Age does not matter: Mobilization and harvesting are safe and effective for elderly allogeneic peripheral hematopoietic stem cell donors

It took several years to succeed safe hematopoietic stem cell transplantations. HLA-matched unrelated donors have become the most common donor source for allogeneic hematopoietic stem cell transplants worldwide. The sibling donor may have more comorbidity and decreased regenerative potential of stem and immune cells. The purpose of this retrospective study was to examine whether aging had any negative effect on aging donor or patient. 27 patients who received a hematopoietic stem cell transplantation (HSCT) from February 2013 to May 2016 and their donors were analyzed. We showed that transplantation from older relative donor was feasible. Adverse event rate was low. Donors tolerated the procedure very well. Good CD34+ cell harvest was possible.     

诱导多潜能性干细胞的研究现状与临床应用前景

胚胎干细胞可作为细胞替代治疗中很好的供体细胞来源.但由于伦理学的原因,限制了胚胎干细胞在细胞替代治疗中的应用前景,而诱导多潜能性干细胞（induced pluripotent stem cell,iPS细胞）的出现则提供了一种替代胚胎干细胞的多潜能性细胞.因为iPS细胞的建立不需要卵细胞,也不破坏发育中的胚胎,所以iP...     

Young child as a donor of cells for transplantation and lymphocyte based therapies

In most cases of hematopoietic cell transplantation (HSCT) in pediatric recipient, the priority is given to bone marrow as a hematopoietic cell (HSC) source. The same expectations should be given to pediatric sibling donor. Bone marrow (BM) harvest is a standard method of HSC collection in pediatric siblings, however peripheral blood HSC (PBSC) collection is safe in healthy pediatric donors, and target hematopoietic cell yields can be achieved. Bone marrow or peripheral blood cell collection, both hematopoietic cells and lymphocytes, in pediatric sibling donors is safe, however there is a small risk of severe adverse events (SAE); still the risk of SAE is lower in children than in adults. The early adverse effects (AE) both after BM and PBSC collection are mild, short-term and easy to prevent or control, however they can occur in a relatively large proportion of donors. The risk of mild AE is lower in children than in adults, except PBSC collection in children <20?kg, who might be at risk of various complications. Short-term G-CSF administration and PBSC collection in pediatric donors is safe. No data exist on long-term adverse effects of short-term G-CSF course. Pediatric donors and their parents must be informed about the risk of possible complications.     

Hematopoietic cell transplantation for sickle cell disease: state of the art

Sickle cell disease is associated with considerable morbidity and premature mortality. Hematopoietic cell transplantation offers the possibility of cure and is associated with excellent results in pediatric patients receiving stem cell transplantation from a matched sibling donor. A reduced-intensity conditioning regimen has the potential to further reduce regimen-related morbidity and mortality. Improved understanding of the natural history of complications, such as stroke and pulmonary hypertension, effects of treatments such as hydroxyurea and blood transfusions, as well as the impact of transplantation on organ damage, are likely to influence the timing and indication of transplantation. Improvements in preparative regimens may enable the safe use of an alternative source of stem cells, such as unrelated matched donors, and further improve the applicability and acceptability of this treatment.     

Evaluation and eligibility of HLA-identical sibling donors for stem cell/bone marrow donation

Overall, the number of allogeneic transplants performed world-wide has not increased dramatically over the past 5 years. However, the proportion of allogeneic transplants undertaken using peripheral blood progenitor cells (PBPCs) has risen significantly. Currently, as part of an ethically approved trial, potential donors are seen, assessed and consented by physicians not caring directly for the recipients. Thirty-five potential sibling donors were seen and assessed for their willingness and fitness to donate for 28 patients. One donor opted to give bone marrow and the rest selected PBPC donation. Seven of these donors were found to have concurrent medical conditions. Due to poor venous access, one donor was advised to donate bone marrow and two others donated bone marrow due to an underlying condition. Four others were deemed unfit for donation. Donation of stem cells from bone marrow or peripheral blood is not a risk-free procedure; careful preassessment and counselling is mandatory especially when the age of prospective patients and therefore donors is increasing.     

Having a sibling as donor: Patients' experiences immediately before allogeneic hematopoietic stem cell transplantation

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of diseases but is also associated with significant risks. With HSCT the donor is either a relative, most often a sibling, or an unrelated registry donor.PurposeThe aim was to explore patients' experiences, immediately before transplantation, regarding having a sibling as donor.MethodTen adult patients with sibling donors were interviewed before admission for HSCT. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis.ResultsThe main theme Being in no man's land is a metaphor for the patients' complex situation with its mixture of emotions and thoughts prior to transplantation. The three subthemes Trust in the sibling donor, Concern about others and Loss of control cover the various experiences. The patient's experiences are influenced by their personal situation and the quality of the relationship with the sibling donor. While patients feel secure in having a sibling donor, they are dependent for their survival on the cell donation and feel responsible for the donor's safety during donation. These emotions intensify the patients' sense of dependency and loss of control.ConclusionsIn caring for HSCT patients the nurses should be aware of the complexity of the patients' situation and keep in mind that having a sibling donor might imply extra pressure, including a sense of responsibility. Caring for both patients and sibling donors optimally is a challenge, which needs further improvement and exploration.     

Old is bad? The effect of age on peripheral stem cell mobilization and transplantation outcomes

IntroductionAllogeneic stem cell transplantation (Allo-SCT) is a well-established treatment option for hematological malignancies. With the introduction of reduced-intensity conditioning regimens (RIC) and better supportive measures the elderly are able to receive Allo-SCT. A considerable number of patients are elderly, and often their HLA matched sibling donor is elderly, moreover. Here, we aim to explore the effect of donors’ age on stem cell harvesting, engraftment duration after Allo-SCT, and product quality.MethodSixty-one healthy allogeneic stem cell donors aged 50 years and older who underwent stem cell mobilization at our center between 2009–2019 were enrolled for the study. All donors received 4–5 days of G-CSF, mostly filgrastim or lenograstim and their biosimilar equivalents were given subcutaneously as a total dose of 10 mcg/kg/day. Groups were separated into three groups as aged 50–54 group A, 55–59 group B, aged 60 and older group C.ResultsPre-apheresis peripheral blood CD34+ count was similar all groups (p = 0.2). One day apheresis was sufficient for 72.7 % of group A, 27.3 % for group B and 47.1 % for group C (p = 0.02). Total harvested CD34+ cells were comparable among groups (p = 0.5).ConclusionAdequate stem cell harvest in older donors is feasible. Older donors may require more than one apheresis procedure and generally procedure was well tolerated. When assessing donors, age should represent less significance.     

Allogeneic peripheral blood stem cell collection as of 2008.

The rapid growth of the use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize and collect allogeneic peripheral blood stem cells (PBSCs) for transplantation has made it a new international standard. While the procedure remains safe, older donors, donors with significant comorbidities and pediatric donors are now often employed. This brings a new set of challenges in the donor evaluation, medical clearance, informed consent and collection process. Rare and unexpected severe adverse events related to rhG-CSF administration and PBSC apheresis have been described. Proper PBSC donor counseling, evaluation and care have become even more important.     

Bone marrow as a source of hematopoietic stem cells for human gene therapy of β-thalassemia

β-Thalassemia is a severe inherited anemia caused by insufficient production of β-globin chains. Allogeneic hematopoietic stem cell (HSC) transplantation is currently the only cure, and is limited by donor availability and regimen-related toxicity and mortality. Gene therapy is a promising therapeutic tool for all thalassemic patients lacking a compatible donor and potentially provides transfusion independence in the absence of transplant-related complications, such as graft rejection and graft-versus-host disease. The issue of HSC procurement is critical in this setting because of the specific features of thalassemic syndromes, which include bone marrow (BM) expansion, ineffective erythropoiesis, and splenomegaly. Little is known about the efficiency of CD34(+) cell yield from steady-state BM harvests from thalassemic patients. We have collected data on safety and cell yield from 20 pediatric patients with β-thalassemia who underwent autologous BM harvest before allogeneic HSC transplantation, and from 49 age-matched sibling donors who also underwent BM harvest. The procedure was safe, as no significant adverse events occurred. In terms of cell yield, no difference was found between patients and normal donors in the number of CD34(+) cells and total nucleated cells harvested. Most importantly, no difference was found in the proportion of myeloid and erythroid progenitors, suggesting a similar repopulating capacity. On the basis of these results, we conclude that steady-state BM can be used as a safe and efficient source of HSC for gene therapy of β-thalassemia.     

心脏死亡器官捐献供者家属应对压力的探讨

目的：探讨压力理论对心脏死亡器官捐献供者家属面临的伦理问题的指导性意义,缓解供者家属焦虑状态,争取可供移植器官的来源。方法收集我院54例潜在捐献者资料,分析捐献者家属心理压力的来源,探讨压力理论对缓解压力,加强供者家属对伦理问题应对的作用。结果54例潜在捐献者中同意捐献者35例,成功捐献22例。结论压力理论可应用于今后心脏死亡器官捐献供者家属管理中,为争取更多可移植器官提供保障。     

Recent advances in cord blood stem cell transplantation

Cord blood stem cells are recognized as alternative donors for patients without HLA matched sibling donors in allogeneic stem cell transplantation, while limited number of stem cells are still associated with delayed or failed engraftment. To overcome this issue, clinical trials including reduced-intensity conditioning, double units transplantation, intrabone marrow injection as well as infusion of ex vivo expanded regulatory T cells have been performed. Chimerism analysis by multicolor flow cytometry is also valuable in monitoring the engraftment process. Future studies will test the potential application of cord blood stem cells to non-hematological disorders.     

Unrelated donor transplantation after reduced intensity conditioning as an approach for patients lacking related donors for allogeneic stem cell transplantation

Allogeneic stem cell transplantation (SCT) after reduced intensity conditioning (RIC) provides a new curative treatment option for patients usually not eligible for allogeneic SCT. Because the majority of patients lack HLA-identical sibling donors (SD), unrelated donor (UD) transplantation is performed increasingly. In this retrospective analysis, we have reviewed our experience with reduced-intensity conditioning regimens, comparing related and unrelated donors. From November, 1997, to February, 2002, 51 patients with hematological malignancies received allogeneic SCT after various RIC regimens. A total of 31 had a related donor, and the remaining 20 had an unrelated donor (UD). Both groups were comparable with respect to age and gender. We observed a trend toward higher rate of graft failure in the unrelated donor group with 11% compared to 3% in the related donor group (p = 0.55). The rate of acute graft-versus-host disease (GVHD) II-IV was 36% in the RD group versus 44% for the UD group; severe GVHD III-IV occurred in 26% and 22%, respectively. There were more serious infections in the unrelated donor group with 25% compared to 16%. Transplant-related mortality was 13% (RD group) versus 30% (UD group). At 21 months, progression-free survival was 30% in both groups. The Kaplan Meier estimate of overall survival was 40% (RD) and 30% (UD group). In summary, we found no statistically significant difference regarding progression free and overall survival, despite a trend for more graft failure and increased transplant-related complications associated with the use of stem cells from unrelated donors.     

The effect of age on peripheral stem cell mobilization in healthy donors,single center experience

Purpose : Peripheral stem cell transplantation is used as a life‐saving therapeutic option in hematological malignancies. As previously established, most hematological malignancies are seen in the elderly population. Therefore, possible HLA‐identical sibling donors of elderly patients are generally of an advanced age. In this study, we aimed to evaluate the effect of old age on stem cell mobilization and quality in older adult healthy sibling donors. Materials and Methods : Between 2006 and 2014, we evaluated 38 healthy donors aged ≥55 years. The granulocyte‐colony stimulating factor (G‐CSF) analogs were used at a dose of 5 µg/kg/day and administered subcutaneously twice a day for five days. CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. The National Marrow Donor Program selects healthy unrelated donors if they are younger than 60 years. Therefore, we compared the product quality in donors over the age of 60 to that in donors aged 60 years or less. Results : We collected sufficient products from all the donors with one to three apheresis procedures. No serious complication was detected in all donors. Reaching the target CD34+ cell count in one day were detected in 83% of younger and 79% of older donors (P = NS). Collected CD34+ cells x10e6/recipient body weight (kg) was same and 5.1 in the groups (P = NS). There were no correlation between the donor age and these parameters. Conclusion : Healthy donor apheresis in older adults can be performed effectively and possible donors should be evaluated regardless of their age. J. Clin. Apheresis 32:16–20, 2017. © 2016 Wiley Periodicals, Inc.     

The bioethics of stem cell research and therapy

Discussion of the bioethics of human stem cell research has transitioned from controversies over the source of human embryonic stem cells to concerns about the ethical use of stem cells in basic and clinical research. Key areas in this evolving ethical discourse include the derivation and use of other human embryonic stem cell–like stem cells that have the capacity to differentiate into all types of human tissue and the use of all types of stem cells in clinical research. Each of these issues is discussed as I summarize the past, present, and future bioethical issues in stem cell research.The main bioethical issues associated with human stem cells involve their derivation and use for research. Although there are interesting ethical issues surrounding the collection and use of somatic (adult) stem cells from aborted fetuses and umbilical cord blood, the most intense controversy to date has focused on the source of human embryonic stem (hES) cells. At present, new ethical issues are beginning to emerge around the derivation and use of other hES cell–like stem cells that have the capacity to differentiate into all types of human tissue. In the near future, as the stem cell field progresses closer to the clinic, additional ethical issues are likely to arise concerning the clinical translation of basic stem cell knowledge into reasonably safe, effective, and accessible patient therapies. This Review summarizes these and other bioethical issues of the past, present, and future of stem cell research.     

应用寡聚核苷酸芯片检测白血病与其同胞供者的白血病基因表达差异

为了应用寡聚核苷酸基因表达谱芯片研究9对白血病患者／同胞供受者对之间的基因表达谱差异以识别主要的疾病相关基因，将163条白血病／肿瘤发病相关基因组群列入芯片设计，合成寡核苷酸探针，用点样仪点片制成基因芯片。提取病初白血病患者及其供者的骨髓／外周血标本或其相对应的健康同胞供者经G-CSF动员后并经CS-3000细胞分离机采集的浓集的9份外周血造血干细胞的总RNA；分别逆转录并进行寡核苷酸探针杂交。结果表明：与其相应的正常供者配对比较，发现4例ALL患者中存在6条显著差异表达基因，其中上调表达基因5条(RIZ，STK-1，T—cell leukemia／lymphoma 1A，Cbp／p300，Opl8)，下调表达1条(hematopoietic proteoglycan core protein)；5例AML-M4和AML-M，患者中亦存在7条显著差异表达基因，其中上调表达6条(STAT5B，ligand p62 for the Lck SH2，CST3，LTC4S，myeloid leukemia factor 2，epb72)，下调表达1条(CCR5)。结论：选择有高度遗传关联的兄弟姐妹供受者对作为差异研究比照对象，利用寡聚核苷酸基因芯片技术进行疾病基因的筛查，筛查出了13条主要异常基因；进一步确认了上述基因在白血病分子发病机制中的关键性作用。     

胚胎干细胞研究的伦理和心理学问题

背景：胚胎干细胞研究具有重要的医学价值,在基因治疗、组织工程学、药学等许多领域都具有广泛的应用,使人们看到了治疗疾病的新希望,而其相关研究成果也引发了许多伦理和心理学问题。目的：综述目前胚胎干细胞研究中的伦理和心理学问题。方法：应用计算机检索2001-01/2010-12PubMed数据库、维普数据库及万方数据库有关干细胞研究产生的伦理和心理学问题相关文献,英文检索词＂embryonicstemcells,morality,psychological＂,中文检索词＂胚胎干细胞,伦理学,心理学＂。检索文献量总计122篇,最终纳入符合标准的文献33篇。结果与结论：胚胎干细胞究中伦理学问题的焦点主要包括：干细胞来源的伦理学问题,干细胞＂克隆＂的伦理学问题,干细胞与生命的伦理学问题,干细胞研究存在和需要解决的问题及干细胞研究中伦理学规范问题。干细胞研究中的心理学问题主要是人们对干细胞研究特别是＂克隆＂技术的认识。相关研究多涉及造血干细胞移植患者的心理变化。胚胎干细胞的研究目前已取得了突破性成果,给医疗、卫生健康等方面带来了革命性影响。     

异基因造血干细胞移植治疗儿童再生障碍性贫血临床分析

目的探讨异基因造血于细胞移植治疗儿童再生障碍性贫血（简称再障）的疗效。方法6例再障患儿中,5例行G．CSF动员的HLA全相合同胞供体骨髓联合外周血造血干细胞移植,平均输入骨髓单个核细胞数4．61（1．5～13．2）×10^8／kg,平均输入外周血单个核细胞数9．36（2．05～16．75）×10^8／kg。预处理方案采用FLU＋CTX＋ATG。1例实行无关供体HLA全相合骨髓移植,输入骨髓单个核细胞数16．8×10^8／kg。预处理方案采用FLU＋CTX＋TBI。急性GVHD预防均采用CSA＋MTX。结果1例移植失败,未植入,移植后第23天自体造血功能恢复。余5例均植入。所有患者均无GVHD的发生。1例病史4年的轻型再障患儿在移植后1年4个月时移植排斥,再障复发合并重症感染治疗无效死亡;余5例随访至2009年2月均无病存活。结论HLA全相合的同胞间骨髓联合外周血造血干细胞移植可作为治疗儿童再障的首选治疗方法;免疫抑制治疗失败且无合适同胞供者的再障患儿可以选择无关供体HLA全相合骨髓移植。     

Toward 'SMART' stem cells

Stem cell research is at the heart of regenerative medicine, which holds great promise for the treatment of many devastating disorders. However, in addition to hurdles posed by well-publicized ethical issues, this emerging field presents many biological challenges. What is a stem cell? How are embryonic stem cells different from adult stem cells? What are the physiological bases for therapeutically acceptable stem cells? In this editorial review, I will briefly discuss these superficially simple but actually rather complex issues that surround this fascinating cell type. The goal of this special issue on stem cells in Gene Therapy is to review some fundamental and critical aspects of current stem cell research that have translational potential.     

Comparison of allogenic stem cell transplantations performed with frozen or fresh stem cell products with regard to GVHD and mortality

PurposeStem cells are collected from donors and infused to the recipient in allogenic peripheral stem cell transplantations. The use of frozen stem cells can promote donor compatibility, and overcoming possible problems due to insufficient stem cell mobilization will also be easier.Nevertheless, studies about the use of frozen peripheral stem cells in allogenic transplantation are extremely rare. In this study, we aimed to compare the clinical outcomes of allogenic stem cell transplants from frozen or fresh stem cell products.Materials and methodsThis retrospective analysis was conducted between April 2004 and September 2018 in the bone marrow transplantation unit of Ankara Numune Training and Research Hospital. Clinical data of patients who received allogenic peripheral stem cell transplantations from fully matched sibling donors were compared for 42 fresh and 30 frozen stem cell transplants.ResultsWhile the platelet engraftment period, febrile neutropenia period, hospitalization period, and 100-day mortality rates did not show any differences, the neutrophil engraftment period was longer in the frozen group (mean: 14 days vs. 16 days, p = 0.006). Acute and chronic graftversus-host disease (GVHD) rates were similar in both groups; however, the rate of grade 3 or4 chronic liver GVHD was slightly higher in transplants performed with fresh stem cells compared to the frozen group (p = 0.046). Overall survival was similar between the groups (p = 0.700).ConclusionThe use of frozen peripheral stem cells in allogenic stem cell transplantation may be a reasonable option that can be applied without causing a significant change in clinical results.     

The psychosocial aspects of donating blood stem cells: the sibling donor perspective

The collection of peripheral blood progenitor cells (PBPC) by apheresis has become common in related allogeneic donors. However, the acceptability of the procedure to donors has not been documented. The purpose of this baseline case series study was to evaluate the psycho-social dimensions of apheresis from the perspective of healthy sibling donors and to explore issues surrounding fully informed consent including voluntary donation. At the first interview to discuss donation, 17 consecutive human leucocyte antigens (HLA) identical sibling donors who chose to donate PBPC were recruited to the study. They then completed both scales of the State-Trait Anxiety Inventory. The state scale was completed again immediately before first apheresis. At the end of the final apheresis, the donors were interviewed again by an independent researcher using a standardised questionnaire. All aspects of the procedure were well tolerated, including levels of anxiety and pain. Donors donated even if the relationship with their sibling was poor. However, some areas for improvement were highlighted. Eight (47%) donors were asked to donate by their sibling or another close relative, and this gave them no real volunteer status. Written information was judged important by 11 (65%) donors, but the material used was limited. The possibility of a poor outcome for the recipient was not well understood. The content of the written documentation and the management of confidentiality in terms of donor volunteer status needed to be addressed. A further study regarding the follow-up needs of donors, including those where the outcome is poor, is underway.