用BU3-CY预处理方案进行减量的异基因骨髓移植

目的 :探索 BU3- CY预处理方案在减低预处理剂量骨髓移植 (RI- BMT)中的作用。方法 :以 BU3- CY减低预处理剂量的方法对 7例白血病患者作 RI- HSCT,供者均为亲兄弟姐妹 (rela-tive sibling donor,RSD) ,其中有 3例为 HL A5 / 6位点相合者 ,输入 G- CSF动员的供者单个核细胞(MNC) 4× 10 8/ kg～ 8× 10 8/ kg,以 MTX,Cs A,MMF预防 GVHD。结果 :7例患者均成功植入 ,WBC上升到 1× 10 9/ L 为 +11天 (10天～ 15天 ) ,Plt上升到 2 0× 10 9/ L 为 +12天 (9天～ 17天 ) ,除口腔炎外 ,无明显的毒副作用。移植后 (11天～ 4 5天 )均有经 DNA检测证实的完全供者嵌合 (FDC) ,例 1于+2 0天时为混合嵌合 ,+45天时为完全嵌合。急性 GVHD3例 ,1例为 度 GVHD,+6 2天时死亡 ,2例为 度 GVHD治愈 ,3例有慢性 GVHD,2例为广泛性 ,1例为局限性。 6 / 7例无病存活 6个月 (2个月～ 12个月 )。结论 :BU3- CY的预处理方案可作为减低预处理剂量骨髓移植 (RI- BMT或 RI- HSCT)的预处理方法     

非血缘及HLA配型不合造血干细胞移植的临床研究

 目的 探讨非血缘及HLA配型不全相合造血干细胞移植在白血病治疗中的应用。方法非血缘脐血移植治疗儿童白血病3例,非血缘异基因外周血造血干细胞移植治疗白血病1例,HLA配型不全相合外周血造血干细胞移植治疗白血病1例。结果 5例患者完全植入,+15～+25天白细胞（WBC）＞1.0×109／L-1,＋35～＋51天血小板（Plt）＞20×109／L-1。例1出现急性移植物抗宿主病（aGVHD）Ⅰ度;例4 aGVHD Ⅳ度;例5出现肝静脉闭塞综合征（VOD）、aGVHDⅠ度、出血性膀胱炎（HC）;例2移植后6个月复发,放弃治疗死亡;余4例正常生活或工作。结论　非血缘及HLA配型不全相合造血干细胞移植治疗白血病是安全有效的。     

异基因造血干细胞移植治疗白血病的临床研究

目的探讨异基因造血干细胞移植治疗白血病。方法脐血移植治疗儿童白血病3例,异基因外周血造血干细胞移植治疗白血病3例。结果6例患者完全植入,+15～+25天白细胞(WBC)>1.0×109/L,+35天～+51天血小板(Plt)>20×109/L。例1出现急性GVHDⅠ度,例5出现急性GVHDⅣ度,例6出现肝静脉闭塞综合征(VOD)、急性GVHDⅠ度、出血性膀胱炎(HC),例2移植后6个月复发,放弃治疗死亡。余5例正常生活或工作。结论异基因造血干细胞移植治疗白血病是安全有效的方法。     

同胞间脐血移植治疗小儿急性淋巴细胞性白血病的时机选择与随访(附3例分析)

目的:同胞脐血具有组织相容性高,易获得HLA配型一致而不易被排斥的特点,本文报道同胞间脐血移植治疗3例小儿急性淋巴细胞性白血病的疗效并进行随访。方法:对3例急性淋巴细胞性白血病(2例高白细胞性高危CR1,1例标危并发中枢神经系统白血病CR2),进行了同胞间脐血移植,HLA高分辨2例全相合,1例5个位点相合。预处理选用白消安/环磷酰胺为主方案。于0d回输脐血,MNC数量为2.65×107/kg,2.23×107/kg,2.18×107/kg;CD34+细胞数量为1.92×107/kg,1.39×105/kg。预防移植物抗宿主病采用环孢霉素A、甲基泼尼松龙和甲氨蝶呤的方案。结果:中性粒细胞绝对值(ANC)≥0.5×109/L的天数分别是+13d、+24d、+20d,PLT≥20×109/L的时间为+19d、+46d、+21d,移植证据均为供者型。3例出现Ⅰ-Ⅱ度GVHD,均控制。随访中发生Ⅱ度慢性GVHD 1例,现长期存活2例,生活良好。结论:同胞间脐血移植是儿童高危白血病有效的治疗手段,急、慢性GVHD发生率较低,存在移植物抗白血病作用,更为安全可靠。     

非清髓异基因外周造血干细胞移植治疗老年重型再障报告

目的 :探讨非清髓异基因外周造血干细胞移植 (NAST)治疗老年重型再生障碍性贫血 (SAA)的方法及疗效。方法 :采用非清髓预处理的异基因外周造血干细胞移植治疗老年 SAA患者1例。供受者 HL A配型及红细胞 ABO血型完全相合。预处理方案主要由环胞霉素 A(Cs A)、抗淋巴细胞球蛋白 (ATG)和环磷酰胺组成。用环胞霉素 A和霉酚双酯 (MMF)预防移植物抗宿主病(GVHD)。采用 STR- PCR定量方法检测供者细胞植入情况。结果 :该例老年 SAA患者顺利度过移植后造血抑制期 ,于移植后第 8天外周血 WBC升至 0 .8× 10 9/ L,第 14天血象三系恢复 ,于移植后第 14天、30天、90天及 180天时检测供者细胞植入率均为完全植入。患者未出现移植物抗宿主病 ,现己无病存活 31个月。结论 :非清髓异基因外周造血干细胞移植简便安全 ,并发症少 ,疗效好 ,为老年 SAA的治疗提供了新手段     

同胞间脐血移植治疗小儿急性淋巴细胞性白血病的时机选择与随访（附3例分析）

目的：同胞脐血具有组织相容性高,易获得HLA配型一致而不易被排斥的特点,本文报道同胞间脐血移植治疗3例小儿急性淋巴细胞性白血病的疗效并进行随访。方法：对3例急性淋巴细胞性白血病（2例高白细胞性高危CR1,1例标危并发中枢神经系统白血病CR2）,进行了同胞间脐血移植,HLA高分辨2例全相合,1例5个位点相合。预处理选用白消安/环磷酰胺为主方案。于0d回输脐血,MNC数量为2.65×107/kg,2.23×107/kg,2.18×107/kg;CD34＋细胞数量为1.92×107/kg,1.39×105/kg。预防移植物抗宿主病采用环孢霉素A、甲基泼尼松龙和甲氨蝶呤的方案。结果：中性粒细胞绝对值（ANC）≥0.5×109/L的天数分别是＋13d、＋24d、＋20d,PLT≥20×109/L的时间为＋19d、＋46d、＋21d,移植证据均为供者型。3例出现Ⅰ-Ⅱ度GVHD,均控制。随访中发生Ⅱ度慢性GVHD 1例,现长期存活2例,生活良好。结论：同胞间脐血移植是儿童高危白血病有效的治疗手段,急、慢性GVHD发生率较低,存在移植物抗白血病作用,更为安全可靠。     

异基因外周血干细胞移植后GVHD的防治

目的　研究 Allo- PBSCT治疗白血病时 GVHD发生状况 ,探讨其有效防治方法。方法　成年人白血病 13例 ,经预处理 (CTX12 m g/ kg- 1· d- 1 ,TBI9Gy～ 10 Gy)后移植 HL A相合的经 G- CSF3 0 0 μg/ d动员的外周血单个核细胞 10× 10 9/ kg;应用小剂量环孢菌素 A联合短程 MTX预防 GVHD。结果　 GVHD发生率 5 3 .4 % ,其中 度以上 GVHD占 4 3 % (3 / 7) ,无直接死于 GVHD者。结论　 PBSCT患者 GVHD发生率和严重程度没有明显增高 ,CSA血药浓度与 GVHD发生密切相关 ,NK细胞比例可能协助诊断 GVHD。     

干细胞移植治疗骨髓增生异常综合征13例

 目的　探讨干细胞移植（HSCT）在骨髓增生异常综合征（MDS）治疗中的疗效以及预处理方式的选择。方法　对13例MDS患者行异基因造血干细胞移植 （allo-HSCT）（包括HLA配型全相合10例、半相合2例、脐血移植1例）。输注单个核细胞（MNC） 6.92（2.65～21.33）×108／kg,CD34细胞4.47（1.49～10.22）×106／kg。其中,5例选择全身照射+氟达拉滨+环磷酰胺（TBI+Flud+Cy）方案预处理,3例白消安（BU）／Cy预处理,3例TBI+CY,2例采用阿糖胞苷（Ara-C）+BU+Cy+替尼泊苷（VM26）预处理。移植物抗宿主病（GVHD）的预防：2例HLA配型半相合者给予抗胸腺细胞球蛋白（ATG）联合环孢素A（CsA）加短程甲氨蝶呤（MTX）治疗,并于移植后1～28 d持续给予霉酚酸酯（MMF）,其他病例仅给予CsA加短程MTX。结果　13例患者中9例造血完全重建,移植相关死亡4例。结论　HSCT是可以治愈MDS的有效方法。预处理选择应采取个体化。     

异基因造血干细胞移植治疗复发性急性白血病

目的　探索异基因造血干细胞移植 (Allo HSCT)治疗复发性急性白血病的可行性。方法　 2例患者均为早期复发的急性白血病患者 ,1例由台湾慈济会骨髓捐赠中心提供HLA配型完全相同的非亲缘性骨髓血。另 1例则由其胞弟提供外周血干细胞。两者均予改良的马利兰 ,环磷酰胺 (BU/CY)方案进行预处理。移植物抗宿主病 (GVHD)的预防两者均用环胞菌素A (CSA)、甲氨蝶呤(MTX) ,例 1还加用霉酚酸酯 (MMF)。例 2采用供者淋巴细胞输注 (DLI)预防白血病复发。结果　移植后两者均获造血重建 ,中性粒细胞 (ANC) >0 5× 10 9/L ,血小板 (BPC) >2 0× 10 9/L的时间例 1为移植后第 2 1天及 72天 ;例 2为第 10天及 15天 ,前者第 43天骨髓染色体检查由 46 ,XY转为 46 ,XX ,第 113天血型由B转为供者型O ;后者第 14天骨髓染色体检查由移植前的 46 ,XX转为移植后的 46 ,XY。移植过程例 1发生严重的急性移植物抗宿主病 (aGVHD) ,6个月后死于间质性肺炎 (IP)。 2例患者在 3～ 6个月的随访中均无复发。结论　通过GVHD及DLI所介导的移植物抗白血病效应 (GVL) ,可以使复发性急性白血病患者获得移植后长期造血重建。     

实时定量聚合酶链反应在异基因造血干细胞移植后巨细胞病毒感染的诊断和治疗中的应用

 【摘要】　目的　探讨异基因造血干细胞移植（allo-HSCT）后应用实时定量聚合酶链反应（RQ-PCR）技术检测巨细胞病毒（CMV）DNA拷贝数,以指导对CMV感染的临床诊断及治疗。方法　回顾分析接受allo-HSCT的23例患者,按移植方式分为同胞全相合HSCT 11例,亲缘间单倍体HSCT 12例。移植后均采用RQ-PCR技术检测CMV-DNA,＞1000拷贝数／ml为CMV阳性。全部患者在预处理阶段-9天至-2天应用更昔洛韦预防CMV感染。抢先治疗首选更昔洛韦,血常规低于正常者选用缬更昔洛韦或膦甲酸钠。结果　23例allo-HSCT患者中共13例发生14例次（56.5 %）CMV感染,2例发生CMV病（8.7 %）。同胞全相合的11例患者发生CMV感染2例（18.2 %）,亲缘间单倍体的12例患者发生CMV感染11例12例次（91.7 %）。发病中位时间为+41天（+30～+62天）。经治疗12例患者13例次CMV-DNA转阴（92.3 %）,1例死亡（7.7 %）。结论　RQ-PCR技术检测血浆CMV-DNA是监测CMV感染的可靠手段,有利于指导临床抗CMV治疗,减少CMV病的发生。     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 or elmex gelee. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In nonirradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 or elmex gelee led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected by remineralization than the dentine.     

Consultation multidisciplinaire pour les patients atteints d’une pathologie tumorale (carcinome infiltrant ou lésion précancéreuse) liée à HPV : la consultation multidisciplinaire papillomavirus

Given the recent increase in the number of human papillomavirus (HPV)-induced cancers in other locations than gynaecological, the number of patients with two cancers at distinct sites, and because of the lack of exhaustive data, we decided to create a multidisciplinary network around an HPV consultation at the Georges-Pompidou European Hospital (HEGP). This network aims to set up the best tools for detecting HPV-associated “multisite” precancerous lesions in order to determine the possible impact of dedicated care for this at-risk population. This monthly consultation was created at the HEGP in June 2014. It is currently organized around five consultations: gynaecological, ENT, urological, digestive and immunological. Every patient who has been diagnosed with HPV-related cancer and whose care is provided at the HEGP is offered this particular follow-up: systematically, once the initial lesion has been treated, the patient is convened annually for a day during which it benefits from the consultations mentioned above. A consultation with a psychologist is systematically proposed. Local samples are taken at each site: a cytological examination, the analysis of known predictive and prognostic virological markers are carried out. This study fits more broadly in a theme of clinical and fundamental research around cancers related to HPV.     

Differentiation state and invasiveness of human breast cancer cell lines

Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and ₁ and ₄ integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47D_CO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.