Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation

BACKGROUND: Cytomegalovirus (CMV) disease constitutes a serious complication after allogeneic stem cell transplantation. For the clearance of CMV, CD8+ T cells are pivotal. STUDY DESIGN AND METHODS: Here, the novel streptamer technology was used at good manufacturing practice (GMP) level for adoptive transfer of CMV‐specific T cells into acute leukemia patients with recurrent high CMV antigenemia after allogeneic stem cell transplantation. RESULTS: After a single transfusion, the frequency of CMV‐specific CD8+CD45RA+CCR7– effector T cells increased dramatically from 0.0% to a maximum of 27.1% of all T cells. These T cells were clearly donor derived and did not stem from intrinsic reconstitution, as demonstrated by analysis of 1) donor chimerism through single‐tandem repeats, 2) T‐cell receptor excision circles, and 3) Vβ‐chain typing by polymerase chain reaction. Clinically, the specific T‐cell transfer resulted in a persistent clearance of the CMV antigenemia, which allowed the patients to discontinue toxic antiviral drug therapy without further high‐level reactivation of CMV, demonstrating the power of the streptamer technology. CONCLUSION: Taken together, the streptamer technology offers the advantage of selecting virus‐specific CD8+ T cells at GMP level for adoptive T‐cell transfer, thus inducing long‐lasting specific CD8+ T‐cell responses without increasing the risk for graft‐versus‐host disease.     

Osteopenia and osteoporosis in pediatric patients after stem cell transplant.

As more patients are surviving the transplant experience, more children are coping with long-term side effects. Long-term side effects, such as osteopenia and osteoporosis, are not as well acknowledged in pediatric stem cell transplant survivors. Osteopenia and osteoporosis can lead to fractures, deformities, pain, and financial burden. There are many factors during and after a stem cell transplant that cause patients to be at an increased risk for osteopenia or osteoporosis. Nurses have the ability to prevent these potentially debilitating and progressive diseases and to provide adequate treatment to prevent further complications. Key features of the history, physical examination, and diagnostic imaging can assist with making a diagnosis of osteoporosis or osteopenia. Prevention of osteopenia and osteoporosis involves both lifestyle modifications and medical management. Measures to prevent and treat bone loss are crucial. Transplant nurses must be knowledgeable regarding the risk factors and prevention and treatment strategies for osteopenia and osteoporosis.     

Psychosocial factors predicting survival after allogeneic stem cell transplant

Purpose

A primary aim was to assess the relative contribution of psychological factors, such as anxiety, depression and mental adjustment to cancer, to overall survival outcomes at a median follow-up of 2 years following allogeneic haematopoietic stem cell transplant (HSCT). A secondary aim was to ascertain if demographic, medical and psychosocial factors assessed prior to transplantation were predictors of survival for patients after accounting for post-transplant events.

Method

Between 2005 and 2011, 130 allograft patients completed the Mental Adjustment to Cancer Scale and Brief Symptom Inventory-18 as part of routine psychological assessment before undergoing transplantation. Survival status data were obtained, and predictors of survival status assessed and analysed using Cox-regression models.

Results

Thirteen percent experienced clinical levels of distress pre-transplant. None of the psychological factors predicted post-HSCT survival. In contrast, hierarchical multivariate analysis indicated that post-transplant factors (acute graft-versus-host disease and relapse post-transplant) predicted survival (Chi-square change, p?<?0.001). The addition of a series of pre-transplant psychosocial and medical variables further improved the prediction of survival (Chi-square change, p?=?0.01). In particular, relationship status (being single) (p?=?0.04) and increased somatic symptoms (p?=?0.02) pre-transplant were associated with shorter survival. Both variables were not associated with medical factors but were related to increased severity of anxiety and depressive symptoms as well as greater use of helpless-hopelessness and reduced fighting spirit adjustment response.

Conclusions

Despite the significant influence of acute post-transplant factors in predicting survival following allogeneic HSCT, multidisciplinary pre-transplant assessments are important in identifying patients who are likely to experience poorer survival outcomes.     

造血干细胞移植患者实施不同肛周护理方法的效果观察

目的探讨造血干细胞移植患者实施不同肛周护理方法的满意度及成效。方法将2006年2月至2008年2月入住传统移植病房患者62例作为对照组,2009年1月至2010年2月入住有全自动无水箱坐便器卫生间的新型无菌病房100例患者作为观察组,比较两组病例肛周护理方法满意度及肛周感染发生率。结果人住新型无菌病房患者实施改进的肛周护理方法满意度〉95％,两组患者的肛周感染率比较差异无统计学意义（P〉0．05）。结论入住有全自动无水箱坐便器卫生问的新型无菌病房的患者应用改进的肛周护理方法既能满足患者人性化的需求,提高了患者的满意度,也能有效预防肛周感染的发生,提高了患者的舒适度及护理的安全度。     

Transient anti rhesus alloantibody produced by graft after non-myeloablative allogeneic stem cell transplant.

BACKGROUND: We report the case of a patient who received an allogeneic transplant with peripheral blood compatible ABO, Rhesus mismatched progenitor cells and who developed an asymptomatic transient anti Rhesus alloimmunisation. CASE REPORT: A 56-year-old man with renal cell carcinoma received a non-myeloablative allogeneic PBPC ABO compatible graft from his HLA-identical brother. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. On day + 59, prior to any transfusion, a positive direct antiglobulin test (IgG++, C3d-) was detected. The indirect antiglobulin test (IAT) was considered doubtful, and IAT identification revealed the presence of an active anti Rhesus antibody (anti D specificity) in the patient's serum. This immunisation had no clinical consequence, with no acute hemolytic episode. Further monitoring showed negative antibody screening tests on day + 78. CONCLUSION: To our knowledge this is the first reported case of transient anti Rh (D) allo-immunisation after non-myeloablative allogeneic peripheral blood progenitor cell (PBPC) transplant. The period of occurrence and the specificity of this antibody strongly suggest a donor cell origin.     

异基因造血干细胞移植患者的出院指导

目的：探讨异基因造血干细胞移植后正确的出院指导。方法：心理指导：帮助他们重建生活信念,恢复家庭关系;帮助患者了解药物副作用和逐渐减量方法;自身护理的指导：HSCT破坏了人体免疫机制,需要特别注意个人卫生;饮食指导：饮食应给予易消化、营养丰富的清淡的、新鲜食物;活动的指导：活动量的大小要依据血象恢复情况和个人身体状况而定。结果：经有效的出院指导,患者及家属都基本掌握了相关知识。结论：出院指导是促进患者康复,提高患者生活质量的有效方法。     

Complications and risks in hematopoietic stem cell transplant patients.

Hematopoietic stem cell transplantation is a recognized treatment for hematological diseases such as leukemia and lymphoma, certain solid organ tumors, and a limited number of immunologic disorders. The major risks associated with this procedure are infections and development of graft-vs-host disease. Bacterial or viral agents are the most common cause of infections, but fungal and protozoan organisms may also be isolated. Bacterial infections occur most frequently in the first 30 days after transplant, whereas the onset of viral infections usually occurs later during the first three months posttransplant. Studies have demonstrated that there are a variety of predisposing factors that influence the type of infection a patient develops. These include underlying disease, type of chemotherapy regimen, type of antimicrobial and antiviral regimen, presence of graft-vs-host disease, and period of severe neutropenia posttransplant. Of these, the period of neutropenia appears to be the most significant. Graft-vs-host disease is seen in those patients who have received allogeneic hematopoietic stem cell transplants. New antimicrobial and antiviral agents and manipulation of the hematopoietic stem cell transplant to select specific cell types for infusion have provided some methods to prevent or decrease the number and severity of infections or to prevent/control graft-vs-host disease.     

碘附药浴用于造血干细胞移植患者体表皮肤消毒的效果

目的 比较氯己定药浴与碘附药浴两种方法用于造血干细胞移植患者体表皮肤消毒的效果.方法 将造血干细胞移植患者随机分为对照组和实验组各50例,对照组用0.05%氯己定溶液剂,药浴时间30min;实验组用0.05%碘附溶液剂,药浴时间15 min,两组水温42～44 ℃,观察右腋下、右外耳道、右鼻腔、脐周、右腹股沟、肛门共6个部位药浴后的病原菌数;眼部不适感例数;皮肤干燥发痒例数;药物刺激性呛咳例数;药浴溶液水温变化情况.结果 两组患者药浴后病原菌数阳性率比较差异无统计学意义（P＞0.05）;在眼部酸胀,眼部不适感;皮肤干燥发痒;药物刺激性呛咳方面差异有统计学意义（P＜0.05）;两组患者药浴15min和药浴30min时水温下降有显著性差别.结论 碘附药浴较氯己定药浴缩短了药浴时间,水温下降程度小,减轻了患者药浴的不适感,提高了舒适度.     

Gene transfer mediated by stem cell grafts to treat CNS injury

Introduction: Stem cell transplantation holds promise for promoting anatomical repair and functional recovery after traumatic or ischemic injuries to the CNS. Harnessing stem cells with therapeutic genes of interest is regarded as an attractive approach to augment therapeutic benefits of stem cell grafts.

Areas covered: The advantage of stem-cell-mediated gene transfer is the engraftibility of stem cells that can ensure a long-term and stable expression of therapeutic genes. In addition, stem-cell–gene interaction may synergistically amplify therapeutic benefits. Delivery of classical neurotrophic factor genes provided neuroprotective and pro-regenerative effects in various injury models. Some studies employed therapeutic genes targeting post-injury microenvironment to support endogenous repair. Recent trials of stem-cell-mediated transfer of nonclassical growth factors showed relatively novel biological effects. Combinatorial strategies seem to have the potential to improve therapeutic efficacy.

Expert opinion: Future development of induced pluripotent stem cells and novel scaffolding biomaterials will greatly expedite the advances in ex vivo gene therapy to treat CNS injury. Before moving to a clinical stage, rigorous preclinical evaluations are needed to identify an optimal gene or gene combination in different injury settings. Improving the safety of viral vectors will be a critical prerequisite for the clinical translation.     

Gene transfer mediated by stem cell grafts to treat CNS injury

INTRODUCTION: Stem cell transplantation holds promise for promoting anatomical repair and functional recovery after traumatic or ischemic injuries to the CNS. Harnessing stem cells with therapeutic genes of interest is regarded as an attractive approach to augment therapeutic benefits of stem cell grafts. AREAS COVERED: The advantage of stem-cell-mediated gene transfer is the engraftibility of stem cells that can ensure a long-term and stable expression of therapeutic genes. In addition, stem-cell-gene interaction may synergistically amplify therapeutic benefits. Delivery of classical neurotrophic factor genes provided neuroprotective and pro-regenerative effects in various injury models. Some studies employed therapeutic genes targeting post-injury microenvironment to support endogenous repair. Recent trials of stem-cell-mediated transfer of nonclassical growth factors showed relatively novel biological effects. Combinatorial strategies seem to have the potential to improve therapeutic efficacy. EXPERT OPINION: Future development of induced pluripotent stem cells and novel scaffolding biomaterials will greatly expedite the advances in ex vivo gene therapy to treat CNS injury. Before moving to a clinical stage, rigorous preclinical evaluations are needed to identify an optimal gene or gene combination in different injury settings. Improving the safety of viral vectors will be a critical prerequisite for the clinical translation.     

Parental caregiving of children prior to hematopoietic stem cell transplant

Using the Caregiver Reaction Assessment (CRA), we assessed positive reactions and burdens of the caregiving experience among parental caregivers (n = 189) of children scheduled to undergo hematopoietic stem cell transplant. Although widely used in non-parental caregivers, the CRA has not been used in parents of pediatric patients. Reliability (Cronbach's alpha: .72-.81 vs. .63) and concurrent validity (correlation: .41-.61 vs. .28) were higher for negatively framed than positively framed subscales. Results indicate that the caregiving experience is complex. The parents experienced high caregiver's esteem and moderate family support, but also negative impacts on finances and schedule, and to a lesser degree, health. Compared to non-parental caregivers, parental caregivers experienced higher esteem and more impact on finances and schedule.     

Mycophenolate mofetil in stem cell transplant patients in relation to plasma level of active metabolite

OBJECTIVES: To investigate mycophenolate mofetil (MMF) plasma levels and impact on acute graft versus host disease (aGvHD) after stem cell transplantation (SCT).METHODS: SCT patients (n = 14) with aGvHD (>/= II) receiving MMF (1-3 g/d) in addition to cyclosporine, prednisolone, and methotrexate for aGvHD prophylaxis were investigated. Plasma levels of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were determined by high-performance liquid chromatography.RESULTS: Overall median steady state pre-dose plasma MPA concentration was 0.47 mg/L and increased within 75 min after administration to 1.64 mg/L. In comparison to patients with skin aGvHD, patients with gut aGvHD had lower MPA concentrations, both pre-dose (p = 0.16) and after 75 min, (p = 0.02). All 7 patients with skin aGvHD but only 2 patients with gut aGvHD responded to MMF. Overall, the pre-dose plasma MPA concentration was significantly (p = 0.007) greater in responders (n = 9) than in non-responders (n = 5).CONCLUSION: MMF seems to be an effective treatment for aGvHD in SCT patients particular in those patients without gut involvement.     

Successful hematopoietic stem cell collection in patients who fail initial plerixafor mobilization for autologous stem cell transplant

We report our experience of collecting stem cells in patients who failed to mobilize sufficient hematopoietic stem cell (HSC) using plerixafor (P) in the initial mobilization attempt. Twenty four patients were identified who failed a first mobilization attempt using P. Of these, 22 patients received granulocyte colony stimulating factor (G‐CSF) and two patients received cyclophosphamide (CY) + G‐CSF in combination with P for the initial attempt. The agents used for second collection attempt were granulocyte macrophage colony stimulating factor (GM‐CSF) + G‐CSF (19 patients), G‐CSF + P (three patients), CY + G‐CSF (one patient), and bone marrow harvest (one patient). A median of 0.6 × 10⁶ CD34⁺ cells/kg (range 0–1.97) were collected in the initial attempt. A second collection was attempted at a median of 22 days (range 15–127) after the first failed mobilization. The median CD34⁺ cell dose collected with the second attempt was 1.1 × 10⁶ CD34⁺ cells/kg (range 0–7.2). A third collection was attempted in six patients at median of 51 days (range 34–163) after the first failed mobilization. These patients collected a median of 1.1 × 10⁶ CD34⁺ cells/kg (range 0–6.5). Total of 16 patients (67%) collected sufficient cells to undergo autologous stem cell transplant and eight patients (33%) were able to collect ≥2 × 10⁶ CD34⁺ cells/kg in a single subsequent attempt. Our experience suggests that a majority of patients who fail primary mobilization despite use of P can collect sufficient HSC with a subsequent attempt using combination of G‐CSF with either P or GM‐CSF. J. Clin. Apheresis 29:293–298 2014. © 2014 Wiley Periodicals, Inc.     

Defining invasive fungal infections in neutropenic or stem cell transplant patients

Consistent definition of invasive fungal infection is important for managing individual patients, for conducting clinical trials and for evaluating diagnostic tests. However, a recent systematic review of the literature found that at least 25 adverbs have been used to categorize infections and when the criteria in these papers were applied to a single database of patients with fungal infections, there was little agreement. This is the consequence of the varying sensitivity and specificity of different clinical features and investigations in different patient groups and an inconsistency in their application. This review examines the clinical presentation of invasive fungal infections in neutropenic patients and those receiving stem cell transplants, as well as the performance of currently available investigations, in order to consider their value as invasive fungal infection criteria. The recent publication of the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions has provided an international standard for the performance of clinical research in this group of patients. The definitions committee has now been reconvened to consider some of the criticisms of the original criteria and these are likely to evolve further in the future.     

Psychosocial adjustment of adolescent siblings of hematopoietic stem cell transplant patients.

Hematopoietic stem cell transplantation (HSCT) is a widely practiced therapy for many life-threatening childhood disorders. The authors investigated the psychosocial effects of HSCT on siblings of pediatric HSCT patients (n = 44; 21 donors, 23 nondonors, ages 6 to 18 years). Donor siblings reported significantly more anxiety and lower self-esteem than did nondonors. Nondonors showed significantly more school problems. Approximately one third of all siblings reported moderate to severe posttraumatic stress. The study drew on the developmental theory of Erik Erikson and the psychosocial model of posttraumatic stress. As part of the study, the authors used the Measures of Psychosocial Development (MPD), a self-report measure based on Eriksonian constructs. The MPD was used to assess the psychosocial adjustment of 12 siblings who were adolescents (> or =13 years) at the time the study was conducted. In this article, findings are presented from the MPD as well as salient findings from the larger study.     

Clostridium difficile infection in cancer patients and hematopoietic stem cell transplant recipients

Clostridium difficile has become the most common bacterial cause of nosocomial diarrhea. High rates of C. difficile infection (CDI) coupled with increasing morbidity and mortality attributed to CDI have sparked a renewed interest in this disease. Emergence of hypervirulent strains, rising rates of severe and recurrent infection and associated infection control challenges, and diagnostic and therapeutic dilemmas are major issues in the non-oncology population. Scant data on CDI exist in the cancer/transplant population. The purpose of this article is to describe the epidemiology, pathogenesis and management of CDI in patients receiving cancer chemotherapeutic agents, and in hematopoietic stem cell transplant recipients.