多发性骨髓瘤移植治疗的现状

多发性骨髓瘤（MM）是浆细胞的恶性疾病占血液系统肿瘤的10％，生存期从几个月到大于10年。MM可通过传统的化疗有效控制但很少能达到完全缓解（CR），治愈几乎没有。大剂量化疗后予自体或异基因造血干细胞移植可提高MM缓解率及生存率。低危病人可行自体干细胞移植（ASCT），特别是序贯ASCT，高危病人应及时行异基因移植或应用新的治疗方法。异基因移植因移植物抗骨髓瘤作用（GVM）有可能治愈MM，但移植相关死亡率（TRM）较高制约了其广泛开展。为提高异基因移植成功率可使用低强度预处理方案。现将MM移植治疗的现状进行综述。     

自体造血干细胞移植的临床应用进展：急性白血病

自体造血干细胞移植（ASCT）是指采集患者骨髓或外周血干细胞低温保存,并于其接收大剂量化疗或放疗（预处理）后回输,以重建造血和免疫功能。ASCT包括自体外周血造血干细胞移植（APBSCT）及自体骨髓造血干细胞移植（ABMT）,以往多用于治疗血液系统恶性疾病（如白血病、淋巴瘤）,近年来逐渐用于实体瘤（如乳腺癌、卵巢癌）、自身免疫性疾病、缺血性疾病（如糖尿病足、心肌梗死）及中枢神经系统疾病等领域。现将其在临床的应用进展分述如下。     

实体瘤

化疗在延长生存期和提高实体瘤疗效方面均起重要作用,但药物毒性常使患者难以接受足量化疗。自20世纪80年代以来,在ASCT支持下恶性肿瘤的化疗剂量增加5～10倍,恶性肿瘤（尤其是转移性、全身性、难治性或进展期肿瘤）的治愈率和生存期进一步提高。近年来,ASCT广泛用于实体瘤如多发性骨髓瘤（MM）、乳腺癌、卵巢癌、神经母细胞瘤和小细胞肺癌等的治疗。     

淋巴瘤

恶性淋巴瘤（ML）是一组高度异质性的淋巴系统恶性增殖性疾病,分为霍奇金病（HD）和非霍奇金淋巴瘤（NHL）。放、化疗技术的进步使约60％的HD和近30％的NHL患者长期存活,但复发或持续未达缓解者（特别是中、高度恶性NHL）的长期生存改善不明显。大剂量放、化疗联合ASCT为ML提供了一种有效治疗手段。     

自身免疫性疾病

自身免疫性疾病（AID）是多种原因造成机体免疫功能紊乱,从而对自身抗原产生免疫应答,造成多系统损害的疾病。常规的糖皮质激素、免疫抑制剂及细胞毒性药物对危重或难治性AID疗效欠佳,近年来ASCT治疗危重或难治性自身免疫性疾病已在国内多中心进行。     

23例自体造血干细胞移植的临床护理

自体造血干细胞移(ASCT)是治疗白血病、恶性淋巴瘤等恶性疾病的重要手段，感染是其常见并发症和主要死亡原因。1993年11月～2002年11月，我院为23例(25例次)患者实施ASCT，取得满意疗效，现将护理体会报告如下。     

肠病相关T细胞淋巴瘤7例临床特征分析

目的探讨肠病相关T细胞淋巴瘤(EATL)的临床特点及其治疗策略。方法回顾性分析南京医科大学第一附属医院血液科7例初诊EATL患者的临床资料,探讨其治疗方案。结果 7例既往均无肠道疾病病史,均因消化道症状就诊。Ann Arbor及Lugano分期均以Ⅰ+Ⅱ期为主(6/7,85.7%)。6例完成6个疗程化疗,最大疗效均达完全缓解(CR),其中1例予自体造血干细胞移植(ASCT)巩固治疗。中位随访时间13个月(1~25个月),5例(包括ASCT)死亡。2年总生存率为25.7%。结论 EATL呈高度侵袭性,化疗可使患者短期获益,但容易复发。采用ASCT作为一线巩固治疗也难以获得长期疗效,异基因造血干细胞移植作为一线巩固治疗值得进一步探讨。     

多发性骨髓瘤患者自体造血干细胞移植后感染的临床特征

目的 了解多发性骨髓瘤(MM)自体造血干细胞移植(ASCT)后感染的临床特点.方法 回顾性分析在中山大学附属第一医院住院诊治并接受ASCT治疗的37例MM患者,记录移植后6个月内的感染类型、时间、病原体以及疗效和转归.结果 在ASCT后6个月内有33例(89.2%)患者在观察期间出现59例次感染,其中30例患者在观察期间出现34例次(57.6%)细菌感染,12例患者在观察期间出现15例次(25.4%)真菌感染.既往曾合并真菌感染患者在移植后发生真菌感染比例高于没有合并真菌感染的患者(P=0.040).观察期间分别出现4例(6.8%)巨细胞病毒(CMV)、3例(5.1%)带状疱疹病毒感染及3例(5.1%)HBV再激活.移植后早期感染中细菌感染占62.8%,真菌感染28.6%,病毒感染8.6%,其中病毒感染均为CMV感染,移植后早期未见水痘带状疱疹病毒和HBV感染.移植后中期感染中细菌感染占50.0%、真菌感染20.8%、病毒感染29.3%,移植后早期与中期感染比例差异无统计学意义(P=0.106).38例次(64.4%)感染在应用首选抗感染治疗即得到控制.3例(8.1%)由于感染相关死亡.结论 MM患者ASCT后感染发生率高,各种病原体均易感,需要尽早合理抗感染治疗,降低感染相关病死率.

Abstract：

Objective To explore the clinical features of infection in multiple myeloma (MM)undergoing autologous hematopoietic stem cell transplantation (ASCT). Methods Thirty-seven patients with MM undergoing ASCT were retrospectively analyzed for type and time of infection, pathogen, and outcome. Results Fifty-nine cases of infectious complications occurred in 33 patients (89. 2% ) after ASCT, with 34 cases (57.6%) of bacterial infections in 30 patients, 15 cases (25.4%) of fungal infections in 12 patients, 4 cases (6. 8% ) of cytomegalovirus (CMV) infection, 3 cases (5. 1% ) of herpes zoster virus infection and 3 cases (5. 1% ) of HBV reactivation. The proportion of bacterial infection, fungal infection and virus infection were 62. 8%, 28.6% and 8. 6% respectively in the early stage after ASCT, and 50. 0%, 20. 8% and 29. 3% respectively in the median stage. Response to first-line antibiotic therapy was seen in 38 cases (64. 4% ). Infection-related mortality was 8. 1% (3 cases). Conclusions The incidence of infection in MM patients undergoing ASCT is high and they are susceptible to all pathogens. It is important to choose the right antifungal agents as quickly as possible to reduce infection-related mortality.     

含硼替佐米方案的诱导治疗序贯自体造血干细胞移植治疗初诊时合并髓外病变的多发性骨髓瘤的疗效分析

目的:分析含硼替佐米诱导治疗序贯自体造血干细胞移植(ASCT)的治疗方案对初诊时合并髓外病变(EMD)的多发性骨髓瘤(MM)患者预后的影响。方法:回顾性分析244例初诊MM患者的临床资料,主要研究终点为总生存(OS)和无进展生存(PFS)。结果:入选的244例初诊患者中合并EMD者66例(27.0%)。244例患者按治疗方案分为3组:传统化疗组59例,持续新药治疗组87例,新药序贯ASCT组98例。传统化疗组中伴有EMD患者的中位PFS显著低于不伴EMD患者(7.433∶25.400个月,P=0.024),持续新药治疗组中伴有EMD患者的中位PFS与不伴EMD患者比较,差异无统计学意义(15.133∶27.100个月,P=0.269),硼替佐米序贯ASCT组中伴有EMD患者的中位PFS与不伴EMD患者比较,差异亦无统计学意义(46.667∶44.867个月,P=0.743)。在EMD患者中,硼替佐米序贯ASCT组与传统化疗组及持续新药治疗组相比,均可显著提高患者的中位PFS(P0.05)。传统化疗组中伴有EMD患者的中位OS显著低于不伴EMD患者(21.033∶34.667个月,P=0.043),持续新药治疗组中伴有EMD患者的中位OS显著低于不伴EMD患者(10.400∶44.300个月,P=0.004),而在硼替佐米序贯ASCT组中伴有EMD与不伴EMD患者间OS比较,差异无统计学意义(P=0.325)。在EMD患者中,硼替佐米序贯ASCT组与传统化疗组及持续新药治疗组相比,均可显著提高患者的中位OS(P0.005)。结论:含硼替佐米诱导治疗序贯ASCT的治疗方案可显著提高初诊伴EMD的MM患者的生存,克服EMD的不良预后影响。     

含苯达莫司汀预处理方案在淋巴瘤自体移植中疗效及安全性分析

目的:探讨含苯达莫司汀的移植预处理方案[BeEAM(苯达莫司汀+依托泊苷+阿糖胞苷+马法兰)和BeEAC(苯达莫司汀+依托泊苷+阿糖胞苷+环磷酰胺)]在淋巴瘤自体造血干细胞移植(ASCT)中的疗效及安全性。方法:回顾性分析2020年10月—2022年5月在潍坊市人民医院血液科接受ASCT的13例非霍奇金淋巴瘤患者,分析造血重建时间,并评估疗效及不良反应。结果:ASCT前完全缓解10例,部分缓解3例。13例患者移植后均造血重建,中性粒细胞中位植活时间10(9～16)d,血小板中位植活时间14(9～22)d。移植后中位随访11(3～19)个月,患者移植后3个月完全缓解率为84.6%(11/13),主要的2级以上不良反应为发热性中性粒细胞减少、恶心、呕吐、腹泻、口腔黏膜炎,无移植相关死亡。结论:BeEAM和BeEAC预处理后ASCT均是治疗恶性淋巴瘤安全、有效的方法,其远期疗效尚待长期随访观察。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.