Autologous bone marrow transplantation in paediatric solid tumours

Massive therapy with ABMT is now an established treatment modality in paediatric oncology. The technical aspects and most treatment-related complications have been clarified and many phase II studies have shown encouraging results. In advanced neuroblastoma the poor outlook with conventional chemotherapy has stimulated extensive investigation of forms of massive therapy. Current results from several centres indicate that although the median survival is increased, long-term survival in an unselected group of stage IV patients is unlikely to exceed 30% with current regimens. In the future, management of this disease may involve the use of more intensive induction regimens to improve the quality of remission at the time of ABMT, which remains the single most important prognostic factor. Improved purging procedures involve the possible use of double massive therapy regimens and a combination of immunological and chemical treatments. In other paediatric tumours, the relative rarity and limited indications for ABMT make the evaluation of its role more difficult. Preliminary results in advanced rhabdomyosarcoma and Ewing's sarcoma are none the less encouraging and justify further investigation. The value of purging procedures remains controversial and their assessment has been hampered by the lack of sensitive clonogenic assays to detect residual tumour cells. However, neuroblastoma has provided a useful model for the investigation of physical, immunological and chemical procedures. Massive therapy is expensive, time consuming, and carries a high cost in patient morbidity and stress to the families involved. As with any new treatment, it must be adequately assessed in phase III, randomized studies. The ENSG and SIOP trials are a beginning and the future of massive therapy in the paediatric patient will, we hope, be based on a rigorous and scientific comparison with other treatment modalities.     

Autologous bone marrow transplantation after histologic transformation of indolent B cell malignancies.

The role of high-dose therapy and autologous stem cell transplantation in diffuse large B cell lymphoma (DLBCL) after transformation is controversial. We have retrospectively analyzed patients with chemosensitive disease and a history of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma who underwent high-dose chemoradiotherapy and bone marrow transplantation (BMT) with anti-B cell monoclonal antibody-purged autologous marrow for DLBCL. Between December 1982 and August 1997, 27 patients underwent autologous BMT using a uniform ablative regimen with cyclophosphamide, total-body irradiation, and bone marrow purging. All patients received multiple chemotherapy regimens before autologous BMT. At bone marrow (BM) harvest, only 44% of patients were in complete remission, and overt BM infiltration was present in 37%. After cyclophosphamide and total-body irradiation, no treatment-related deaths were seen. Eleven of the 27 patients relapsed, and four patients developed myelodysplasia/acute myelogenous leukemia. In seven patients in whom pathologic studies were available after relapse, the histology remained DLBCL. Twelve patients remained alive and in complete remission with a median follow-up of 36 months (range 10-132). The disease-free survival and overall survival are estimated to be 46% (90% confidence interval 28-64) and 58% (40-76) at 5 years, respectively. Patients whose disease underwent histologic transformation within 18 months of their initial diagnosis of indolent lymphoma had significantly better overall survival. Selected patients with histologic transformation, particularly those whose transformation occurs early in the course of their disease and who remain chemosensitive, may experience prolonged survival after autoBMT.     

自体骨髓单个核细胞移植治疗下肢动脉闭塞症

背景：下肢缺血性疾病治疗中血管再生技术已成为研究的热点。 目的：观察自体骨髓单个核细胞移植后下肢缺血性疾病患者肢体缺血症状的改善情况。 方法：东南大学医学院附属江阴医院胸心血管外科及南京大学医学院附属南京市鼓楼医院血管外科于2007年10月至2011年10月采用自体骨髓单个核细胞治疗35例下肢缺血性疾病患者,抽取自体骨髓单个核细胞,沿下肢动脉走行路径进行多点注射,测定患肢疼痛程度、冷感缓解程度、踝肱指数、经皮氧分压及皮肤溃疡或坏疽面积的改变,动脉造影观察血管新生情况。 结果与结论：①疼痛评分：骨髓单个核细胞移植后2个月和1年的疼痛评分均较移植前有下降趋势,差异有显著性意义(P < 0.05)。移植后2个月与移植后1年评分比较,差异无显著性意义(P > 0.05)。②冷感缓解程度：移植后2个月缓解率为51%,移植后1年缓解率为60%,与移植前比较差异有显著性意义(P < 0.05)。③踝肱指数的变化：移植2个月踝肱指数均较移植前有升高趋势,但差异无显著性意义 (P > 0.05),移植后1年踝肱指数较移植前有明显增高,差异有显著性意义(P < 0.05)。④经皮氧分压的变化：对经皮氧分压增加值进行比较,移植后2个月及移植后1年均较移植前明显增加,差异有显著性意义(P < 0.05),移植后1年与移植后2个月比较差异无显著性意义(P > 0.05)。⑤行走距离：移植后2个月和移植后1年的行走距离明显增加,与移植前比较差异有显著性意义(P < 0.05),移植后1年与移植后2个月比较差异无显著性意义(P > 0.05)。⑥溃疡创面的变化：移植后2个月和1年的溃疡面积均较移植前有缩小趋势,差异有显著性意义(P < 0.05)。⑦新生血管评价：移植后股动脉造影显示缺血下肢注射骨髓单个核细胞的部位毛细血管增生明显,且与已有的毛细血管相互连接形成侧支循环,促进了缺血下肢的血液供应。     

自体骨髓干细胞移植治疗下肢缺血性疾病☆

背景：骨髓干细胞可通过多种机制促进缺血下肢新生血管生成,形成新的侧支,改善局部血供。 目的：总结骨髓干细胞在下肢缺血性疾病中的研究进展。 方法：应用计算机检索PubMed及CNKI数据库2001-12/2011-12与骨髓干细胞移植治疗下肢缺血性疾病相关的文献,检索词“bone marrow stem cells,lower extremists ischemia”。 结果与结论：骨髓干细胞可定向到达坏死组织参与组织再生,形成和分泌许多血管活性生长因子促进血管新生,促进细胞增殖和分化,利于组织细胞再生。关于骨髓干细胞移植治疗下肢缺血性疾病方面的研究虽已取得较大进展,但仍存在许多问题,如种子细胞的保存,细胞体外培养中分化增殖的调控机制不十分清楚,产生骨骼肌细胞的生物力学性能不太满意,修复组织内细胞分子生物学特性不明确等。     

自体骨髓干细胞移植治疗血栓闭塞性脉管炎：5年随访

背景：慢性缺血性疾病的长期疗效评估较短期疗效评估更为重要,关系患者远期生活质量及长期生存率。 目的：分析自体骨髓干细胞移植治疗血栓闭塞性脉管炎的5年随访结果。 方法：收集新疆医科大学第一附属医院血管甲状腺外科自2007年8月至2010年1月行自体骨髓干细胞移植的血栓闭塞性脉管炎患者43例。移植后1,2,3,4,5年电话定期随访疼痛、冷感、间歇性跛行距离,并观察患肢溃疡的变化情况。移植后1年复查患肢静脉血氧分压和血氧饱和度。 结果与结论：有完整随访资料的血栓闭塞性脉管炎患者38例进入结果分析。38例患者的疼痛、冷感、间歇性跛行情况较移植前明显好转,差异有显著性意义(Z值分别为-4.277、-5.086、-3.574,P < 0.001)。移植后1-5年间相比,患者的疼痛、冷感情况差异无显著性意义(P > 0.05),间歇性跛行距离逐渐增加,差异有显著性意义(Z=43.898,P < 0.001)。患肢静脉血氧分压和血氧饱和度移植前与移植后1年对比差异有显著性意义(t值分别为36.790、43.964,P值分别为0.040、0.037)。以上结果表明自体骨髓干细胞移植治疗血栓闭塞性脉管长期效果稳定。  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Pathology of bone marrow transplantation.

For evaluating the therapeutic approaches in the follow-up and complications of patients treated with bone marrow transplantation (BMT), the histopathology is important on many occasions. The authors describe the different morphological changes that have an important role for treatment of these patients, classified according to their target organs of localization: skin, digestive tract, liver, and bone marrow. Graft-versus-host disease (GVHD) mainly affects the skin, gastrointestinal tract, and liver, and is sometimes difficult to differentiate from radiochemotherapy or infectious diseases. In the liver, the most frequent complications are GVHD, veno-occlusive disease, and infections. In the bone marrow, it is most important to evaluate the elimination of hemopathy and the reconstitution of normal hematopoiesis.     

Autologous bone marrow transplantation as a treatment for autoimmune disease: mechanisms and results

Autoimmune diseases are characterized by immune response against self antigens. One of the current research interests in this field is oriented toward development of tolerance. One of the newest options in the search for tolerance is autologous bone marrow transplantation: a variant of bone marrow transplant in which the patient's own hematopoietic stem cells are reinfused after myeloablative therapy. The idea of using bone marrow transplant in treatment of autoimmune diseases derived from observing remission in autoimmune diseases in patients transplanted due to coexisting neoplastic disease. Although an isolated initial report of bone marrow transplant as treatment for autoimmune disease questioned the utility of this procedure, over all, results are encouraging. To compile information in a programmed and systematic manner, it is necessary to send more patients in all stages of immune diseases to specialized centers to be included in large multicenter randomized trials. In time, the role for this procedure in autoimmune diseases will become clear.     

自体髂骨植骨联合自体骨髓干细胞移植治疗骨折术后骨不连

BACKGROUND: Bone nonunion is a common complication in the orthopedic treatment, and its morbidity reached 5%-10%, which results in the long-term functional disturbance of the limbs, and even disability. Autogenous iliac crest graft has been commonly used to treat bone nonunion, but some limitations still exist. OBJECTIVE: To investigate the treatment outcomes of autogenous iliac crest graft combined with autologous bone marrow stem cell transplantation for bone nonunion after fracture surgery. METHODS: Clinical and follow-up data from 69 patients with bone nonunion were analyzed retrospectively. All patients were allotted to combination (n=37) and iliac (n=32) groups, followed by treated with autologous iliac crest graft combined with autologous bone marrow stem cell transplantation or  autologous crest graft, respectively. Afterwards, the hospitalization time, fracture healing time, bone mineral density and Fereadez-Esteve callus scores were detected and compared between groups. RESULTS AND CONCLUSION: The hospitalization time did not differ significantly between groups (P > 0.05). The fracture healing time in the combination group was significantly shortened compared with the iliac group (P < 0.05). The bone mineral density and Fereadez-Esteve callus scores in the combination group were significantly higher than those in the iliac group at 3 and 6 months after surgery (P < 0.05). The excellent and good rate of the affected limb function in the combination group was significantly higher than that in the iliac group (P < 0.05). These results suggest that autogenous iliac crest graft combined with autologous bone marrow stem cell transplantation for bone nonunion can accelerate fracture healing, promote porosis and improve the functional recovery of affected limbs. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

自体骨髓细胞移植联合高压氧治疗四肢骨不连

背景：骨折后由于多种原因所致骨不连是骨科常见的并发症,现有的治疗方法不能获得满意的疗效,寻找一种微创、安全有效的治疗方法成为国内外骨科学者研究的热点。 目的：观察自体骨髓细胞移植联合高压氧治疗四肢骨不连的临床疗效。 方法：常规消毒局部麻醉无菌操作下,抽取患者骨髓10-20 mL分离浓缩制备成骨髓细胞悬液2-4 mL;在C型X射线透视定位引导下,向骨不连处进行多点穿刺注射自体骨髓细胞浓缩液,局部压迫3-5 min后无菌包扎;骨髓细胞植入后即行高压氧治疗,10次为1个疗程,2个疗程之间间隔5 d,共治疗3个疗程。 结果与结论：37例骨不连患者愈合36例,疗效评定为优25例、良8例、可3例、差1例;骨痂出现时间平均为(7.22±1.96)周,骨折愈合时间平均为(7.91±1.79)个月;骨髓细胞植入后,无严重的并发症发生。说明采用自体骨髓细胞移植联合高压氧治疗骨不连,能够促进骨不连的愈合,是一种行之有效的治疗方法。     

经肝动脉途径兔自体骨髓干细胞移植治疗肝硬化

BACKGROUND:How to make more transplanted bone marrow stem cells stay and differentiate in the liver is an important issue, which is also crucial for treatment of liver cirrhosis via the hepatic artery. OBJECTIVE:To investigate the therapeutic effect of autologous bone marrow stem cell transplantation via the hepatic artery on liver cirrhosis. METHODS:Thirty New Zealand white rabbits were equivalently randomized into normal control, stem cell transplantation and model groups. Animal models of liver cirrhosis were made in the latter two groups. Then, model rabbits in the stem cell transplantation group were subjected to autologous bone marrow stem cell transplantation via the hepatic artery. Liver function of rabbits was detected in 1, 2, 4, 8, 10 weeks after cell transplantation, and pathological detection of the liver was performed in the 10th week. RESULTS AND CONCLUSION:At 10 weeks after cell transplantation, the liver function of the rabbits was improved significantly compared with the model group, including reduced activities of serum alanine aminotransferase, total bilirubin and aspartate aminotransferase, shortened activated partial thromboplastin time, and increased albumin level (P < 0.05). Pathological examination of the liver showed that the liver cells in the stem cell transplantation group were intact with no obvious edema and still had the structure of the pseudolobule, and compared with the model group, the degree of liver fibrosis was significantly reduced in the stem cell transplantation group. Our experimental results show that the transplantation of autologous bone marrow stem cells via the hepatic artery has a certain therapeutic effect on liver cirrhosis by increasing the body albumin content in a short time and improving the liver function.     

Autologous bone marrow transplantation in patients with acute nonlymphocytic leukemia, using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide

We studied 25 patients with acute nonlymphocytic leukemia in second remission (20 patients) or third remission (5 patients) in whom autologous bone marrow transplantation was performed with use of marrow incubated ex vivo with the alkylating agent 4-hydroperoxycyclophosphamide. Patients received intensive cytoreductive therapy with busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, followed by an infusion of marrow that had been collected in remission, treated with 4-hydroperoxycyclophosphamide, and cryopreserved. Four patients died from bacterial or fungal sepsis within the first month after transplantation, and one patient with persistent marrow hypoplasia died from gram-negative sepsis 155 days after infusion with autologous marrow. In the remaining patients, peripheral-blood levels of neutrophils in excess of 0.5 X 10(9) per liter and platelet counts over 50 X 10(9) per liter were attained at median intervals of 29 and 57 days after transplantation, respectively. Nine patients had leukemic relapses at 73 to 316 days (median, 182 days) after infusion of autologous marrow, for an actuarial relapse rate of 46 percent. Eleven patients (eight in second remission and three in third) remained in remission at a median of more than 400 days (range, greater than 230 to greater than 1653 days) after transplantation. The observed disease-free survival after transplantation with autologous marrow treated with 4-hydroperoxycyclophosphamide compares favorably with the results of syngeneic or allogeneic transplantation in similar groups of patients.     

Functional hyposplenism following allogeneic bone marrow transplantation.

AIMS--To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS--Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS--Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION--These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT.     

Problems of infection after bone marrow transplantation.

Representatives of 17 bone marrow transplant (BMT) teams met to discuss the problems of infection after BMT. With experience of more than 2200 transplanted patients over the past 10 yr, the changes in the patterns of infection were surprisingly similar. Deaths due purely to bacterial infection have greatly diminished and the major early problems today result from fungi and cytomegalovirus. The role of non-herpes group viruses has only recently received attention. With increasing numbers of survivors, late bacterial infections are assuming importance. The meeting also provided an opportunity to document the measures adopted to prevent infection during BMT and following discharge.     

Kinetics of erythrogenesis after bone marrow transplantation.

To determine the kinetics of bone marrow erythrogenesis after bone marrow transplantation, the authors counted reticulocytes (by blood smear and flow cytometry) and compared those data with neutrophil and platelet recovery in 23 consecutive bone marrow transplant patients. The earliest indication of marrow recovery after allogeneic and autologous bone marrow transplantation was defined as the second increasing cell count after the lowest recorded count, provided that the trend continued upward. Recovery of marrow function was detected earlier in 10 of 23 patients using reticulocyte counts than by either neutrophil or platelet count alone. Specifically, in 8 of these 10 patients, recovery of erythropoiesis was determined earlier by flow cytometric examination than by the blood smear method. On the other hand, combining the data using the earliest value of platelet, neutrophil, and reticulocyte counts indicated that the mean day of recovery in our patient population was determined to be 12.1 +/- 4 days after marrow infusion. In patients undergoing autologous and allogeneic bone marrow transplantation, serial neutrophil and reticulocyte count determinations are complementary in early clinical detection of successful engraftment.     

Histopathology of bone marrow reconstitution after allogeneic bone marrow transplantation

In order to study haematopoietic reconstitution in allogeneic bone marrow transplantation we investigated bone marrow histology in 61 biopsies of 37 patients, treated with HLA-compatible bone marrow grafts for leukaemia or severe aplastic anaemia. The biopsies were taken from the day of transplantation until 100 d after transplantation. Stromal changes, in particular oedema, fibrosis and granulomas, were found during the whole period of observation. These changes were more prominent in biopsies from leukaemia patients than from patients with aplastic anaemia. The cellularity in the biopsies increased until 28 d after bone marrow transplantation and was stable thereafter. Initially, only clusters of cells belonging to a single cell lineage were seen, suggesting that the first outgrowth of haematopoietic cells is by proliferation of committed precursor cells. Long-lasting abnormalities in localization of haematopoietic cells in the bone marrow space and of the myeloid: erythroid ratio were seen; dyserythropoiesis was common.     

自体骨髓单个核细胞移植治疗糖尿病下肢周围神经病变

背景：有研究表明移植骨髓单个核细胞治疗糖尿病下肢神经病变动物模型,通过在组织内能促进血管再生和增加血管生成因子及神经营养因子能改善临床症状。                             目的：观察自体骨髓单个核细胞移植治疗糖尿病下肢周围神经病变的临床效果。 方法：30例糖尿病下肢闭塞症患者60条下肢,按治疗方式的不同分为2组：自体骨髓单个核细胞移植的治疗组和对侧下肢非自体骨髓单个核细胞移植的对照组,各30条下肢。 结果与结论：移植4周后,治疗组总有效率高于对照组(P < 0.05)。两组治疗后神经病变自主症状问卷神经病变主觉症状问卷评分均较治疗前明显降低,治疗组评分降低更明显(P < 0.01),治疗组胫神经和腓总神经感觉和运动神经传导速度均较对照组快(P < 0.01),患者未出现并发症和不良反应。说明自体骨髓单个核细胞移植治疗糖尿病下肢周围神经病变的临床效果较好。