异基因造血干细胞移植治疗白血病76例临床观察

目的观察不同来源的异基因造血干细胞移植治疗白血病的疗效并探讨主要并发症的处理方案。方法对2001年9月至2007年3月第四军医大学西京医院血液科76例白血病患者行异基因造血干细胞移植治疗,其中慢性粒细胞白血病34例,急性髓性白血病24例,急性淋巴细胞白血病15例,T细胞淋巴瘤/白血病3例。人类白细胞抗原(HLA)全相合的同胞供者57例,1个HLA位点不合同胞供者3例,HLA单倍型半相合同胞供者7例,非血缘供者9例。预处理方案采用改良的马利兰联合环磷酰胺(BUCY)或改良的环磷酰胺联合全身放疗及阿糖胞苷或鬼臼乙叉甙(CyTBI Ara-c/VP-16)方案。采用标准的环孢素A(CsA)联合短期甲氨蝶呤(MTX)方案预防移植物抗宿主病(GVHD);无关供者移植加用抗人胸腺细胞球蛋白,单倍型半相合移植同时加用CD25单克隆抗体。结果96.1%(73/76)获得植入。24.7%(18/73)出现急性GVHD,32.9%(24/73)出现慢性GVHD;合并重症肝静脉闭塞病2例;并发纯红细胞性再生障碍性贫血5例。随访3~72个月,现存活56.6%(43/76),43.4%(33/76)在移植后1~36个月时死亡,19例死于白血病复发,14例死于移植相关并发症。结论多种来源的异基因造血干细胞移植是治疗白血病的有效方法,于慢性粒细胞白血病慢性期、急性白血病缓解期移植效果较好,移植前处于高危难治状态的病例复发率仍较高。     

异基因造血干细胞移植治疗白血病20例临床观察

目的探讨不同类型异基因造血干细胞移植(allo-HSCT)治疗白血病的疗效、造血重建及存活情况。方法哈尔滨血液病肿瘤研究所2003年3月至2006年7月进行异基因造血干细胞移植的白血病患者20例,其中同胞间人类白细胞抗原(HLA)相合的异基因外周血造血干细胞移植(allo-PBSCT)12例,无亲缘关系HLA不全相合脐血移植(UCBT)4例,无关供者的异基因外周血干细胞移植(其中1例HLA-CW位点亚型不合)3例,无关供者骨髓移植1例(经过去除红细胞处理)。结果19/20受者获造血重建,UCBT患者造血重建速度较HLA相合的同胞allo-PBSCT慢,异基因造血干细胞移植后20例患者中发生急性移植物抗宿主病(aGVHD)7例,其中4例Ⅰ~Ⅱ度,3例Ⅲ~Ⅳ度。3例患者死于复发,3例死于移植物抗宿主病(GVHD),另15例至今仍无病存活,中位存活时间30(1~41)个月。结论allo-HSCT是目前治愈白血病的有效方法,对于无同胞HLA相合的供者,选择较高细胞数量,HLA1~2个位点不合的UCBT仍然有效、可行。     

双份HLA不全相合非血缘脐血移植成功治疗成人急性髓细胞白血病1例报告并文献复习

目的：探讨双份HLA不全相合非血缘脐血移植(UCBT)治疗成人急性髓细胞白血病的造血、免疫重建及植人状态。方法：l例急性单核细胞白血病，43岁，体重75kg，采用双份HLA不全相合非血缘脐血移植治疗急性髓细胞白血病患者1例。预处理方案由白消胺(BU)、环磷酰胺(CY)和抗胸腺细胞球蛋白(ATG)组成。应用环孢素A(CsA)和骁悉(MMF)预防移植物抗宿主病(GVHD)。结果：移植后19天造血重建，NK细胞和B细胞分别于术后30天和120天恢复正常，DNA短串联重复序列多态型(STR)和HLA差异分析显示移植后17天、30天、150天基因型表现为完全性双份供者的嵌合型，未发生GVHD。随访150天，血常规、骨髓象检查正常。结论：双份HLA配型不合的脐血用于成人脐血移植是可行的。     

HLA不全相合外周血造血干细胞移植治疗急性白血病的临床观察

目的：探讨HLA不全相合外周血造血干细胞移植(PBSCT)治疗急性白血病(AL)的可行性。方法：应用HLA1个位点不合亲缘供体PBSCT治疗急性白血病2例，采用BUCY加ALG进行预处理，采用环孢素A、甲氨喋呤、霉酚酸酯和抗CD25单抗等联合预防移植物抗宿主病(GVHD)。结果：2例患者均获造血重建，并发Ⅱ度急性GVHD及局限性慢性GVHD。随访19个月均无病生存，恢复正常生活。结论：对缺乏HLA完全相合同胞供体的白血病患者，应用HLA不全相合的亲缘供体PBSCT治疗急性白血病具有一定的应用前景。     

含全身照射预处理方案行HLA不相合非去T造血干细胞移植治疗白血病8例临床分析

目的探讨采用全身照射(TBI)预处理方案行人类白细胞抗原(HLA)配型不相合亲缘供者非去T异基因造血干细胞移植(allo-HSCT)治疗白血病的疗效。方法2002年4月至2007年1月北京大学血液病研究所8例采用TBI预处理方案行HLA不合非去T亲缘供者allo-HSCT的白血病患者,其中急性髓性白血病(AML)3例,急性淋巴细胞性白血病(ALL)4例,慢性粒细胞白血病1例;预处理方案采用TBI加环磷酰胺(CY)方案4例,TBI加氟达拉滨(FLU)方案4例;干细胞来源包括骨髓和外周血造血干细胞移植6例,外周血造血干细胞移植(PBSCT)2例;移植物抗宿主病(GVHD)预防采用经典的环孢素A(CsA) 霉酚酸酯(MMF) 短程甲氨蝶呤(MTX)方案。结果8例供者采集单个核细胞(MNC)中位数为7.39(6.27~12.46)×108/kg,粒细胞植入中位时间11(11~13)d,血小板植入中位时间13(11~21)d。5例发生Ⅰ~Ⅱ度急性GVHD,2例出现慢性广泛性GVHD,无严重急性GVHD或因GVHD死亡病例。中位随访时间9(3~53)个月,除1例复发存活外,其余病例无病存活。结论对于HLA不相合异基因造血干细胞移植,TBI方案是一种比较安全、有效的非去T预处理方案,对于高危和二次移植患者同样有效。     

HLA半相合非清髓异基因造血干细胞移植治疗难治性急性白血病1例

目的探讨HLA半相合非清髓异基因造血干细胞移植(NAST)在治疗难治性急性白血病中的作用。方法2002-06采用非清髓预处理的NAST治疗军事医学科学院附属307医院难治性急性髓性白血病患者1例。预处理方案主要由抗淋巴细胞球蛋白(ATG)、阿糖胞苷(Ara-C)、氟达拉滨(Flu)和环磷酰胺(CTX)等组成。移植物抗宿主病(GVHD)的预防采用环孢素A(CSA)、霉酚双酯(MMF)、甲氨蝶呤(MTX)和CD25单抗。结果患者移植过程顺利,于移植后第100d转为完全供者型植入。患者于移植后出现皮肤Ⅰ度GVHD,经治疗后好转。结论应用HLA半相合NAST治疗难治性急性白血病患者,简便安全,疗效好,为无HLA相合供者的白血病患者治疗开辟了新的治疗手段。     

人类白细胞抗原不合或单倍体亲属供者造血干细胞移植

异基因造血干细胞移植(allo-HSCT)是重症血液病的主要根治性治疗方法。除人类白细胞抗原(HLA)相合的健康同胞为首选供者外,非血缘、脐带血和亲属HLA不合或单倍体造血干细胞都作为重要的干细胞来源进入了临床。美国的统计资料显示只有不超过40%的患者可以找到HLA相合的同胞供者。白人中找到非血缘HLA相合供者的机会约为75%,但在少数人种中这一几率低于50%。尽管如此,非血缘供者的查询过程耗时长,使得许多急性患者无法在最适宜的时机接受移植。脐带血来源的造血干细胞虽然可以立即得到,对供者不构成任何负担而且运输过程污染机会小,但…     

亲属间HLA半相合干细胞移植治疗难治复发性白血病患者30例疗效分析

目的观察亲属间HLA半相合干细胞移植(SCT)治疗难治复发性白血病(RL)的疗效。方法对自1998年8月至2004年8月期间进行HLA半相合SCT治疗30例RL的治疗结果进行分析。结果30例患者均为RL,其中急性非淋巴细胞白血病13例,急性淋巴细胞白血病10例,慢性粒细胞白血病6例,Ⅳ期淋巴瘤1例。男18例,女12例,中位年龄25(3~52)岁。30例患者均接受HLA半相合SCT。12例为父母给子女,4例为子女给父母,其余为同胞。HLA3个位点不合12例,HLA2个位点不合13例,5例HLA1个位点不合。预处理方案为氟达拉宾、马利兰、环磷酰胺方案,部分患者在此方案基础上加用抗人胸腺细胞球蛋白。平均移植单个核细胞数5·0(2·9~8·0)×108/kg,CD3+4细胞数为5·5(3·0~6·5)×106/kg。30例中24例完全供者植入,3例供、受者部分嵌合,经供者淋巴细胞输注转为完全供者型;1例移植失败,1例移植后2d死于重症霉菌感染,1例移植后28d死于重症肝静脉阻塞病;移植后WBC>1·0×109/L平均时间14(11~18)d,血小板>20×109/L时间15(11~18)d。6例发生Ⅲ~Ⅳ度重症移植物抗宿主病(GVHD),7例发生慢性GVHD,白血病缓解率90%,随访3~60个月,平均生存时间为16·9个月。7例复发,其中2例脑膜白血病复发,复发中位时间为10(3~24)个月,14例生存,10例仍无病生存。结论HLA半相合SCT能使大部分RL患者缓解,也能使部分RL患者获长期生存;HLA半相合SCT具有较强的移植物抗白血病效应,但在疾病状态下进行HLA半相合SCT,白血病仍会复发。     

HLA位点不全相合的异基因干细胞移植治疗白血病的临床分析

目的：探讨HLA不完全相合的造血干细胞移植治疗白血病的新方法.方法：将8例白血病患者接受FBC预处理方案后行异基因粒细胞集落刺激因子（G-CSF）动员的骨髓和外周血干细胞联合移植，观察造血重建和移植相关的并发症情况.结果：1例2位点不合患者植入失败，其余7例完全植入，白细胞恢复时间13.5 d，血小板恢复15.1 d，7例患者Ⅰ～Ⅱ度急性移植物抗宿主病（GVHD）发生率57.1%（4/7），局限性慢性GVHD发生率83.3%，未出现严重的心、肝和肺脏并发症.移植后6个月生存率62.5%.结论：用FBC预处理方案和GCSF动员后的骨髓和外周血干细胞联合移植的方法对于HLA不相合的移植安全有效。     

配型不合造血干细胞移植治疗重型再生障碍性贫血的疗效及安全性

目的 研究人类白细胞抗原(HLA)配型不合造血干细胞移植治疗重型再生障碍性贫血(SAA)的疗效和安全性.方法 从2006年1月至2010年5月共入选17例SAA患者接受配型不合造血干细胞移植治疗,供受者间HLA 2个位点不合8例,3个位点不合9例,以改良马利兰/环磷酰胺+抗人胸腺细胞免疫球蛋白(BU/CY+ATG)为预处理方案,进行骨髓加外周血干细胞移植.结果 所有病例均达到完全供者植入.发生Ⅲ～Ⅳ度急性移植物抗宿主病(GVHD)3例,14例可评估病例中,广泛型慢性GVHD 1例;中位随访285(60～1670)d,11例患者生存,9例血象恢复正常,另2例脱离输血.6例患者死于移植相关合并症.结论 当无HLA配型相合同胞供者时,SAA患者采用HLA配型不合移植是可行的治疗选择.

Abstract：

Objective To study the efficacy and safety of human leukocyte antigen (HLA)mismatched hematopoietic stem cell transplantation (HSCT) on severe aplastic anemia(SAA). Methods From January 2006 to May 2010, 17 patients received mismatched HSCT. HLA antigens were 3-locimismatched in 9 patients, 2-loci-mismatched in 8. All patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) primed bone marrow cells plus peripheral blood stem cells after modified busulfan/cyclophosphamide + antithymocyte immunoglobulin (BU/CY + ATG ) conditioning regimen. Results All patients achieved full donor type engraftment. Grade Ⅲ-Ⅳ graft versus host disease (GVHD) occurred in 3 patients and extensive chronic GVHD in 1. With a median following-up time of 285(60-1670) d, 11 patients were alive, 9 of them had normal blood counts and the other 2 were blood transfusion independent. Six patients died of transplant-related complications. Conclusion Mismatched HSCT is a feasible and safe option for SAA patients without sibling identical donors.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.