自体造血干细胞移植治疗急性白血病患者143例疗效分析

目的:评价自体造血干细胞移植(AHSCT)治疗急性白血病的疗效。方法:自1986年10月～2005年3月,采用AHSCT治疗急性白血病患者143例(男83,女60),中位年龄26(9～52)岁。其中急性非淋巴细胞白血病(ANLL)76例(CR167例,CR2,CR3及复发者9例),急性淋巴细胞白血病(ALL)64例(CR154例,CR2及复发者10例),急性杂合性白血病CR13例。预处理方案主要包括环磷酰胺(Cy)120mg/kg+单次全身放疗(TBI)9～10Gy或马利兰(Bu)16mg/kg或马法兰(Mel)160～180mg/m2+AraC4g/m2。结果:除5例患者因移植早期发生移植相关死亡而未重建造血外,其余138例患者均重建造血。移植相关死亡22例(15.4%),AHSCT后73例生存者已中位随访93(1～203)月。急性白血病患者CR1期与≥CR2期ABMT者5年无病生存率(DFS)分别为51.8%±4.6%与26.3%±10.1%(P=0.024),累积复发率分别为38%±4.8%与49.2%±12.4%(P=0.397)。结论:为降低急性白血病复发率和提高患者无病生存率,无HLA匹配同胞供者的CR1期急性白血病患者适合进行AHSCT治疗。     

自体造血干细胞移植治疗恶性血液病的临床研究

应用自体造血干细胞移植(ASCT)治疗恶性血液病11例,并随机选择病种、年龄及性别相似的13例应用常规化疗的恶性血液病作为对照.结果显示所有患者均造血重建,白细胞降至0的中位时间为6(3～10)天,持续5(1～14)天,中性粒细胞恢复至＞0.5×109/L的时间为18(13～24)天.在不输血小板情况下,维持血小板计数＞20×109/L中位时间为23(17～42)天.中位持续完全缓解时间(CCR)667.7(83～1885)天.3年无病生存率46%,而对照组3年无病生存率仅为18%,P＝0.035.提示自体造血干细胞移植可提高生存质量,明显提高无病生存率.     

自体造血干细胞移植治疗恶性淋巴瘤18例临床分析

目的探讨自体造血干细胞移植治疗恶性淋巴瘤的临床效果。方法选取恶性淋巴瘤患者18例为研究对象,其中非霍奇金淋巴瘤患者13例,霍奇金淋巴瘤患者5例;移植前状态CR18例,CR26例,PR4例。外周血造血干细胞动员采用大剂量环磷酰胺联合粒细胞集落刺激因子进行治疗,预处理采用司莫司汀、阿糖胞苷、依托泊苷以及马法兰联合治疗方式。结果患者进行外周血干细胞采集均采集到足够的干细胞。平均MNC为(5.97±1.24)×108/kg,平均CD34+为(4.46±1.03)×106/kg。治疗18例患者,无移植相关死亡病例;移植治疗后随访6~66个月,患者3年无病生存率为66.7%。结论采用自体造血干细胞移植为中心的序贯疗法治疗恶性淋巴瘤患者较为安全有效,无明显不良反应,值得临床推广应用。     

自体造血干细胞移植在临床中的应用

1 概述 自体造血干细胞移植(AHSCT)是指在特定时期采集患者自身的造血干细胞,在体外保存或经特殊处理(如净化、转基因等),并于患者接受高剂量化疗或放疗后回输,以促进其造血恢复或造血重建.目前,AHSCT已广泛用于治疗造血系统恶性肿瘤和实体瘤超大剂量放疗后的骨髓移植,也用于某些恶性疾病的治疗.     

硼替佐米联合地塞米松方案诱导后续不同方法巩固治疗多发性骨髓瘤长期疗效观察

目的比较以硼替佐米联合地塞米松(VD)方案诱导治疗达到完全缓解/接近完全缓解(CR/nCR)疗效的多发性骨髓瘤(MM)患者接受自体造血干细胞移植和VD方案作为不同巩固治疗的疗效和预后。方法回顾性分析2006年7月至2009年2月中山大学附属第一医院血液科23例经VD方案诱导达到CR/nCR疗效的MM患者的临床资料。16例(移植组)接受自体造血干细胞移植作为巩固,7例(非移植组)继续应用VD方案巩固2～4个疗程。两组患者巩固治疗后均接受50～200mg反应停维持治疗直至复发。结果移植组患者在巩固治疗后有7例患者(7/16,43.8%)疗效进一步增加,中位随访15个月时所有患者均存活,处于无疾病进展状态;非移植组在中位随访13个月时,2例患者疾病进展,再次诱导治疗无效死亡。VD方案不影响干细胞采集,所有患者的干细胞植入顺利,中位中性粒细胞恢复时间16d(10～30d),中位血小板恢复时间20d(9～100d)。VD方案的常见不良反应包括胃肠道(47.8%)、疲乏(26.1%)、血小板减少(26.1%)、周围神经炎(52.2%)和感染(26.1%),3～4级毒副反应发生率低。结论自体造血干细胞移植的地位仍不可替代,VD方案诱导化疗后以自体移植作为巩固,是治疗年轻MM患者的最佳选择。     

时辰高剂量化疗联合自体骨髓移植治疗非霍奇金淋巴瘤的长期随访

目的　探讨在自体骨髓 (造血干细胞 )移植技术支持下应用时辰高剂量的环磷酰胺、足叶乙甙、阿糖胞苷和表阿霉素等组成 COAE预处理化疗方案治疗预后差的中高度恶性非霍奇金淋巴瘤 (NHL )的疗效。方法　观察 11例 NHL患者应用该项治疗后造血与免疫功能重建、长期无病生存率、毒副作用及移植相关死亡等 ,选用COX回归模型分析性别、年龄、预处理方案、分期、移植时状态等对无病生存时间的影响。结果　所有患者均获得造血与免疫功能重建。随访 1、3、5年 ,无病生存率分别为 81.8%、6 3.6 %、5 4 .5 % ,最长存活 9年。 5例复发(4 5 .4 % )。无移植相关死亡。结论　该法在给药时间上进行了创新 ,提高了疗效 ,减低了高剂量化疗的毒副作用。该法作为有不良预后因素的中高度恶性 NHL患者诱导化疗达完全缓解后强化治疗手段的远期疗效显著 ,优于常规化疗 ,能够改善生存率     

自体外周血干细胞移植、生物治疗、长间歇维持化疗序贯治疗恶性血液病的临床研究

目的评价自体外周血干细胞移植治疗高龄恶性血液病的疗效。方法将60例老年患者分为移植组与非移植组,其中移植组的34例高龄恶性血液病患者首次缓解并经3~4个周期强化治疗后,行自体外周血干细胞移植,预处理方案采用MAC、M及CY TBI,造血重建后予以大剂量IL-2行生物治疗4个疗程,之后每3~4个月予以长间歇维持化疗1次,常用方案包括TA、MA、MP、CTOD等;非移植组的26例患者采用常规的化疗治疗。结果34例患者移植后均成功重建造血,无一例移植相关死亡。移植后维持化疗满2年的患者有20例,有10例复发(50%),其中6例死亡。34例患者中16例复发(47.1%),其中死亡8例。3年无病生存率为(43.0±7.1)%。26例常规化疗的患者中20例复发(76.9%),其中有12例死亡,3年无病生存率为(19.2±6.2)%。结论自体外周血干细胞移植、生物治疗、长间歇维持化疗序贯治疗高龄恶性血液病,治疗相关死亡率低,无病生存率较高,可作为改善高龄恶性血液病治疗效果的重要措施。     

造血干细胞移植治疗嗜酸性粒细胞增多综合征1例并文献复习

目的:探讨自体造血干细胞移植对嗜酸性粒细胞增多综合征(HES)的疗效.方法:选取采用羟基脲、泼尼松等治疗后病情反复的嗜酸性粒细胞增多综合征(HES)患者1例,采集自体外周血造血干细胞,预处理用Ara-c1.5 g/m2、VP16 0.4 g/m2静脉滴注连用2 d,预处理后回输自体造血干细胞悬液.观察自体造血干细胞移植前、后临床表现和血象指标的变化并复习相关文献.结果:自体造血干细胞移植后患者的临床症状明显缓解,血象各指标恢复正常.结论:自体造血干细胞移植对HES有较好的疗效,远期疗效还需长期随访.     

自体外周血干细胞移植和自体骨髓移植的临床疗效比较

目的 :比较自体外周血干细胞移植 (APBSCT)与自体骨髓移植 (ABMT)的临床疗效。方法 :用ABMT治疗 2 1例 ,用 APBSc T治疗 2 0例。预处理方案包括全身照射 (TBI) 6 .6～ 8.8Gy加环磷酰胺 (CTX) 10 0～ 12 0 m g/ kg或 TBI 2 .0 Gy加全淋巴照射 (TL I) 4 .0 Gy加 CTX 10 0～ 12 0 m g/ kg加 Vp- 16 6 0 0～ 10 0 0 m g/ m2加环己亚硝脲 (CCNU ) 2 0 0 m g方案或卡氮芥 (BCNU ) 2 0 0 mg/ m2 加 CTX 12 0 mg/ kg加 VP- 16 80 0 m g/ m2 方案或 MAC方案 (马法兰 140 m g/ m2 加 Ara- C 2～ 4g/ m2 加 CTX 12 0 m g/ kg)。结果 :ABMT组造血重建 2 0例 ,移植相关死亡 2例 (9.5 % ) ,复发 4例 (2 0 % ) ,2年无病生存率 (DFS) 6 8.5 0 %± 10 .87% ;而 APBSCT组均获造血重建 ,无移植相关死亡 ,复发 5例 (2 5 % ) ,2年 DFS为 6 2 .34 %± 14.2 6 %。两组差异无显著性意义。结论 :APBSCT与ABMT的疗效相当。     

自体造血干细胞移植联合CIK细胞免疫疗法治疗难治性淋巴瘤的临床研究

目的:探讨自体造血干细胞移植联合细胞因子诱导的杀伤细胞(CIK细胞)免疫疗法治疗难治性淋巴瘤的安全性及有效性。方法:48例难治性淋巴瘤患者分为2组,其中23例进行自体造血干细胞移植联合自体外周血来源的CIK细胞治疗,25例仅采用自体造血干细胞移植治疗。治疗后观察移植疗效,CIK细胞治疗相关不良反应,比较2组3年随访下的无病生存及总生存情况。结果:48例难治性淋巴瘤患者均顺利完成自体造血干细胞移植,无移植相关死亡,自体移植治疗后2组患者的完全缓解率分别为34.8%和44%(P=0.514);部分缓解率47.8%和32%(P=0.263);CIK治疗组11/23例患者(47.8%)出现1~2级的自限性畏寒、发热等输注反应。CIK细胞治疗组与移植组的患者1年,2年,3年的总生存率(OS)分别为(95.7%±4.3%)∶(79.8%±8.1%);(90.3%±6.5%)∶(70.9%±9.3%);(69.7%±1.4%)∶(49.8%±11.1%);无疾病进展生存(PFS)分别为:(82.6%±7.9%)∶(68.0%±9.3%);(59.7%±11.4%)∶(36.0%±9.6%);(44.8%±11.5%)∶(18.0%±8.0%)。2组OS比较差异无统计学意义(P=0.197);PFS比较CIK组较好(P=0.024)。结论:在自体造血干细胞移植基础上联合CIK细胞治疗可以进一步提高难治性淋巴瘤的疗效。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

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.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

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.     

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.     

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.