自体外周血造血干细胞移植治疗恶性淋巴瘤16例临床分析

目的：评价自体外周血造血干细胞移植（ＡＰＢＳＣＴ）治疗耐药,复发及晚期恶性淋巴瘤患者的疗效及影响因素,方法采用ＡＰＢＳＣＴ治疗恶性淋巴瘤患者１６例,其中霍奇金病患者２例,非霍奇金淋巴瘤患者１４例,移植时第１次完全缓解６例,第２次完全缓解２例,部分缓解８例;采集外周血造血干细胞均经动员剂动员,其中采用硫酸葡聚糖（ＤＳ）动员２例,惠尔血（Ｇ－ＣＳＦ）动员９例,惠尔血加生白能（Ｇ－ＣＳＦ加ＧＭ－ＣＳＦ）     

自体外周血造血干细胞移植治疗多发性骨髓瘤

目的:评价环磷酰胺(Cy)联合足叶乙苷(VP-16)和粒细胞集落刺激因子(G-CSF)方案干细胞动员效果及自体外周血造血干细胞移植(APBSCT)治疗多发性骨髓瘤(MM)的临床疗效。方法:8例MM患者给予Cy联合VP-16化疗加G-CSF动员造血干细胞,Cy 1 000-1 200 mg／(m2·d)×2 d,VP-16 500 mg／d×2 d,白细胞(WBC)<1．0×109／L后给G-CSF 300μg／d×6-9 d。当WBC>4．0×109／L,血小板>50×109／L后采集APBSC。采用2种预处理方案,马法兰200 mg／m2或140 mg／m2联合VP-16 1 000 mg及司莫司汀200 mg。结果:动员后采集的单个核细胞(MNC)为6．23(4．27-12．78)×108／kg;CD34 细胞为4．75(1．69-23．15)×106／kg;粒细胞-巨噬细胞集落形成单位(CFU-GM)集落为84．5(5．4-300．4)个／104细胞。APBSCT后中性粒细胞恢复至>0．5×109／L的中位时间 9．5 d。在8例患者中,6例获得完全缓解,1例部分缓解,1例未缓解。中位生存期46(23-54)个月,中位无病生存期12(0-39)个月。结论:Cy联合VP-16加G-CSF作为动员方案,能够采集足够量的APBSC;APBCST治疗MM安全有效。     

自体外周血造血干细胞移植治疗系统性红斑狼疮的初步观察

目的探讨自体外周血造血干细胞移植(APBSCT)治疗系统性红斑狼疮(SLE)的可行性及临床效果。方法对8例女性难治性SLE病人进行APBSCT。采集的干细胞的单个核细胞计数平均为1.6×108/kg[(0.07～2.6)×108/kg]。预处理方案为环磷酰胺(50mg·kg-1·d-1,-5～-2d)静脉滴注及兔抗人淋巴细胞免疫球蛋白(10mg·kg-1·d-1,-3～-1d)静脉滴注。从移植前后皮肤红斑的变化,尿的改变,SLE相关的免疫指标的变化,移植后造血重建情况,移植的并发症等方面进行评价。结果8例病人均获得成功植入,外周血白细胞总数>1.0×109/L的平均时间为9.5d,中性粒细胞计数>0.5×109/L的平均时间为10d,白细胞总数恢复正常的平均时间为14d,血小板计数>50×109/L的平均时间为30d,血红蛋白含量平均在移植后第28天升至100g/L。移植后SLE临床症状均消失,尿蛋白转阴,自身抗体大部分转阴。移植相关并发症中,均出现血清病样预处理反应,2例出现严重的低血压;4例有出血性膀胱炎;2例出现败血症;4例发生霉菌感染;2例发生间质性肺炎。随访时间2个月～2.5年。结论APBSCT治疗SLE有较好的近期疗效,但观察病例及时间有限,远期疗效还需更长时间的观察。对药物治疗难以奏效的SLE病例,该法不失为一种更佳的选择。     

自体外周血造血干细胞移植治疗系统性红斑狼疮的临床观察

目的 探讨自体外周血造血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效和安全性.方法 10例难治性SLE患者接受APBSCT治疗,应用环磷酰胺(CTX)2～4 g/m2和粒细胞集落刺激因子5～10 μg·kg-1·d-1行外周血造血干细胞动员;预处理包括CTX(50 mg·kg-1·-1,-6～-3 d)和抗胸腺细胞球蛋白(ATG,15～20 mg·kg-1·d-1,-2 d、-1 d、1 d、2 d).患者输注的CD34+细胞＞2×106/kg.评估治疗前后临床表现、SLE疾病活动指数(SLEDAI)和免疫指标的变化.结果 APBSCT后10例SLE患者的临床症状缓解,SLEDAI评分降低,均获得造血重建,中性粒细胞＞0.5×109/L的中位数时间为9.5 d,血小板＞20×109/L中位数时间是11 d;尿蛋白减少或消失,抗核抗体滴度减低或转阴,补体水平升高;移植相关的并发症有:2例败血症,2例巨细胞病毒感染,1例出现肾毒性,3例急性左心衰竭,3例心律失常,无移植相关死亡.结论 APBSCT能够改善SLE患者的疾病活动和免疫学指标,是一种有效的治疗难治性SLE的方法,但远期疗效需进一步观察.     

自体外周血干细胞移植治疗小儿恶性淋巴瘤相关因素分析

随着小儿恶性淋巴瘤诊治研究的不断深入，自体外周血干细胞移植(APBSC)以其能加速重建造血功能，延长患儿无病生存乃至根治疾病，愈来愈受到临床重视。2001～2003年，我们应用APBSC治疗5例恶性淋巴瘤患儿，疗效较满意。本文就干细胞采集、分离保存、回输等相关因素分析报告如下。     

非清髓性自体外周血造血干细胞移植治疗系统性红斑狼疮远期疗效分析

目的探讨非清髓性自体外周血造血干细胞移植(NAST)治疗系统性红斑狼疮(SLE)的远期疗效。方法总结中山大学附属第五医院2002年11月至2005年10月4例成功接受NAST的SLE患者移植后的随访情况。非清髓性预处理移植前1～2 d静脉滴注阿糖胞苷200 mg/(kg.d)及环磷酰胺40 mg/(kg.d)。评价患者移植前后的相关症状体征、远期并发症及免疫功能的变化。结果白细胞总数恢复正常的中位时间12 d,血小板>100×109/L的中位时间为10 d,血红蛋白>120 g/L的中位时间为22 d。随访中,NAST后4例患者临床症状和体症均消失,淋巴细胞亚群检测显示:CD4+及CD4+/CD8+均恢复正常。1例男性患者移植4年后妻子正常受孕并产下一健康女婴。3例女性均恢复正常工作与生活。结论 NAST造血重建快,远期疗效确切。SLE患者NAST治疗后生活质量较好。     

自体外周血造血干细胞移植治疗恶性淋巴瘤

恶性淋巴瘤（ＭＬ）包括霍奇金氏淋巴瘤（ＨＬ）和非霍奇金氏淋巴瘤（ＮＨＬ）,是一组起源于淋巴组织的高度异质性的恶性克隆性疾病。近年来,尽管化、放疗技术已有了较大的进展,但对中度或高度恶性的ＭＬ,特别是临床中、晚期和有Ｂ组症状的患者,即使能够完全缓解（ＣＲ）,多数最终复发或产生耐药而不治。因而,越来越多的ＭＬ患者,选择了造血干细胞移植治疗,尤其是复发和难治耐药的病例。异基因移植无肿瘤细胞的污染并具移植物抗肿瘤（ＧＶＴ）作用,有移植后复发率低的优点,但ＨＬＡ相合供者的缺乏和较高的移植相关死亡率,使得它…     

老年恶性血液病患者自体外周血造血干细胞动员的临床研究

自体造血干细胞移植是多种血液系统恶性肿瘤及自身免疫性疾病的主要治疗手段之一.外周血干细胞（PBSC）动员和采集,因其对供体伤害小、费用少及移植后造血功能重建早,在自体移植中已逐步替代骨髓造血干细胞[1].老年患者是否可行自体移植,取决于是否可采集到足够数量的自体PBSC.为此,我们对老年患者自体PBSC动员进行了临床观察,以探讨老年患者自体PBSC动员效果及影响因素。     

自体外周血造血干细胞采集的护理

自体外周血造血干细胞移植（autologous peripheral blood stem cell transplantation，APBSCT）因采集简便，对造血、免疫功能恢复快，又不受供者的影响，现已经成为恶性血液病、实体瘤，某些自身免疫性疾病等的根治性治疗方法之一。APBSCT成功的基础是获得足够数量的APBSC，而保证造血干细胞采集过程顺利进行是确保造血干细胞产量及质量的关键。本文总结了7例19例次APBSC采集术的护理，现报告如下。     

自体外周血干细胞移植治疗失代偿期肝硬化

目的评价自体外周血干细胞移植治疗失代偿期肝硬化的效果。方法选择42例住院治疗的失代偿期肝硬化患者,分为干细胞移植组20例和对照组22例,两组均予以相同的内科综合治疗,干细胞移植组加行经肝动脉自体外周血干细胞移植术,观察患者术后乏力、纳差、腹胀等主要症状的变化,检测移植术后4、8、12、24周肝功能、凝血功能等指标的变化,同期检测对照组的变化。结果两组患者在治疗后观察期间的主要症状乏力、纳差、腹胀均有改善。20例干细胞移植组患者手术均成功,无特殊不良反应及并发症。术后8、12、24周干细胞移植组患者肝功白蛋白均较术前明显回升(P0.05),与对照组比较差异有统计学意义(P0.05)。术后12周、24周细胞移植组凝血酶原活动度以及术后24周细胞移植组凝血酶原时间较术前明显改善(P0.05),但组间比较无统计学差异。术后12周、24周Child评分较术前及对照组明显改善,差异有统计学意义(P0.01)。结论经肝动脉自体外周血干细胞移植治疗失代偿期肝硬化是一种安全、有效的微创治疗方法,可在一定程度上改善患者的低蛋白血症及凝血功能。     

异基因外周血造血干细胞移植治疗难治性白血病(附1例报告)

对 1例难治性急性粒 -单细胞白血病 (AML - M4 b)患者施行异基因外周血造血干细胞移植 (allo-PBSCT ) ,以 Cy/ TBI方案预处理后 ,输注 HL A完全相合的同胞供者经 G- CSF动员的外周血单个核细胞(PBMNCs) 9.0× 10 8/ kg,其中 CD34 细胞 6 .2 5× 10 6 / kg;移植物抗宿主病 (GVHD)的预防用 Cs A MTX方案。结果 : 15天时 ,外周血中性粒细胞 >0 .5× 10 9/ L,血小板 >5 0× 10 9/ L; 30天时 ,外周血三系均完全恢复正常。仅有 度皮肤 GVHD发生。认为对于难治性白血病 ,如有 HL A相合供者 ,应及早行异基因造血干细胞移植 (allo-HSCT)特别是 allo- PBSCT,具有受者造血与免疫功能重建快等优点     

Detecting of the minimal residual disease contaminated in peripheral blood stem cell transplantation in the B-cell malignant lymphoma patients.

For sufficient collection of hemopoietic stem cells from peripheral blood for autologous peripheral blood stem cell transplantation (PBSCT), four patients with B-cell-type non-Hodgkin lymphoma (B-NHL) were examined for the appearance of circulating hemopoietic progenitors in blood (PSC) during the hemopoietic recovery phase following marrow ablative therapy in combination with or without administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Each patient received only chemotherapy in the first course, and rhG-CSF (1 microgram/kg/day) was administered for 14 consecutive days from the last day of the second chemotherapy. In the second chemotherapy course with rhG-CSF administration, white blood cell (WBC) counts demonstrated two peaks, and the appearance of granulocyte-macrophage precursor cells (CFU-GM) in blood at the maximum level was coincident with the second peak of WBC elevation. Erythroid precursor cells (BFU-E) were also detectable in blood after chemotherapy but the peak level was not enhanced by the use of rhG-CSF. To determine whether the minimal residual disease (MRD) cells were contaminated in PSC corrected from blood, kappa-lambda imaging (KLI) analysis was performed to detect the malignant B-cell population (mBp) before and after chemotherapy. No mBp was found in two of four patients in blood, although three of them were involved with mBp in bone marrow. The presence of mBp was detected in two patients both before and after chemotherapy, even though these cells were hardly detected morphologically, suggesting the necessity of judging for the incidence of contamination of MRD cells when collecting PSCs.     

CD34+-selected autologous peripheral blood stem cell transplantation conditioned with total body irradiation for malignant lymphoma: increased risk of infectious complications

Although high-dose chemotherapy with autologous peripheral blood stem cell transplantation (autoPBSCT) has been shown or confirmed to be an effective treatment for high-risk and relapsed non-Hodgkin's lymphoma (NHL), relapse after autoPBSCT remains a serious problem. In a clinical trial to overcome relapse, we adopted a treatment plan in which PBSCs purified in vitro to CD34+ cells to deplete tumor cells (CD34+ autoPBSCT), total body irradiation (TBI) of 1200 cGy, and melphalan, 180 mg/m2, were used as a preconditioning regimen. Eighteen patients with relapsed or high-risk NHL participated in the study. This study compared the incidence of complications following CD34+ autoPBSCT preconditioned with the TBI regimen (n = 10): the TBI group; CD34+ autoPBSCT with the non-TBI regimen (n = 8): the non-TBI group; and unselected autoPBSCT with the non-TBI regimen (n = 19): the unselected autoPBSCT control group. After day 30 posttransplantation, 6 of 10 patients treated with the TBI regimen developed 11 infectious complications in total, compared with only 1 of 8 patients treated with the non-TBI regimen and 4 of 19 patients given unselected autoPBSCT. Two fatal complications occurred in the TBI group, but none occurred in the other 2 groups. The CD4+ lymphocyte count at 1 month posttransplantation was significantly lower in the TBI group than in the unselected autoPBSCT group. These findings suggest that the addition of TBI to the preconditioning regimen for CD34+ autoPBSCT is associated with an increased incidence of severe infectious complications after transplantation.     

自体外周血干细胞移植治疗血液恶性肿瘤231例临床观察

目的观察自体外周血干细胞移植(APBSCT)治疗血液恶性肿瘤的疗效。方法2001年3月至2007年2月对第三军医大学新桥医院231例血液恶性肿瘤患者施行APBSCT,其中急性淋巴细胞白血病(ALL)45例,急性髓性白血病(AML)34例,非霍奇金淋巴瘤(NHL)100例,霍奇金淋巴瘤(HD)31例,多发性骨髓瘤(MM)21例,观察临床疗效和并发症。结果除1例ALL外,230例患者移植后造血功能均快速重建。ALL首次完全缓解(CR1)28例患者中无病存活(DFS)13例,带病存活4例,死亡11例;ALL二次缓解(CR2)17例患者中DFS3例,带病存活4例,死亡10例。AMLCR120例患者中DFS11例,带病存活3例,死亡6例;AMLCR214例患者中DFS6例,带病存活2例,死亡6例。NHLCR159例患者中DFS43例,带病存活7例,死亡9例;NHLCR230例患者中DFS18例,带病存活5例,死亡7例;NHL未缓解(NR)11例患者中DFS2例,带病存活4例,死亡5例。HDCR110例患者中DFS10例;HD部分缓解(PR)15例患者中DFS12例,带病存活3例;HD疾病复发(RE)6例患者中DFS3例,带病存活2例,死亡1例。MM21例患者中DFS7例,带病存活6例,死亡8例。结论APBSCT是一种安全有效的血液肿瘤治疗方法。     

Risk of neutropenic fever and early infectious complications after autologous peripheral blood stem cell transplantation for malignant diseases

Autologous peripheral blood stem cell transplantation (auto-PBSCT) has facilitated high-dose chemotherapy for the treatment of various types of malignancy, but the factors affecting the treatment outcome have not been well defined. We evaluated patients who underwent auto-PBSCT (46 patients with hematological malignancies and 39 with solid tumors) to elucidate the risks of background factors, including age, in association with infectious complications. In contrast to former reports, faster engraftment did not influence the incidence of documented infection or neutropenic fever, whereas high age (age > or = 50 years old) and delayed platelet recovery (> or = 18 days) were demonstrated to be positively involved. The odds ratio (OR) for documented infection in elderly patients was 4.94 (95% confidence interval, 1.22-15.8). Another risk factor of infection was the HD-ICE regimen (ifosfamide, carboplatin, etoposide) given to patients with solid tumors (OR, 8.00; 95% confidence interval, 1.61-39.7). In conclusion, we found that elderly patients and patients on the HD-ICE regimen have a higher risk of infectious complications even after auto-PBSCT. Although the clinical indications for auto-PBSCT can be extended to elderly patients, thorough precautions should be taken against infectious complications during the pre-engraftment phase.     

Progress in haematopoietic stem cell transplantation for multiple myeloma

High-dose myeloablative treatment followed by autologous haematopoietic stem cell transplantation has significantly improved survival of patients younger than 65 years of age with multiple myeloma as compared with conventional chemotherapy. However, all patients seem to relapse and molecular remissions are rare. Results of allogeneic transplantation, still hampered by high transplant-related mortality, have improved dramatically over the last 5-6 years and this is an option for patients younger than 50-55 years old. The relapse rate is lower than with autologous transplantation and molecular remissions are frequent. Some patients are still in complete haematological remission more the 10 years following transplantation. Autologous transplantation followed by nonmyeloablative allogeneic transplantation is on trial and may be a way to eventually cure a fraction of younger patients with multiple myeloma.     

Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients

We have analysed the incidence and risk factors for the occurrence of invasive fungal infections (IFI) among 395 recipients of an allogeneic peripheral blood stem cell transplantation (PBSCT) from a human leucocyte antigen (HLA)-identical sibling. IFI (n = 50) occurred in 46 patients, giving an overall probability of 14%. There were 12 cases of invasive candidiasis (3%), with only one death. Non-Candida IFI occurred in 37 patients (12% probability), mostly invasive aspergillosis (n = 32). In multivariate analysis the only two significant variables associated with a higher risk of developing a non-Candida IFI were the development of moderate-to-severe graft-versus-host disease (GvHD, P < 0.0001; OR 4.6) and having received steroid prophylaxis for GvHD (P = 0.04; OR 2.1). In multivariate analysis the variables associated with a lower overall survival after PBSCT were development of a non-Candida IFI (P < 0.0001; OR 5.6), non-early disease phase (P = 0.0001; OR 1.9), steroid prophylaxis (P = 0.02; OR 1.4), moderate-to-severe GvHD (P = 0.01; OR 1.6) and cytomegalovirus infection post transplant (P = 0.001; OR 1.8). Our results show that non-Candida IFI (in particular aspergillosis) was an important cause of infectious morbidity and mortality after an HLA-identical sibling PBSCT, while invasive candidiasis was rare. Use of steroid prophylaxis and, in particular, the development of moderate-to-severe GvHD post transplant were risk factors for non-Candida IFI. Prophylactic strategies for these infections should thus take into account these risk factors.