造血干细胞移植进展

造血干细胞移植（ＳＣＴ）仍然在国内外蓬勃发展。四年前全国报告能进行异基因ＳＣＴ（ＡｌｌｏＳＣＴ）的为２２个单位，而至１９９９年，仅浙江省一个省份能进行ＡｌｌｏＳＣＴ的单位已超过１０个。全国除西藏外，各省自治区都有大小不同的ＳＣＴ单位。到１９９８年底的不完全统计，全国已作异基因ＳＣＴ７２０例。其中北京医科大学血液病研究所为３２６例。而ＩＢＭＴＲ（国际骨髓移植登记组）的报告，１９９７年ＡｌｌｏＢＭＴ的全球总数约１７０００例。ＡｌｌｏＳＣＴ的造血干细胞来源主要为骨髓。较少数为外周血，脐带血更…     

肝移植治疗原发性肝癌切除术后肝内复发七例

目的 探讨对原发性肝癌切除术后肝内复发患者进行肝移植手术的适应证和围手术期的治疗经验.方法 回顾性分析2000年9月至2005年9月间7例原发性肝癌切除术后肝内复发的患者接受原位肝移植治疗的临床资料,其中男性6例,女性1例,平均年龄43.7岁,肝移植术前均经病理学检查确诊为原发性肝癌,肿瘤组织学分级为高、中分化,肝癌切除术后无瘤期为6～31个月,均未发生肿瘤细胞侵犯大血管和肝外转移.所有患者均采用改良背驮式肝移植术.术后采用他克莫司(或西罗莫司)+霉酚酸酯+激素的三联免疫抑制方案.观察肝移植术后受者并发症及存活率情况.总结肝移植治疗原发性肝癌切除术后肝内复发的经验.结果 所有受者肝移植手术过程顺利,围手术期无死亡.1例术后22 h发生腹腔出血,1例术后13 d发生腹腔感染,1例术后4个月发生门静脉血栓,其余未发生严重并发症,7例受者均顺利出院.有3例受者分别于移植术后9、13及19个月时,因肿瘤复发而死亡,其余4例均长期无瘤存活,最长已达52个月.受者的1、2年存活率分别为85.7%和57.1%.结论 肝移植能有效治疗原发性肝癌切除术后肝内复发,受者适应证的选择和围手术期的辅助治疗非常关键.     

Liver transplantation for liver cancer

Results in the first 100 orthotopic liver allografts performed in the Cambridge-King's College Hospital series (1968–1980) are reported. Twenty-two patients survived beyond a year (age range, 16–59 years). Of these, 12 were cirrhotics and 10 were primary malignancies. Of the cirrhotics, 10 are alive, with the 2 deaths resulting from cholangitis. Two patients who had primary hepatic carcinoma are alive at 1 and 5 years following transplantation; the 8 deaths in this group were attributed to tumor recurrence (5 patients), sepsis (2 patients), and secondary cirrhosis possibly due to non-A non-B hepatitis (1 patient). Patients who survive for 6 months have a greatly increased chance of surviving the second 6 months and subsequently. Of the last 14 liver allografts (12 for cirrhosis and 2 for primary malignancy), there are 9 survivors. This mortality (36%) probably represents the results of better selection of the cirrhotics before they were too sick to withstand the operation; better control of rejection; and refinements in surgical procedure and anesthesia. For those patients surviving the first year, there is a 40% chance of the tumor's being eliminated. The late tumor recurrence rate is unacceptably high at 60%, however, and our criteria for patient selection have become increasingly selective.

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Résumé Cet article relate les 100 premiers cas de transplantation orthotopique du foie réalisée de 1968 à 1980 au Cambridge King's College Hospital. 22 opérés ont survécu plus de un an, leur âge allant de 16 à 59 ans; 12 étaient atteints de cirrhose et 10 de tumeurs primitives du foie. 10 des cirrhotiques transplantés sont vivants, 2 sont décédés d'angiocholite. Sur les 10 malades atteints de cancer primitif du foie 2 sont vivants la survie atteignant respectivement 1 an pour l'un, 5 ans pour l'autre mais 8 autres sont morts soit de récidive (5 cas), soit d'infection (2 cas) d'une cirrhose secondaire probablement post hépatitique.Les opérés qui survivent plus de 6 mois ont une grande chance de survivre un semestre de plus. Des 14 dernières transplantations: 12 pour cirrhose, 2 pour cancer primitif 9 ont survécu. Le taux de mortalité de 36 pour cent seulement correspond à une meilleure sélection des cirrhotiques à opérer, à un meilleur contrÔle des phénomènes de rejet et à une amé lioration de la technique chirurgicale et de l'anesthesie.Chez les opérés qui survécurent plus d'un an après transplantation pour cancer primitif le taux de récidive est de 60 pour cent. Il est inacceptable et doit inciter à une meilleure sélection des cas à opérer.

     

Allogeneic hemopoietic stem cell transplantation in solid tumors

The existence of a graft versus tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation is well established as a critical component for the success of the procedure in several hematologic malignancies. Although it has been suggested that a GVT effect might also be generated in patients affected by refractory solid tumors, the morbidity of conventional allogeneic hematopoietic stem cell transplantation has limited its investigation in these diseases. Recently introduced allogeneic nonmyeloablative regimens have greatly decreased morbidity and mortality related to transplants which retain a powerful GVT. On this basis, it has become possible to explore the existence of alloreactivity toward solid tumors. The present article reviews the early clinical results of this novel immunotherapeutic approach for solid tumors.     

Posttransplant lymphoproliferative disorder following nonmyeloablative allogeneic stem cell transplantation

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of conventional bone marrow/stem cell and solid organ transplantation. However, not much is known about PTLD following the more recently introduced nonmyeloablative allogeneic stem cell transplantation (NMST). This study reports the findings from two cases of PTLD following NMST and compares them to the one previously reported case. The donor origin of the PTLD was determined using short tandem repeat analysis, and B- and T-cell clonalities were evaluated by polymerase chain reaction. Two cases of PTLD evolved in a total of 70 patients who have undergone NMST at our institution from 1999 to 2003. Both patients received conditioning with Fludarabine/Cytoxan/Campath 1H (alemtuzumab, anti-CD52 antibody) and T-cell-depleted donor cells with Campath-1H. Both PTLDs were EBV positive (by immunohistochemistry and in situ hybridization) with diffuse large B-cell lymphoma morphology. Our findings indicate the incidence of PTLD following NMST is 3% (2 of 70 patients from our institution and 1 of 30 from the previously reported case). All three PTLDs arose 6 to 7 months after NMST and were rapidly fatal. The pathology of the PTLD in all cases was donor origin, EBV positive, diffuse large B-cell lymphoma.     

Bone marrow and hemopoietic stem cell transplantation

Background: Studies in the late 1940s and early 1950s showed that mice given marrow-ablative lethal doses of total body irradiation (TBI) survived if rescued by the infusion of hemopoietic stem cells or spleen shielding. Methods: Based on these observations, the first clinical studies were carried out in the mid-1950s. The modern era of bone marrow transplantation (BMT) began in the late 1960s, following the initial characterization of the major histocompatibility complex (MHC), termed HLA in man. Several preparative regimens are being used. Hemopoietic stem cells are obtained from the patient’s own (autologous) marrow or peripheral blood, from an identical (syngeneic) twin, or from another related or unrelated (allogeneic) donor. With allogeneic transplantation, T cells are depleted from donor marrow or immunosuppressive agents are given to prevent graft-versus-host disease (GVHD). Results: Many congenital or acquired malignant or nonmalignant diseases are being treated by BMT. Results vary dependent upon diagnosis, disease stage, type of transplant, and others. While survival may be 90% in patients with severe aplastic anemia and 80% in patients with chronic myeloid leukemia transplanted early in their course, survival may be only 10% with advanced leukemia. Outcome is less good with HLA-no-nidentical transplants GVHD and disease recurrence are the most frequent complications. Conclusions: Marrow or hemopoietic stem cell transplantation provides effective treatment (cure) for several diseases and is the treatment of choice for certain diagnoses. New modalities such as growth factors, cytokines or somatic gene transfer are currently being explored.     

High-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced extragonadal germ cell tumor--a case report]

We reported the experience of high-dose chemotherapy (HDC) combined with peripheral stem cell transplantation (PBSCT) in 29 years-old man with advanced retroperitoneal germ cell tumor accompanied with left supraclavicular lymph node metastases, who obtained complete remission after comprehensive treatment. The initial levels of serum AFP, hCG and beta-hCG were high at 30.2 ng/ml, 14,000 mIU/ml and 66 ng/ml, respectively. After 3 courses of chemotherapy (BEP regimen), while left supraclavicular lymph node swelling was disappeared, the retroperitoneal mass lesion persisted on CT scan. Not all of 3 markers fell to the normal range. After myelosuppressive chemotherapy (etoposide 500 mg/m2 Day 1-3), PBSCs were collected by two consecutive apheresises on Day 17 and 18. In total, 19.5 x 10(6)/kg CD 34 positive cells were obtained. The patient underwent PBSCT (all CD 34 positive cells were infused) on Day 0 following HDC (CBDCA 250 mg/m2/day, etoposide 300 mg/m2/day, IFM 1.5 g/m2/day, Day-7(-)-3, respectively). He became severely leukopenic and thrombopenic with nadir of 200/microliter on Day 6 and 2 x 10(4)/microliter on Day 2, respectively. By administration of platelet transfusion and G-CSF, the white blood cell counts and thrombocyte counts recovered to 6,400/microliter and 4.1 x 10(4)/microliter on Day 10, respectively. Microbiologically enterocolic and respiratory tract infections occurred with elevated body temperature (> 40 degrees C). Antibiotic and antimycotic treatments were continued until disappearance of all clinical and microbiological evidence. He was kept for 10 days in clean room. After HDC, all markers fell to the normal range, but the retroperitoneal residual mass still persisted. Resection of the residual mass and retroperitoneal lymph node dissection were performed with pathological examination revealing tissue necrosis without viable cell. The patient has survived with no sign of the disease for 9 months.     

肝移植治疗转移性肝癌临床价值及评价

肝移植是治疗部分不具备手术切除条件或者其他治疗方法无效的转移性肝癌病人的有效手段。由于不同来源的肝转移肿瘤行肝移植临床效果不同,临床上应严格把握手术适应证及治疗时机,以神经内分泌来源的肿瘤,尤其是类癌来源者肝移植效果最好,是目前转移性肝癌行肝移植手术的主要适应证,而结直肠癌肝转移行肝移植的价值还尚须进一步研究。目前,对于乳腺癌等其他肿瘤来源的转移性肝癌的报道较少。     

Role of adjuvant treatment in liver transplantation for advanced hepatocellular carcinoma

The results of liver transplantation for advanced hepatocellular carcinoma have been disappointing because of high recurrence rates, leading to low long-term survival; this indication remains controversial in an era of organ shortage. To continue to offer this treatment possibility, efforts were made to reduce recurrence and improve survival. The first approach is to maintain a strict selection policy excluding patients with extraheptic disease. The second approach is to test the efficacy of perioperative adjuvant therapies in patients selected for transplantation. The reasons for recurrence include: (1) undetected preoperative micrometastases, (2) intraoperative dissemination by surgical manipulation, and (3) acceleration of tumor growth by immunosuppression. Preoperative treatment, which may include systemic chemotherapy or arterial chemoembolization, seems necessary to limit tumor progression during the waiting period. Systemic chemotherapy has been tested pre-, intra-, and postoperatively. It is considered essential postoperatively and should be used as soon as possible after surgery (i.e., in the 1st postoperative week). Several teams have performed pilot studies that included rather limited numbers of patients, and the results were compared with those for historic controls. Published results show that chemoembolization creates tumor necrosis in most instances. This is efficient in limiting tumor progression but the effect on recurrence and survival is unknown. All authors who used postoperative chemotherapy reported improved survival over controls, with 50%–60% 3-year survival and up to 50% 5-year survival. However, recent results suggest that late recurrence may occur. Chemotherapy was usually well tolerated, although leukopenia, sometimes severe, was observed in most patients. The use of granulocyte colony-stimulating factor seems useful to overcome this problem. Perioperative adjuvant treatments seem to prolong survival in patients undergoing liver transplantation for advanced hepatocellular carcinoma, but delayed recurrence remains possible. Further studies are necessary; these should ideally be multicentric, prospective, and randomized. Received for publication on June 2, 1997; accepted on July 3, 1997     

Liver transplantation for primary and metastatic liver cancers

Liver transplantation for hepatic malignancies has emerged as a well‐documented and proven treatment modality. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, 15% of all liver transplants performed are for hepatocellular carcinoma (HCC). There is no controversy about the fact that liver transplantation for HCC in the adult population yields good results for patients whose tumour masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumours can be reliably selected to benefit from the procedure. In patients with small HCC at an early stage and preserved liver function, liver resection provides an alternative to transplant. Liver resection may offer similar survival results to orthotopic liver transplantation (OLT) in the short term, and does not carry the long‐term effects of immunosuppression; however, long‐term and disease‐free survival favours liver transplantation. Very promising results have been obtained for cholangiocarcinoma treated by aggressive combination therapies, including chemo‐ and radiotherapy followed by OLT. Survival rate in these selected patients can approach that of patients with cholestatic liver disease, and the role of transplantation now requires re‐evaluation. Similarly, hepatoblastoma is an excellent indication in paediatric patients with unresectable or recurrent tumours. Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation, even in the presence of extrahepatic metastases, unlike angiosarcoma which is associated with a very poor survival and considered as a contraindication. And finally for metastatic liver disease from neuroendocrine tumours, liver transplantation can result in long‐term survival and even cure in well selected patients. Conversely, the value of transplantation for colorectal liver metastases (currently a contraindication) requires further evaluation by well‐designed trials.     

Liver transplantation for primary hepatic cancer.

Although early survival following transplantation for primary hepatic cancer is excellent, previously reported high recurrence rates have generally discouraged liver replacement for this indication. Since the inception of the Boston Center for Liver Transplantation (BCLT) in 1983, 33 of 383 (8.6%) liver allograft recipients have undergone orthotopic transplantation as definitive treatment for otherwise unresectable cancer. Diagnoses included hepatocellular carcinoma (HCCA) in 24 patients (73%), and cholangiocarcinoma (CHCA) in 9 patients (27%). Actuarial survival rates for patients with hepatocellular carcinoma were 71%, 56%, and 42% at 1, 2, and 3 years, respectively. The actuarial survival rates for patients with cholangiocarcinoma were 89% at 6 months, and 56% at 1, 2, and 3 years. Of the nine patients with cholangiocarcinoma, 56% (5/9) developed recurrent disease. Although this recurrence rate is disheartening, because of the lack of other morbidity, long-term survival in these patients is comparable to patients with HCCA. In contrast, recurrent hepatocellular carcinoma developed in 25% of recipients (5/20) who survived longer than 3 months posttransplantation. Other causes of death in patients with hepatocellular carcinoma included perioperative complications, 16.6% (4/24); sepsis, 8.3% (2/24); coronary artery disease, 4.2% (1/24); and lymphoma, 4.2% (1/24). Favorable prognostic factors included: primary tumor less than 3 cm in size and absence of associated cirrhosis. These results emphasize that orthotopic liver transplantation can provide a long-term cure for approximately 50% of patients whose primary hepatic malignancy is unresectable by conventional procedures.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The present study was performed in order to investigate the efficacy and safety of high-dose chemotherapy for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem cell transplantation. Five patients received one cycle and two patients received two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one achieved a complete response and four achieved partial responses with markers negative. As a result of subsequent surgery for residual tumors, three of the four partial responders showed no residual cancer cells. One patient who did not undergo surgery received radiotherapy after the high-dose chemotherapy and the residual tumors disappeared. All five patients who had either a complete or partial response are still alive and without evidence of disease at 12, 27, 30, 37 and 40 months. One patient is alive with disease at 7 months and one died of progressive disease at 6 months. The hematologic recovery after high-dose chemotherapy was rapid and non-hematologic toxicities were usually mild and manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem cell transplantation is safe and effective for use in patients with far-advanced testicular cancer, particularly when the high-dose chemotherapy is conducted as the initial treatment. Further larger and long-term follow-up studies are needed to define the role of high-dose chemotherapy on testicular cancer.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

Between June 1998 and August 2000, five patients with germ cell tumor were treated with high-dose CEI: carboplatin (1,250 mg/m2), etoposide (1,500 mg/m2), and ifosfamide (7.5 g/m2), followed by peripheral blood stem cell transplantation (PBSCT) at Yokohama City University Hospital. All patients were classified into either poor risk group of International Germ Cell Consensus Classification or advanced extent of Indiana University stage, and received one cycle of high-dose CEI after 4-6 cycles of standard PEB (cisplatin, bleomycin, vinblastin) therapy. Three of the patients achieved complete response, one achieved partial response and one achieved no change after whole treatment. There were no fatal complications and no treatment-related deaths.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The aim of this study was to investigate the efficacy and safety of high-dose chemotherapy (HDCT) for the treatment of patients with advanced testicular cancer. METHODS: Fourteen patients were treated with high-dose carboplatin, etoposide and cyclophosphamide (with or without THP-adriamycin) followed by peripheral blood stem cell transplantation. The treatment was used for two refractory cases, a second relapse, and for consolidation after the first relapse in one case each. It was also used for nine cases as part of the first-line treatment following primary conventional-dose chemotherapy, and for one case as the first salvage for a late recurrent tumor of teratoma with malignant transformation. RESULTS: The first two patients who received intensive pretreatment with cisplatin-based chemotherapy did not respond to HDCT. The two patients who were treated with HDCT as the first or second salvage therapy achieved successful outcomes. The results for the subsequent nine patients (consisting of two with stage IIIC, five with IIIB2, one with IIB, and one extragonadal seminoma) were two progressive disease, three no change and four partial remission. Only three are alive with NED following salvage surgery. Finally, a case of teratoma with malignant transformation did not respond well to two cycles of HDCT. There were no marked adverse reactions except one episode of severe neutropenic colitis. CONCLUSIONS: The results demonstrated the limited efficacy of HDCT even in cases with a good to intermediate risk rating according to classification by the International Germ Cell Cancer Collaborative Group. Because treatment for relapse after HDCT is extremely difficult, new HDCT regimens consisting of drugs that are not used in induction chemotherapy need to be established.     

非清髓性造血干细胞移植后并发移植物抗宿主病的相关因素分析

目的 探讨和分析非清髓性造血干细胞移植(NST)后并发移植物抗宿主病(GVHD)的相关因素.方法 选择34例血液病患者,其中重型再生障碍性贫血(SAA)15例,重型β-地中海贫血(TM)1例,肿瘤性血液病18例;进行无关供者脐带血造血干细胞移植(UCBT)11例,同胞供者骨髓联合外周血干细胞移植7例,外周血造血干细胞移植(PBSCT)16例.移植前采用以抗胸腺细胞球蛋白(ATG)、抗淋巴细胞球蛋白(ALG)或者氟达拉滨强效免疫抑制为基础的非清髓性预处理方案.GVHD的预防采用短程的甲氨蝶呤(MTX)联合环孢素A(CsA).观察非清髓性造血干细胞移植后的临床特点以及急、慢性移植物抗宿主病的发生情况;分析发生慢性移植物抗宿主病(cGVHD)的相关因素.结果 NST的植入率为91.2%.移植后7例肿瘤性血液病患者形成了供、受者造血细胞混合嵌合体(MC),给予供者淋巴细胞输注(DLI)2～9次后,例由MC转变为供者造血细胞完全嵌合体(FDC).随访12(3～96)个月,共发生Ⅰ～Ⅱ度急性移植物抗宿主病(aGVHD)5例,GVHD 15例.经统计学分析,发现年龄大的肿瘤性血液病患者经以ATG为基础的NST后,再给予DLI,其cGVHD的发生率高,且合并感染,对治疗的反应差;而以氟达拉滨为基础的NST患者发生cGVHD后治疗反应较好.移植100 d前后患者分别死亡3例和5例,其中3例死于广泛性cGVHD.结论 患者的年龄大、有合并症、以ATG为基础的预处理方案、肿瘤性血液病是NST后患者并发cGVHD的危险因素.     

自体造血干细胞移植治疗周围动脉疾病的系统评价

目的评价自体造血干细胞移植治疗周围动脉疾病(peripheral arterial disease,PAD)的疗效和安全性。方法计算机检索中国生物医学文献数据库(CBM,1978年-2010年9月)、中国期刊全文数据库(CNKI,1979年-2010年9月)、MEDLINE(1950年-2010年9月)、Pubmed(1950年-2010年9月)、Embase(1970年-2010年9月)和Cochrane图书馆(2010年第4期),收集以自体造血干细胞移植为干预措施治疗PAD的随机对照试验(randomized controlled trials,RCTs),按照Cochrane系统评价方法,由2位研究者独立地对符合纳入标准的试验进行资料提取,并对纳入文献进行质量评估和对提取的有效数据进行Meta分析。结果有8个RCTs,共280例PAD患者322条肢体符合纳入标准,但大多数研究的方法学质量较差。Meta分析结果显示,自体造血干细胞移植治疗PAD较常规治疗能提高溃疡治愈率[RD=0.38,95%CI=(0.25,0.50)]、踝肱指数[MD=0.11,95%CI=(0.04,0.18)]、经皮氧分压[MD=7.33,95%CI=(3.14,11.51)]和无痛性行走距离[SMD=1.35,95%CI=(0.90,1.79)],可降低截肢率[RD=–0.19,95%CI=(—0.31,—0.07)]和静息痛评分[MD=—1.70,95%CI=(—2.15,—1.25)]。仅2个试验报道了自体造血干细胞移植治疗的不良反应,如肢体肿胀和血清磷酸激酶升高等。结论自体造血干细胞移植治疗PAD可能有一定疗效,但由于尚缺乏高质量的RCTs证据支持,其疗效尚不能作出最后结论,还需进行更多高质量RCTs才能得出肯定性结论。     

肝移植治疗原发性肝癌

目的探讨我国肝移植治疗原发性肝癌的手术适应证及效果。方法回顾性分析我院1999年2月至2004年连续施行的170例原位肝移植手术，对其中原发性肝癌62例的临床分期，手术方式及术后长期生存情况等进行分析，探讨手术指征及效果。结果62例肝癌肝移植病人，随访1～39个月，住院期间死亡4例（6．45％），存活病例1、2、3年肿瘤复发转移率分别为29．31％，41．38％，58．06％；1、2、3年生存率分别为87．45%，65．59％，42．06％，进一步分析发现肿瘤直径〈5cm者6例，全部无瘤生存；肿瘤伴门静脉主干癌栓者7例，除1例无瘤生存1年2个月外余均于1年内复发或死亡。结论晚期肝癌尚无门静脉主干癌栓者可作为我国肝移植指征，应进一步探索围手术期防治肝癌复发转移措施，进一步提高我国肝癌肝移植的疗效。     

供者淋巴细胞输注在恶性血液病非清髓性骨髓移植中的应用

目的探讨供者淋巴细胞输注(DLI)治疗非清髓性异基因造血干细胞移植后血液病复发的疗效。方法5例恶性血液病患者接受非清髓性造血干细胞移植,在形成混合性嵌合体和血液学部分缓解(例1～4)或进步(例5)后,进行DLI。移植后的4～5周进行第1次DLI,首次输注T淋巴细胞数量为(0.5～1.0)×105/kg,以后每隔3～4周逐渐增加输注的淋巴细胞数量,至(0.5～2.0)×108/kg,平均行DLI4.6次(3～8次)。结果例1～4分别经过7、3、2、3次DLI后,性染色体及DNA指纹图由混合性嵌合体转变为完全性嵌合体;例2、3经过DLI后消除了微小残留病,除例5仍然为混合性嵌合体和进步状态外,4例均达血液学完全缓解。例1、2和例3、4分别出现Ⅰ/Ⅱ度急性移植物抗宿主病和广泛/局限型慢性移植物抗宿主病,例2、4出现骨髓抑制。结论DLI可使异基因造血干细胞移植后短暂的混合性嵌合体向完全性嵌合体转变,并可清除微小残留病。     

转基因造血干细胞移植治疗小鼠甲状旁腺功能低下症的研究

目的　探讨输注整合有甲状旁腺素(PTH)基因的造血干细胞对甲状旁腺功能低下症的治疗效果。方法　将以pcDNA 3.1 PTH 为模板扩增出的PTH 基因插入到逆转录病毒载体MSCV中,得到含PTH基因的重组质粒,并转染PA317 包装细胞,以抗生素Geneticin筛选阳性克隆,获得重组有PTH基因的浓缩病毒悬液,以其感染人脐血造血干细胞,然后注入甲状旁腺功能低下症模型小鼠血中,术后观察小鼠症状的改善情况、血PTH及血钙浓度变化情况。结果　所获得的重组有PTH基因的浓缩病毒悬液,其病毒滴度为2×107 CFU/ml,PTH的分泌量为15 ng/48 h(106个细胞),未检测到有野生型病毒存在。实验组小鼠接受转染有PTH基因的血干细胞后,症状改善,血PTH及血钙浓度逐渐上升,并维持于接近正常水平;仅接受重组有PTH基因的浓缩病毒悬液的小鼠,短期内血PTH及血钙浓度明显升高,以后则呈缓慢下降趋势,并逐渐出现甲状旁腺功能低下症的表现;只接受造血干细胞移植的小鼠术后20 d左右全部死亡。结论　甲状旁腺功能低下症小鼠接受整合有PTH基因的造血干细胞静脉输注可获得较长期的治疗效果。     

Primary liver transplantation vs liver resection followed by transplantation for transplantable hepatocellular carcinoma:Liver functional quality and tumor characteristics matter

Liver resection(LR) and primary liver transplantation(LT) are two potentially curative treatment modalities for patients with hepatocellular carcinoma(HCC).If an underlying chronic liver disease exists,however,making a decision on which method should be selected is difficult.If a patient has no chronic liver disease,LR may be the preferable option with salvage transplantation(ST) in mind in case of recurrence.Presence of a moderate-to-severe liver failure accompanying HCC usually warrants primary LT.The treatment of patients with HCC and early-stage chronic liver disease remains controversial.The advantages of "LR-followed-by-STif-needed" strategy include less complicated index operation,no need for immunosuppression,use of donor livers for other patients in today’s organ shortage setting and comparable survival rates.However,primary LT has its own advantages as it also treats underlying chronic liver disease with carcinogenic potential,removes undetected tumor nodules and potentially eliminates need for a ST.An article recently published by Fuks et al in Hepatology offers an approach by which selecting between LR-followed-by-ST and immediate LT might be easier.Here we discuss the results of the aforementioned report in the light of currently available knowledge.