造血干细胞移植研究进展

造血干细胞移植(hematopoietic stem cell transplantation,HSCT)是通过化学药物及放射治疗清除患者的骨髓,再将健康供者的造血干细胞植入患者体内,建立新的造血系统及免疫系统,从而达到治愈血液系统恶性肿瘤及骨髓衰竭的目的.自从1981年我国开始第一例异基因造血干细胞移植(allo-HSCT)以来,经过20余年的努力,HSCT技术已取得很大进步,根据北京市道培医院移植中心统计结果,白血病标危组同胞人类组织相容性抗原(HLA)配型相合组5年生存率为80%,HLA半相合(单倍体)及非血缘造血干细胞移植组5年生存率为70%-75%,白血病高危组长期生存率为35%-40%.     

The 6th Annual Meeting of the UK Cord Blood and Adult Stem Cell Group

The meeting was established in 1999 by the UK cord blood immunobiology group. Over the last 6 years the annual meeting has attracted multidiscipline participants interested in the immunobiology of cord blood and the immunology of maternal fetal engraftment from universities, hospitals and cord blood banks throughout the UK and Europe. The 6th annual meeting was held in the Life Bioscience Centre ‘Centre for Life’ in association with the University of Newcastle upon Tyne. The purpose of this meeting was to bring together the most up-to-date scientific results, both the clinical applications and immunobiology of cord blood stem cells. The meeting, although relatively small-scale, was clearly focused on specific topics and was highly interactive between scientists and clinicians. The meeting was introduced and chaired by Professor Anne Dickinson, University of Newcastle upon Tyne, UK.     

The 6th annual meeting of the UK Cord Blood and Adult Stem Cell Group

The meeting was established in 1999 by the UK cord blood immunobiology group. Over the last 6 years the annual meeting has attracted multidiscipline participants interested in the immunobiology of cord blood and the immunology of maternal fetal engraftment from universities, hospitals and cord blood banks throughout the UK and Europe. The 6th annual meeting was held in the Life Bioscience Centre 'Centre for Life' in association with the University of Newcastle upon Tyne. The purpose of this meeting was to bring together the most up-to-date scientific results, both the clinical applications and immunobiology of cord blood stem cells. The meeting, although relatively small-scale, was clearly focused on specific topics and was highly interactive between scientists and clinicians. The meeting was introduced and chaired by Professor Anne Dickinson, University of Newcastle upon Tyne, UK.     

Targeting Cancer Stem Cells with Natural Killer Cell Immunotherapy

Introduction: Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with ‘stem-cell’ like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs).

Areas covered: Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. The authors review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs.

Expert opinion: Unlike cytotoxic cancer treatments, NK cells can target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells     

Peripheral Blood Stem Cell Mobilization and Engraftment after Autologous Stem Cell Transplantation with Biosimilar rhG-CSF

Introduction

Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen^®], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio^®, Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary.

Methods

In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 × 5 μg) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required.

Results

In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU^®, Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8–11 days) and 10 (8–12) days, respectively. Median time to platelet engraftment was 10.5 days (7–19 days). In Study 2, the patients’ median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9–27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 × 10⁶/kg (2.22–57.07 × 10⁶/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 × 10⁶/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients.

Conclusions

In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT.     

Safety Outcomes for Autologous Stem Cell Transplant in Multiple Myeloma

Systems have been put in place in the Mayo Clinic Stem Cell Transplantation program to reduce day-100 all-cause mortality. Currently our mortality has been reduced to 0.3%. Patients can undergo transplant as an outpatient, with a median hospital duration of 0 days and only 25% of patients requiring a hospital stay of 5 days or greater. Outpatient transplantation is safe and reduces patient-incurred costs.     

Multimodal Imaging Reveals Improvement of Blood Supply to an Artificial Cell Transplant Site Induced by Bioluminescent Mesenchymal Stem Cells

Purpose

An artificial site for cell or pancreatic islet transplantation can be created using a polymeric scaffold, even though it suffers subcutaneously from improper vascularisation. A sufficient blood supply is crucial for graft survival and function and can be enhanced by transplantation of mesenchymal stem cells (MSCs). The purpose of this study was to assess the effect of syngeneic MSCs on neoangiogenesis and cell engraftment in an artificial site by multimodal imaging.

Procedures

MSCs expressing a gene for luciferase were injected into the artificial subcutaneous site 7 days after scaffold implantation. MRI experiments (anatomical and dynamic contrast-enhanced images) were performed on a 4.7-T scanner using gradient echo sequences. Bioluminescent images were acquired on an IVIS Lumina optical imager. Longitudinal examination was performed for 2 months, and one animal was monitored for 16 months.

Results

We confirmed the long-term presence (lasting more than 16 months) of viable donor cells inside the scaffolds using bioluminescence imaging with an optical signal peak appearing on day 3 after MSC implantation. When compared to controls, the tissue perfusion and vessel permeability in the scaffolds were significantly improved at the site with MSCs with a maximal peak on day 9 after MSC transplantation.

Conclusions

Our data suggest that the maximal signal obtained by bioluminescence and magnetic resonance imaging from an artificially created site between 3 and 9 days after MSC transplantation can predict the optimal time range for subsequent cellular or tissue transplantation, including pancreatic islets.

     

脐血造血干细胞移植治疗地中海贫血

造血干细胞移植是目前唯一能治愈地中海贫血(地贫)的治疗方法.本文就脐血造血干细胞移植(Cord blood stem cell transplantation,CBT)的特点,CBT治疗地贫的临床研究和CBT治疗地贫的主要临床问题及对策作一综述.     

ABO血型不合的非清髓异基因外周血干细胞移植

为了探讨ABO血型不合对HLA相合的非清髓异基因外周血干细胞移植(NAST)的影响,回顾分析了15例ABO血型主要不舍,9例次要不合的HLA相合的NAST的临床特点,并选用同期ABO血型相合的NAST作成组比较。结果显示：24例ABO血型不合的NAST受者在输入供者外周血千细胞悬液时无1例发生急性溶血,但有2例发生迟发性溶血。统计学分析表明,ABO血型不合对NAST骨髓植活、血小板恢复、GVHD、疾病复发及无病生存均无影响。在ABO血型主要不合组,红系开始恢复时间明显延迟,其中1例“0”型血受者发生纯红细胞再生障碍,持续5个月。结论：ABO血型不合不是NAST的障碍,仅在ABO血型主要不合时．红系恢复时间延迟。     

Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients

This study explored the pharmacokinetics and the pharmacodynamics of continuous-infusion meropenem in a population of pediatric hematopoietic stem cell transplant (HSCT) patients who underwent therapeutic drug monitoring. The relationship between meropenem clearance (CL_M) and estimated creatinine clearance (CL_CR) was assessed by nonlinear regression. A Monte Carlo simulation was performed to investigate the predictive performance of five dosing regimens (15 to 90 mg/kg of body weight/day) for the empirical treatment of severe Gram-negative-related infections in relation to four different categories of renal function. The optimal target was defined as a probability of target attainment (PTA) of ≥90% at steady-state concentration-to-MIC ratios (C_SS/MIC) of ≥1 and ≥4 for MICs of up to 8 mg/liter. A total of 21 patients with 44 meropenem C_SS were included. A good relationship between CL_M and estimated CL_CR was observed (r² = 0.733). Simulations showed that at an MIC of 2 mg/liter, the administration of continuous-infusion meropenem at doses of 15, 30, 45, and 60 mg/kg/day may achieve a PTA of ≥90% at a C_SS/MIC ratio of ≥4 in the CL_CR categories of 40 to <80, 80 to <120, 120 to <200, and 200 to <300 ml/min/1.73 m², respectively. At an MIC of 8 mg/liter, doses of up to 90 mg/kg/day by continuous infusion may achieve optimal PTA only in the CL_CR categories of 40 to <80 and 80 to <120 ml/min/1.73 m². Continuous-infusion meropenem at dosages up to 90 mg/kg/day might be effective for optimal treatment of severe Gram-negative-related infections in pediatric HSCT patients, even when caused by carbapenem-resistant pathogens with an MIC of up to 8 mg/liter.     

经皮自体骨髓干细胞移植治疗骨不连的临床研究

目的探讨经皮自体骨髓干细胞移植治疗骨不连的疗效。方法将140例骨不连患者分为自体骨移植组(A组)70例及自体骨髓干细胞移植组(B组)70例,经手术治疗,并行简单有效内外固定。结果A组2个月42例(60%)骨折端周围有少量新生骨痂,5个月46例有大量骨痂形成;B组2个月60例骨折端周围有大量新生骨痂,5个月45例有连续骨痂形成。A组平均愈合时间(8.4±1.8)个月,B组平均愈合时间(6.5±2.0)个月,两组间有显著性差异(P<0.05)。治疗期间无明显不良反应。结论经皮自体骨髓干细胞移植较传统植骨治疗骨不连有明显优势。