急性淋巴细胞白血病并中枢神经系统白血病的诊断与治疗

目的：探讨急性淋巴细胞白血病（ALL）并中枢神经系统白血病（CNSL）的诊断与治疗及影响发病和预后的因素。方法：对1990－1999年收治117例临床资料进行回顾分析。结果：CNSL发生距确诊ALL的中位数时间为8个月,高危型组发生率（54．85）明显高于标危型组（23．7％）。31例CNSL中以脑脊液（CSF）异常作出诊断远比临床症状多。CNSL治疗效果显示,大剂量氨甲喋呤＋三联鞘注＋四组（CR＋IT）相当。结论：为避免诊断假阳性造成的过度治疗,CSF仅有幼稚细胞而白细胞计数政党者诊断CNSL应慎重,HDMTX＋IT＋FC是治疗CNSL的有效措施。     

鞘内注射氨甲喋呤219例总结

鞘内注射氨甲喋呤（MTX）广泛用于白血病患儿的中枢神经系统白血病（CNSL）预防，但同时也可引起少数毒性反应，我科对1974年至1996年间住院的白血病患儿219例进行鞘内注射MTX1096人次所发生的毒性反应做了细致的观察，总结如下：临床资料住院患儿219例，其中男126例，占57．5％，女93例，占42．5％；年龄3个月－14岁；急性淋巴细胞白血病（ALL）111例，占50．7％；急性髓性白血病（AML）99例，占45．2％；淋巴肉瘤白血病9例，占4．1％。全部病例均经临床表现、血象、骨髓象而确诊，CNSL预防均采用单纯药物鞘注MTX每次10－12mg／m…     

小儿中枢神经系统白血病45例临床分析

本文报告了45例小儿中枢神经系统白血病（CNSL），分析了CNSL的隐匿性及二次复发，提出鞘内注射仍是预防和治疗CNSL的有效手段。主张在仅有脑脊液（CSF）检查发现1－2个幼稚细胞时，可观察1－2周再做CSF检查，以确定治疗方案。     

中枢神经系统白血病的早期诊断与治疗

本文对近三年来我院收治的３１例白血病儿ＣＮＳＬ发病及治疗情况进行了观察，在３１例白血病患儿中发生ＣＮＳＬ１６例，占白血病总数的５１．６％，其中ＡＬＬ１３例，ＡＭＬ３例，ＣＮＳＬ发生在初诊时或诱导缓解期１２例，占总数的７５％。我们使用我校自制的ＦＭＵ－５型细胞玻片离心沉淀器收集ＣＳＦ中细胞，其细胞收集率８０．５％，细胞完整率９９．９％，只需１０ｍｉｎ，临床使用方便、快速；本组１６例ＣＮＳＬ分别采用二     

脑脊液细胞学检查在中枢神经系统白血病中的应用

目的探讨脑脊液(CSF)细胞学检查在中枢神经系统白血病(CNSL)中的诊断价值。方法采用细胞离心涂片机收集CSF细胞,经染色镜检进行CSF细胞学检查。结果在59例白血病患儿438次CSF细胞学检查中,发现病例和标本阳性率分别为15.3%(9/59)和8.7%(38/438)。结论CSF细胞学检查对CNSL的早期诊断和疗效观察及复发判断有重要价值。     

“三联药”鞘注加静滴HD-MTX防治小儿中枢神经系统白血病363例疗效观察

尽管化学治疗迅速发展,但许多化疗药物不易透过血脑屏障,使中枢神经系统(CNS)成为白血病细胞的第一庇护所,中枢神经系统白血病(CNSL)成为急性淋巴细胞白血病(ALL)患儿复发的最重要原因。我们对1986～1996年收治的363例ALL患儿随访观察2年,结果表明:鞘注MTX、Ara-C、Dx加静滴HD-MTX可明显降低CNSL的发生率,对提高ALL患儿的持续完全缓解率(CCR)有着十分重要的意义;而且副作用少、安全可靠,适用于基层医疗单位开展。     

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目的通过对中枢神经系统白血病(CNSL)的防治,预防和降低白血病的髓外复发机会,提高儿童急性淋巴细胞性白血病(ALL)的长期生存。方法1999～2003年上海市新华医院对277例儿童ALL的诱导治疗期4～5次鞘内三联注射(甲氨蝶呤、阿糖胞苷、地塞米松),巩固期后采用大剂量甲氨蝶呤(HD-MTX)24h静脉连续滴注,进入维持后,每3个月1次,总共8～9次,以后改为鞘内注射3个月1次,直至化疗结束,对于超高危ALL患儿(白细胞计数>100×109/L、Ph1染色体阳性)采用头颅照射加鞘内注射。结果277例ALL患儿发生CNSL9例,发生率为3.2%,9例CNSL中4例骨髓复发,5例存活,中位生存时间22.2个月。结论CNSL的防治方法,明显降低了CNSL的发生率,使ALL患儿生存机会提高。发生CNSL的不利因素有高白细胞血症、T细胞性ALL、Ph1阳性染色体改变等。     

小儿中枢神经系统白血病45例临床分析

本文报告了 45例小儿中枢神经系统白血病 (CNSL) ,分析了CNSL的隐匿性及二次复发 ,提出鞘内注射仍是预防和治疗CNSL的有效手段。主张在仅有脑脊液 (CSF)检查发现 1～ 2个幼稚细胞时 ,可观察 1～ 2周再做CSF检查 ,以确定治疗方案     

儿童急性淋巴细胞性白血病中枢神经系统浸润的防治

目的通过对中枢神经系统白血病(CNSL)的防治,预防和降低白血病的髓外复发机会,提高儿童急性淋巴细胞性白血病(ALL)的长期生存。 方法1999~2003年上海市新华医院对277例儿童ALL的诱导治疗期4~5次鞘内三联注射(甲氨蝶呤、阿糖胞苷、地塞米松),巩固期后采用大剂量甲氨蝶呤(HD-MTX)24h静脉连续滴注,进入维持后,每3个月1次,总共8~9次,以后改为鞘内注射3个月1次,直至化疗结束,对于超高危ALL患儿(白细胞计数>100×10⁹/L、Ph1染色体阳性)采用头颅照射加鞘内注射。 结果277例ALL患儿发生CNSL 9例,发生率为3.2%,9例CNSL中4例骨髓复发,5例存活,中位生存时间22.2个月。 结论CNSL的防治方法,明显降低了CNSL的发生率,使ALL患儿生存机会提高。发生CNSL的不利因素有高白细胞血症、T细胞性ALL、Ph1阳性染色体改变等。     

大剂量MTX+鞘内注射对儿童中枢神经系统白血病的防治与中枢毒性

自1993年10月至1995年12月，对6O例儿童急性淋巴细胞性白血病（ALL）采用大剂量氨甲喋吟十鞘内注射十甲酰四氢叶酸钙解救（HDMTX＋IT十FC）方法预防髓外白血病，大大降低了中枢神经系统白血病的发生率6％）。但有1例患儿在第3次采取常规剂量和方法的HDMTX＋IT＋FC化疗时，出现严重的中枢神经毒性。一旦发生CNSL后，即使重新加强全身化疗、头颅放疗及HDMTX应用，仍出现高CNSL复发率和骨髓复发。结论：①HDMTX＋IT＋FC方法预防髓外白血病效果肯定，但应警惕中枢神经毒性的发生。②CNSL重在预防，一旦发生，疗效差，预后不良。     

不同剂量地塞米松治疗重症病毒性脑炎疗效观察

目的　 探讨不同剂量地塞米松 (DXM )治疗重症病毒性脑炎的疗效。 方法 　 5 6例重症病毒性脑炎患儿分为甲、乙两组 ,每组 2 8例。甲组采用短程大剂量DXM治疗 ,乙组采用短程小剂量DXM治疗 ,在治疗过程中对两组的临床疗效及药物副作用进行观察。 结果 　甲组的临床疗效明显优于乙组 (P <0 0 5 ) ,两组副作用基本相同 (P >0 0 5 )。 结论 　早期大剂量、短疗程DXM治疗重症病毒性脑炎安全、疗效好     

Early corticosteroid treatment does not affect severity of unconjugated hyperbilirubinemia in extreme low birth weight preterm infants

Aim: To determine the relationship between early postnatal dexamethasone (DXM) treatment and the severity of hyperbilirubinemia in extreme low birth weight (ELBW) preterm infants. Methods: In 54 ELBW preterm infants, total serum bilirubin concentrations (TSB) and phototherapy (PT) data during the first 10 days were evaluated retrospectively. ELBW infants had participated in a randomized controlled trial of early DXM treatment which aimed to assess effects on chronic lung disease. Infants had been treated with DXM (0.25 mg/kg twice daily at postnatal day 1 and 2) or with placebo (normal saline). Analysis was performed on an intention to treat basis. Results: Twenty‐five Infants had been randomized into the DXM group; 29 into the placebo group. Mean (±SD) TSB [120 (±19) μmol/L vs. 123 (±28) μmol/L, DXM versus placebo, respectively] and maximum TSB [178 (±23) μmol/L vs. 176 (±48), DXM versus placebo, respectively] concentrations were similar. TSB concentrations peaked 30 h earlier in the DXM group (p ≤ 0.05). The need for PT as well as the duration of PT was similar in both groups. Conclusions: Early DXM treatment does not affect the severity of neonatal hyperbilirubinemia in ELBW preterm infants. Our results seem compatible with the concept that factors other than bilirubin conjugation capacity are important for the pathophysiology of neonatal jaundice in ELBW preterm infants.     

Clinical Significance of Childhood Acute Myeloid Leukemias Expressing Lymphoid-Associated Antigens

The clinical significance of the expression of lymphoid-associated antigens in leukemic cells was studied in 66 children with newly diagnosed acute myeloid leukemia (AML). Among 66 AML cases, 17% were CD7-positive, 15% were CD19-positive, 8% were CD2-positive, and 5% were CD 10-positive. In 23 (35%) of the 66 AML cases, at least one lymphoid-associated antigen was expressed in the leukemic cells. When the clinical features and laboratory findings were compared at diagnosis between the 23 Ly⁺ and the 43 Ly^- AML cases, no statistically significant difference was found. The expression of CD34 was significantly more frequent in Ly⁺ AML cases (91%) than in Ly^- AML cases (31%). Chromosomal analysis revealed t(8;21) in 6 of the 21 Ly⁺ AML cases examined. No other specific chromosome abberation was noted. The 3-year event-free survival rates of Ly⁺ AML cases and Ly^- AML cases were 34%) ± 12% and 26% ± 8%, respectively. There was no statistically significant difference between the two groups. Further studies are required to determine the prognostic significance of lymphoid-associated antigen expression.     

Extramedullary Relapse in Childhood Leukemia

As long-term survival of children with leukemia is increasing, the prophylaxis of extramedullary leukemia has become a more important part of treatment. We studied the pattern of occurrence of extramedullary leukemia in a retrospective review. This review included a total of 2317 childhood leukemia patients aged 15 years or less who had been treated at 38 institutes in Japan between 1976 and 1985. Extramedullary leukemia developed in 386 of 1,724 ALL patients (22.4%) and 63 of 544 patients with ANLL (163%). Among the ALL patients, CNS-L was the most common form and was observed in 315 cases (81.6%), followed by testicular leukemia in 89 (23.0%). In the case of ANLL, the most common form of extramedullary leukemia was CNS-L (45 cases, 71.4%), followed by cutaneous leukemia in 10 cases (15.9%). In addition, leukemia of the lymph nodes, ovaries, bones, kidneys and eyes was observed in 7, 5, 5, 4 and 4 cases, respectively. The survival rate of ALL patients with CNS-L was 40.1% for isolated relapse and 2.7% for bone marrow relapse, and no more deaths occurred after 6 years from relapse. The survival rate of patients with testicular leukemia was 40.1% for isolated relapse and 5.9% for complicating bone marrow relapse, and no deaths occurred after 7 years from relapse. Cutaneous leukemia tended to occur late in older children with ALL and early in infants with ANLL, and all these patients died. Infiltration into the kidney was observed in 4 patients, all of whom died. More than 75% of patients died after isolated relapse of leukemia of the bones, ovaries, lymph nodes and eyes. Prophylactic extramedullary leukemia therapy, of CNS-L in particular, has played an important role in the treatment of childhood leukemia. Careful development of more effective therapy and close observation of late effects are required when monitoring affected children who are still growing.     

rhTPO联合大剂量地塞米松治疗儿童难治性免疫性血小板减少症的临床分析

目的 探讨重组人血小板生成素（rhTPO）联合大剂量地塞米松治疗儿童难治性免疫性血小板减少性紫癜（ITP）的疗效及安全性。方法 58例一线治疗无效的ITP患儿随机分为rhTPO治疗组（31例）和地塞米松治疗组（27例）。地塞米松组每28天静滴大剂量地塞米松4 d （每日0.6 mg/kg）,连续两个循环。rhTPO组在地塞米松治疗的基础上皮下注射rhTPO （每日300 U/kg）14 d。评价治疗第3、7、14天和第1、2、3个月末的总有效率（显效+有效）和治疗中的不良反应。结果 与DXM组相比,治疗第7天、14天、1个月,rhTPO联合治疗患儿的显效率、总有效率均较高（P < 0.05）;治疗第2个月,rhTPO联合治疗患儿仅总有效率较高（P < 0.05）。DXM组在治疗第一周发生肝损1例。两组患儿均未出现高血压、发热、皮疹、过敏反应、乏力等不良事件。结论 rhTPO联合大剂量地塞米松治疗难治性ITP的有效率高,而且安全。     

高剂量甲氨蝶呤排泄延迟解救措施的病例系列报告

背景：目前国内外对高剂量甲氨蝶呤（MTX）排泄延迟是否应该使用血液透析解救还存在争议。 目的：研究高通量血液透析（HF-HD）对肿瘤患儿MTX清除的有效性。 设计：病例系列报告。 方法：纳入2016年1月至2021年6月在上海交通大学医学院附属上海儿童医学中心血液肿瘤科行MTX化疗后44 h血药浓度＞10 μmol·L-1的连续病例,其中仅使用亚叶酸钙（CF）解救的患儿为非HF-HD组,使用HF-HD+CF解救的患儿为HF-HD组。比较2组患儿的胃肠道、肝功能、肾功能和血液系统毒性等指标。 主要结局指标：肝、肾功能不良反应发生率。 结果：20例发生20例次MTX延迟排泄,非HF-HD组9例,HF-HD组11例,两组患儿美国卫生及公共服务部常见不良事件评价标准v 4.0项目比较,CF组和HF-HD组肌酐、尿酸、ALT、AST、黏膜炎、24 h MTX浓度、MTX浓度恢复正常所需的时间差异均无统计学意义,两组患儿血液系统不良反应发生率差异无统计学意义（P＞0.05）;AST、ALT、发热、黏膜炎、WBC、NE、Hb、PLT异常发生率两组差异无统计学意义。 结论：肾功能正常的肿瘤患儿通过CF解救可有效安全清除MTX,非必要不选择透析。     

Sequential chemotherapy of advanced colorectal cancer with standard or high-dose methotrexate followed by 5-fluorouracil

Thirty patients with advanced measurable colorectal cancer were randomized to receive either methotrexate (MTX) 200 mg/m² or 40 mg/m², followed in four hours by 5-fluorouracil (5-FU) 600 mg/m². Patients receiving the higher dose MTX were given leucovorin rescue 24 hours later. Eight of 13 patients treated with 200 mg/m² MTX + 5-FU developed severe hematologic toxicity, leading to two toxic deaths. In addition, 9/13 developed mild azotemia, and three patients had severe gastrointestinal toxicity. No patients with prior chemotherapy responded to either regimen. Among those without prior chemotherapy, there were two of six and three of eight partial responses, respectively, in the 200 mg/m² and 40 mg/m² MTX regimens. Sequential 200 mg/m² MTX followed by 5-FU after four hours has unacceptable toxicity. Sequential treatment with standard dose MTX + 5-FU is tolerable and merits further study.     

High-dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude Total Therapy Study X

High-dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard-risk ALL: a leukocyte count less than 100 X 10(9)/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone-vincristine-asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow-up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P = .049) or historical institutional control regimens (P = .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.     

Ratio of methotrexate to folate uptake by lymphoblasts in children with B-lineage acute lymphoblastic leukemia: a pilot study

PURPOSE: Methotrexate (MTX) remains one of the most effective drugs for the treatment of children with acute lymphoblastic leukemia (ALL). Because MTX and 5-methyltetrahydrofolate (5CH3THF) share uptake and metabolic pathways, the efficacy of MTX is likely to depend not only on its metabolism but also on how well folate is accumulated by lymphoblasts. The authors' goal was to compare in vitro folate and antifolate uptake in B-lineage lymphoblasts from patients who remained in continuous complete remission (CCR) and those in whom relapse occurred. PATIENTS AND METHODS: Twenty-four children with B-lineage ALL were studied at diagnosis (n = 20) or relapse (n = 4). Lymphoblasts obtained by bone marrow aspiration were incubated for 24 hours in vitro with 0.05 microM 5CH3[3H]THF or 1 microM [3H]MTX. RESULTS: As of July 1999, 16 patients studied at diagnosis remained in CCR at a median follow-up of 45 months after achieving remission. Two of the patients studied at relapse are in second CCR; the remaining two died from progressive disease. The median uptake of neither [3H]MTX nor 5CH3[3H]THF differed significantly between the 16 patients in first CCR studied at diagnosis and the 4 patients studied at relapse. However, the median ratio of [3H]MTX:5CH3[3H]THF uptake differed significantly for patients who remained in first CCR versus patients studied at relapse. CONCLUSIONS: The uptake of [3H]MTX in relation to 5CH3[3H]THF by leukemic lymphoblasts in vitro may correlate positively with treatment outcome in children with B-lineage ALL. A larger study of homogeneously treated patients is necessary to confirm these results.     

儿童重症化脓性脑膜炎CD3＋ CD8＋ T细胞与炎症指标、体液免疫的变化

目的：通过观察儿童重症化脓性脑膜炎早期血CD3＋CD8＋T细胞的变化,以及与炎症指标、体液免疫指标之间的关系,探讨其在儿童重症化脓性脑膜炎发生发展中的临床意义。方法回顾性分析中国医科大学附属盛京医院PICU 2014年8月1日至2015年12月31日收治的39例1个月~14岁的重症化脓性脑膜炎患儿,血CD3＋CD8＋T细胞计数正常或升高(≥190个/mm3)为A组( n＝22),降低(<190个/mm3)为B组(n＝17),分析患儿的一般资料、血液炎症指标、体液免疫、脑脊液改变在两组患儿中的分布和差异。结果17例(43.6％)患儿CD3＋CD8＋T细胞明显下降;所有4例死亡均为B组患儿;虽然没有统计学差异,但 B 组 Glasgow 昏迷评分<8分者比例(58.8％)高于 A 组(31.8％)。B组C-反应蛋白、降钙素原中位数(最小值-最大值)分别为251.0(26.2-417.0)mg/L、32.7(0.9-100.0)ng/L,远远高于A组的106.5(12.0-458.0)mg/L、4.5(0.1-200.0)ng/L,差异有统计学意义(P<0.05);B组中6例(35.3％)外周血WBC<4×109/L,而 A组为1例(4.6％),中性粒细胞>80％的比例A组为7例(31.8％),而B组为12例(70.6％),两组比较差异有统计学意义(P<0.05)。 B组14例(82.3％)患儿脑脊液中糖含量<2.0 mmol/L,高于A组[11例(50.0％)],两组比较差异有统计学意义(P<0.05)。结论儿童重症化脓性脑膜炎CD3＋CD8＋T细胞可能受到抑制,其与患儿脑功能损伤程度、炎症反应以及预后相关。可能对指导临床免疫制剂的应用有一定帮助。