwise regression, the CSF MTX concentration correlated better with the nonprotein bound (free) steady-state serum MTX concentration (r = 0.66, P less than 0.01) than with total steady-state serum MTX concentration. Mean CSF: serum MTX concentration ratio was 0.023 (+/- 0.04) when no IT MTX was given. When an IT MTX dose (12 mg/m2) was given at the start of the MTX infusion, the steady-state CSF MTX concentration was 1.1 (+/- 0.4) microM, leading to a mean CSF: serum ratio of 0.073 (+/- 0.05). Despite 7-hydroxy-MTX serum concentrations exceeding MTX concentrations immediately after infusion, 7-hydroxy-MTX was not detectable in CSF of most patients (21 of 29), and was less than 50% of the concurrent MTX concentration when detectable. These data establish the substantial interpatient variability in CSF distribution of MTX after intermediate-dose MTX infusions and establish a significant correlation between steady-state free concentration of MTX in serum and CSF MTX concentration.     

Induction treatment of acute myeloid leukemia in an elderly patient with intramarrow injection/administration of cytarabine: first report of a case

We have used intramarrow injection/administration of cytarabine (Ara‐C) instead of conventional intravenous approach to induce remission in an elderly patient with acute myelogenous leukemia. We show for the first time that the intramarrow injection of chemotherapeutic agents such as Ara‐C can be used safely and effectively.